Piecewise exponential survival times and analysis of case-cohort data.

PubMed

Li, Yan; Gail, Mitchell H; Preston, Dale L; Graubard, Barry I; Lubin, Jay H

2012-06-15

Case-cohort designs select a random sample of a cohort to be used as control with cases arising from the follow-up of the cohort. Analyses of case-cohort studies with time-varying exposures that use Cox partial likelihood methods can be computer intensive. We propose a piecewise-exponential approach where Poisson regression model parameters are estimated from a pseudolikelihood and the corresponding variances are derived by applying Taylor linearization methods that are used in survey research. The proposed approach is evaluated using Monte Carlo simulations. An illustration is provided using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case-cohort study of serum glucose level and pancreatic cancer was analyzed. Copyright © 2012 John Wiley & Sons, Ltd.

Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

PubMed

Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

2012-06-01

Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

Cryopreserved human amniotic membrane injection for plantar fasciitis: a randomized, controlled, double-blind pilot study.

PubMed

Hanselman, Andrew E; Tidwell, John E; Santrock, Robert D

2015-02-01

Treatment options for plantar fasciitis have resulted in varied patient outcomes. The aim of this study was to compare a novel treatment, cryopreserved human amniotic membrane (c-hAM), to a traditional treatment, corticosteroid. Our hypothesis was that c-hAM would be safe and comparable to corticosteroids for plantar fasciitis in regard to patient outcomes. A randomized, controlled, double-blind, single-center pilot study was completed. Patients were randomized into one of 2 treatment groups: c-hAM or corticosteroid. Patients received an injection at their initial baseline visit with an option for a second injection at their first 6-week follow-up. Total follow-up was obtained for 12 weeks after the most recent injection. The primary outcome measurement was the Foot Health Status Questionnaire (FHSQ). The secondary outcome measurements were the Visual Analog Scale (VAS) and verbally reported percentage improvement. Data were analyzed between groups for the 2 different cohorts (1 injection versus 2 injections). Twenty-three patients had complete follow-up. Fourteen were randomized to receive corticosteroid and 9 were randomized to receive c-hAM. Three patients in each group received second injections. With the numbers available, the majority of outcome measurements showed no statistical difference between groups. The corticosteroid did, however, have greater FHSQ shoe fit improvement (P = .0244) at 6 weeks, FHSQ general health improvement (P = .0132) at 6 weeks, and verbally reported improvement (P = .041) at 12 weeks in the one-injection cohort. Cryopreserved hAM had greater FHSQ foot pain improvement (P = .0113) at 18 weeks in the 2-injection cohort. Cryopreserved hAM injection may be safe and comparable to corticosteroid injection for treatment of plantar fasciitis. This is a pilot study and requires further investigation. Level I, prospective randomized trial. © The Author(s) 2014.

Methodology Series Module 1: Cohort Studies

PubMed Central

Setia, Maninder Singh

2016-01-01

Cohort design is a type of nonexperimental or observational study design. In a cohort study, the participants do not have the outcome of interest to begin with. They are selected based on the exposure status of the individual. They are then followed over time to evaluate for the occurrence of the outcome of interest. Some examples of cohort studies are (1) Framingham Cohort study, (2) Swiss HIV Cohort study, and (3) The Danish Cohort study of psoriasis and depression. These studies may be prospective, retrospective, or a combination of both of these types. Since at the time of entry into the cohort study, the individuals do not have outcome, the temporality between exposure and outcome is well defined in a cohort design. If the exposure is rare, then a cohort design is an efficient method to study the relation between exposure and outcomes. A retrospective cohort study can be completed fast and is relatively inexpensive compared with a prospective cohort study. Follow-up of the study participants is very important in a cohort study, and losses are an important source of bias in these types of studies. These studies are used to estimate the cumulative incidence and incidence rate. One of the main strengths of a cohort study is the longitudinal nature of the data. Some of the variables in the data will be time-varying and some may be time independent. Thus, advanced modeling techniques (such as fixed and random effects models) are useful in analysis of these studies. PMID:26955090

Methodology Series Module 1: Cohort Studies.

PubMed

Setia, Maninder Singh

2016-01-01

Cohort design is a type of nonexperimental or observational study design. In a cohort study, the participants do not have the outcome of interest to begin with. They are selected based on the exposure status of the individual. They are then followed over time to evaluate for the occurrence of the outcome of interest. Some examples of cohort studies are (1) Framingham Cohort study, (2) Swiss HIV Cohort study, and (3) The Danish Cohort study of psoriasis and depression. These studies may be prospective, retrospective, or a combination of both of these types. Since at the time of entry into the cohort study, the individuals do not have outcome, the temporality between exposure and outcome is well defined in a cohort design. If the exposure is rare, then a cohort design is an efficient method to study the relation between exposure and outcomes. A retrospective cohort study can be completed fast and is relatively inexpensive compared with a prospective cohort study. Follow-up of the study participants is very important in a cohort study, and losses are an important source of bias in these types of studies. These studies are used to estimate the cumulative incidence and incidence rate. One of the main strengths of a cohort study is the longitudinal nature of the data. Some of the variables in the data will be time-varying and some may be time independent. Thus, advanced modeling techniques (such as fixed and random effects models) are useful in analysis of these studies.

Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis.

PubMed

Sheth, Ujash; Simunovic, Nicole; Klein, Guy; Fu, Freddie; Einhorn, Thomas A; Schemitsch, Emil; Ayeni, Olufemi R; Bhandari, Mohit

2012-02-15

The recent emergence of autologous blood concentrates, such as platelet-rich plasma, as a treatment option for patients with orthopaedic injuries has led to an extensive debate about their clinical benefit. We conducted a systematic review and meta-analysis to determine the efficacy of autologous blood concentrates in decreasing pain and improving healing and function in patients with orthopaedic bone and soft-tissue injuries. We searched MEDLINE and Embase for randomized controlled trials or prospective cohort studies that compared autologous blood concentrates with a control therapy in patients with an orthopaedic injury. We identified additional studies by searching through the bibliographies of eligible studies as well as the archives of orthopaedic conferences and meetings. Twenty-three randomized trials and ten prospective cohort studies were identified. There was a lack of consistency in outcome measures across all studies. In six randomized controlled trials (n = 358) and three prospective cohort studies (n = 88), the authors reported visual analog scale (VAS) scores when comparing platelet-rich plasma with a control therapy across injuries to the acromion, rotator cuff, lateral humeral epicondyle, anterior cruciate ligament, patella, tibia, and spine. The use of platelet-rich plasma provided no significant benefit up to (and including) twenty-four months across the randomized trials (standardized mean difference, -0.34; 95% confidence interval [CI], -0.75 to 0.06) or the prospective cohort studies (standardized mean difference, -0.20; 95% CI, -0.64 to 0.23). Both point estimates suggested a small trend favoring platelet-rich plasma, but the associated wide confidence intervals were consistent with nonsignificant effects. The current literature is complicated by a lack of standardization of study protocols, platelet-separation techniques, and outcome measures. As a result, there is uncertainty about the evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries.

A Randomized Controlled Trial of Short and Standard-Length Consent Forms for a Genetic Cohort Study: Is Longer Better?

PubMed Central

Matsui, Kenji; Lie, Reidar K.; Turin, Tanvir C.; Kita, Yoshikuni

2012-01-01

Background Although the amount of detail in informed consent documents has increased over time and the documents have therefore become very long, there is little research on whether longer informed consent documents actually result in (1) better informed research subjects or (2) higher consent rates. We therefore conducted an add-on randomized controlled trial to the Takashima Study, a prospective Japanese population-based genetic cohort study, to test the hypothesis that a shorter informed consent form would satisfy both of the above goals. Methods Standard (10 459 words, 11 pages) and short (3602 words, 5 pages) consent forms in Japanese were developed and distributed using cluster-randomization to 293 potential cohort subjects living in 9 medico-social units and 288 subjects in 8 medico-social units, respectively. Results Few differences were found between the 2 groups with regard to outcome measures, including participants’ self-perceived understanding, recall of information, concerns, voluntariness, trust, satisfaction, sense of duty, and consent rates. Conclusions A short informed consent form was no less valid than a standard form with regard to fulfilling ethical requirements and securing the scientific validity of research. PMID:22447213

Is there a role for e-cigarettes in smoking cessation?

PubMed

Leduc, Charlotte; Quoix, Elisabeth

2016-04-01

The use of e-cigarettes has dramatically increased over the past few years and their role in smoking cessation remains controversial. Several clinical studies have evaluated their efficacy in smoking cessation but most of them are prospective cohort studies. Only two randomized, controlled trials have compared e-cigarettes versus placebo or patches. A meta-analysis of these two randomized, controlled trials has been performed. Nicotine-containing e-cigarettes appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo. However, these results are rated 'low' by GRADE standards. Many cohort studies have been conducted, with contradictory results. For some, e-cigarettes could increase the risk of nonsmokers developing nicotine dependence and of current smokers maintaining their dependence. The debate remains open and more randomized trials are needed with long-term data about the efficacy and safety of e-cigarettes. © The Author(s), 2015.

Responsiveness-informed multiple imputation and inverse probability-weighting in cohort studies with missing data that are non-monotone or not missing at random.

PubMed

Doidge, James C

2018-02-01

Population-based cohort studies are invaluable to health research because of the breadth of data collection over time, and the representativeness of their samples. However, they are especially prone to missing data, which can compromise the validity of analyses when data are not missing at random. Having many waves of data collection presents opportunity for participants' responsiveness to be observed over time, which may be informative about missing data mechanisms and thus useful as an auxiliary variable. Modern approaches to handling missing data such as multiple imputation and maximum likelihood can be difficult to implement with the large numbers of auxiliary variables and large amounts of non-monotone missing data that occur in cohort studies. Inverse probability-weighting can be easier to implement but conventional wisdom has stated that it cannot be applied to non-monotone missing data. This paper describes two methods of applying inverse probability-weighting to non-monotone missing data, and explores the potential value of including measures of responsiveness in either inverse probability-weighting or multiple imputation. Simulation studies are used to compare methods and demonstrate that responsiveness in longitudinal studies can be used to mitigate bias induced by missing data, even when data are not missing at random.

Supplemental Reading Strategy Instruction for Adolescents: A Randomized Trial and Follow-up Study

ERIC Educational Resources Information Center

Cantrell, Susan Chambers; Almasi, Janice F.; Rintamaa, Margaret; Carter, Janis C.

2016-01-01

In this study, the authors examine the impact of a yearlong supplemental reading course involving daily instruction in the learning strategies curriculum on lower achieving adolescent students' reading achievement and motivation. Using a multiple-cohort randomized treatment-control group design over 4 years, they compared achievement and…

Indirect language therapy for children with persistent language impairment in mainstream primary schools: outcomes from a cohort intervention.

PubMed

McCartney, Elspeth; Boyle, James; Ellis, Sue; Bannatyne, Susan; Turnbull, Mary

2011-01-01

A manualized language therapy developed via a randomized controlled trial had proved efficacious in the short-term in developing expressive language for mainstream primary school children with persistent language impairment. This therapy had been delivered to a predetermined schedule by speech and language therapists or speech and language therapy assistants to children individually or in groups. However, this model of service delivery is no longer the most common model in UK schools, where indirect consultancy approaches with intervention delivered by school staff are often used. A cohort study was undertaken to investigate whether the therapy was equally efficacious when delivered to comparable children by school staff, rather than speech and language therapists or speech and language therapy assistants. Children in the cohort study were selected using the same criteria as in the randomized controlled trial, and the same manualized therapy was used, but delivered by mainstream school staff using a consultancy model common in the UK. Outcomes were compared with those of randomized controlled trial participants. The gains in expressive language measured in the randomized controlled trial were not replicated in the cohort study. Less language-learning activity was recorded than had been planned, and less than was delivered in the randomized controlled trial. Implications for 'consultancy' speech and language therapist service delivery models in mainstream schools are outlined. At present, the more efficacious therapy is that delivered by speech and language therapists or speech and language therapy assistants to children individually or in groups. This may be related to more faithful adherence to the interventions schedule, and to a probably greater amount of language-learning activity undertaken. Intervention delivered via school-based 'consultancy' approaches in schools will require to be carefully monitored by schools and SLT services. © 2010 Royal College of Speech & Language Therapists.

Assessing different measures of population-level vaccine protection using a case-control study.

PubMed

Ali, Mohammad; You, Young Ae; Kanungo, Suman; Manna, Byomkesh; Deen, Jacqueline L; Lopez, Anna Lena; Wierzba, Thomas F; Bhattacharya, Sujit K; Sur, Dipika; Clemens, John D

2015-11-27

Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects. 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case-control analyses. The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection. Copyright © 2015. Published by Elsevier Ltd.

Evaluation of a Nationwide Pharmacist-Led Phone Outreach Program to Improve Osteoporosis Management in Older Women with Recently Sustained Fractures.

PubMed

Tso, Luke S; Loi, Danmy; Mosley, David G; Yi, David; Stockl, Karen M; Lew, Heidi C; Solow, Brian K

2015-09-01

Osteoporosis-related fractures are a considerable economic burden on the U.S. health care system. Since 2008, the Centers for Medicare Medicaid Services have adopted a Medicare Part C Five-Star Quality Rating measure to ensure that a woman's previously unaddressed osteoporosis is managed appropriately after a fracture. Despite the effort to improve this gap in care, the 2013 CMS plan ratings fact sheet reported an average star rating of 1.4 stars for the osteoporosis measure, the lowest score for any measure across all health plans. To evaluate the impact of conducting a pharmacist-led, telephone outreach program to members or their providers to improve osteoporosis management in elderly women after experiencing fractures.  This was a prospective, randomized study to evaluate the effectiveness of 3 different intervention strategies within a nationwide managed care population. Women aged 66 years and older who experienced a new bone fracture between January 1, 2012-August 31, 2012, were identified through medical claims. Women who were treated with an osteoporosis medication or received a bone mineral density (BMD) test within a year of their fractures were excluded. Study patients were randomized into 3 intervention cohorts: (1) baseline intervention consisting of member educational mailing and provider educational mail or fax notification; (2) baseline intervention plus a live outbound intervention call to members by a pharmacist; and (3) baseline intervention plus a pharmacist call to members' providers to recommend starting osteoporosis therapy and/or a bone mineral density (BMD) test. An intent-to-treat and per protocol analyses were employed, and appropriate osteoporosis management (initiation of osteoporosis therapy and/or BMD testing) 120 days after the baseline intervention and 180 days after a fracture were measured. The study identified 6,591 members who were equally randomized into 3 cohorts. The baseline demographics in each cohort were similar. Results of the intent-to-treat analysis showed more members in cohort 3 receiving appropriate osteoporosis management (13.0%) compared with those in cohort 2 (10.3%, P  less than  0.005) or compared with those in cohort 1 (9.1%, P  less than  0.001). No difference was detected between those receiving additional member calls (cohort 2) and those receiving only the baseline intervention (cohort 1). Similar results were observed utilizing the 180 days after fracture time frame.  The effectiveness of a pharmacist-led telephone intervention directed at providers or members was examined in this randomized study. Pharmacist calls to members did not improve osteoporosis management over member and provider mail and fax notifications. Greater impact was demonstrated by performing a pharmacist call intervention with providers rather than with members.

Safety, Tolerability, and Pharmacokinetics of Therapeutic and Supratherapeutic Doses of Tramadol Hydrochloride in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Multiple-Ascending-Dose Study.

PubMed

DeLemos, Byron; Richards, Henry M; Vandenbossche, Joris; Ariyawansa, Jay; Natarajan, Jaya; Alexander, Binu; Ramakrishna, Tage; Murtaugh, Thomas; Stahlberg, Hans-Jürgen

2017-11-01

This randomized, double-blind, parallel-group multiple-ascending-dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91.7%) completed the study. The AUC tau,ss of tramadol increased approximately 2.2- and 3.6-fold for the (+) enantiomer and 2.0- and 3.5-fold for the (-) enantiomer with increasing dose from 200 to 400  and 600 mg/day, whereas the C max,ss increased 2.1- and 3.3-fold for the (+) enantiomer and 2.0- and 3.2-fold for the (-) enantiomer. Overall, 21 participants (87.5%) participants reported ≥1 treatment-emergent adverse event; most frequent were nausea (17 of 24, 70.8%) and vomiting (7 of 24, 29.2%). Vomiting (affected participants and events) increased with increasing dose from 200 to 600 mg/day but was mild (5 of 24) or moderate (2 of 24) in severity. All tested dosage regimens of tramadol showed acceptable safety and tolerability profile for further investigation in a thorough QT/QTc study. © 2017, The American College of Clinical Pharmacology.

Impact of the Good Behavior Game, a Universal Classroom–Based Behavior Intervention, on Young Adult Service Use for Problems with Emotions, Behavior, or Drugs or Alcohol

PubMed Central

Poduska, Jeanne; Kellam, Sheppard; Wang, Wei; Brown, C. Hendricks; Ialongo, Nicholas; Toyinbo, Peter

2009-01-01

Background The Good Behavior Game (GBG) is a classroom behavior management strategy focused on socializing children to the role of student and aimed at reducing early aggressive, disruptive behavior, a confirmed antecedent to service use. The GBG was tested in a randomized field trial in 19 elementary schools in two cohorts of children as they attended first and second grades. This article reports on the impact of the GBG on service use through young adulthood. Methods Three or four schools in each of five urban areas were matched and randomly assigned to one of three conditions: 1) GBG, 2) an intervention aimed at academic achievement, or 3) the standard program of the school system. Children were assigned to classrooms to ensure balance, and teachers and classrooms were randomly assigned to intervention conditions. Results This study provides evidence of a positive impact of a universal preventive intervention on later service use by males, although not by females, for problems with emotions, behavior, or drugs or alcohol. For both cohorts, males in GBG classrooms who had been rated as highly aggressive, disruptive by their teachers in the fall of first grade had a lower rate of school-based service use than their counterparts in control classrooms. Replication The design employed two cohorts of students. Although both first- and second-grade teachers received less training and support with the second cohorts of students than with the first cohort, the impact of GBG was similar across both cohorts. PMID:18249508

Correction of confounding bias in non-randomized studies by appropriate weighting.

PubMed

Schmoor, Claudia; Gall, Christine; Stampf, Susanne; Graf, Erika

2011-03-01

In non-randomized studies, the assessment of a causal effect of treatment or exposure on outcome is hampered by possible confounding. Applying multiple regression models including the effects of treatment and covariates on outcome is the well-known classical approach to adjust for confounding. In recent years other approaches have been promoted. One of them is based on the propensity score and considers the effect of possible confounders on treatment as a relevant criterion for adjustment. Another proposal is based on using an instrumental variable. Here inference relies on a factor, the instrument, which affects treatment but is thought to be otherwise unrelated to outcome, so that it mimics randomization. Each of these approaches can basically be interpreted as a simple reweighting scheme, designed to address confounding. The procedures will be compared with respect to their fundamental properties, namely, which bias they aim to eliminate, which effect they aim to estimate, and which parameter is modelled. We will expand our overview of methods for analysis of non-randomized studies to methods for analysis of randomized controlled trials and show that analyses of both study types may target different effects and different parameters. The considerations will be illustrated using a breast cancer study with a so-called Comprehensive Cohort Study design, including a randomized controlled trial and a non-randomized study in the same patient population as sub-cohorts. This design offers ideal opportunities to discuss and illustrate the properties of the different approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence function based variance estimation and missing data issues in case-cohort studies.

PubMed

Mark, S D; Katki, H

2001-12-01

Recognizing that the efficiency in relative risk estimation for the Cox proportional hazards model is largely constrained by the total number of cases, Prentice (1986) proposed the case-cohort design in which covariates are measured on all cases and on a random sample of the cohort. Subsequent to Prentice, other methods of estimation and sampling have been proposed for these designs. We formalize an approach to variance estimation suggested by Barlow (1994), and derive a robust variance estimator based on the influence function. We consider the applicability of the variance estimator to all the proposed case-cohort estimators, and derive the influence function when known sampling probabilities in the estimators are replaced by observed sampling fractions. We discuss the modifications required when cases are missing covariate information. The missingness may occur by chance, and be completely at random; or may occur as part of the sampling design, and depend upon other observed covariates. We provide an adaptation of S-plus code that allows estimating influence function variances in the presence of such missing covariates. Using examples from our current case-cohort studies on esophageal and gastric cancer, we illustrate how our results our useful in solving design and analytic issues that arise in practice.

Evaluation of a Short-term, Cognitive-Behavioral Intervention for Primary Age Children with Anger-Related Difficulties

ERIC Educational Resources Information Center

Cole, Rachel L.; Treadwell, Susanne; Dosani, Sima; Frederickson, Norah

2013-01-01

This study evaluated the school-based short-term, cognitive-behavioral group anger management programme, "Learning How to Deal with our Angry Feelings" (Southampton Psychology Service, 2003). Thirteen groups of children aged 7- to 11-years-old were randomly allocated to two different cohorts: One cohort ("n"?=?35) first…

Use of Peritoneal Dialysis in AKI: A Systematic Review

PubMed Central

Chionh, Chang Yin; Soni, Sachin S.; Finkelstein, Fredric O.; Ronco, Claudio

2013-01-01

Summary Background and objectives The role of peritoneal dialysis in the management of AKI is not well defined, although it remains frequently used, especially in low-resource settings. A systematic review was performed to describe outcomes in AKI treated with peritoneal dialysis and compare peritoneal dialysis with extracorporeal blood purification, such as continuous or intermittent hemodialysis. Design, setting, participants, & measurements MEDLINE, CINAHL, and Central Register of Controlled Trials were searched in July of 2012. Eligible studies selected were observational cohort or randomized adult population studies on peritoneal dialysis in the setting of AKI. The primary outcome of interest was all-cause mortality. Summary estimates of odds ratio were obtained using a random effects model. Results Of 982 citations, 24 studies (n=1556 patients) were identified. The overall methodological quality was low. Thirteen studies described patients (n=597) treated with peritoneal dialysis only; pooled mortality was 39.3%. In 11 studies (7 cohort studies and 4 randomized trials), patients received peritoneal dialysis (n=392, pooled mortality=58.0%) or extracorporeal blood purification (n=567, pooled mortality=56.1%). In the cohort studies, there was no difference in mortality between peritoneal dialysis and extracorporeal blood purification (odds ratio, 0.96; 95% confidence interval, 0.53 to 1.71). In four randomized trials, there was also no difference in mortality (odds ratio, 1.50; 95% confidence interval, 0.46 to 4.86); however, heterogeneity was significant (I2=73%, P=0.03). Conclusions There is currently no evidence to suggest significant differences in mortality between peritoneal dialysis and extracorporeal blood purification in AKI. There is a need for good-quality evidence in this important area. PMID:23833316

A comparison of the results of prospective and retrospective cohort studies in the field of digestive surgery.

PubMed

Ukai, Tomohiko; Shikata, Satoru; Nakayama, Takeo; Takemura, Yousuke C

2017-07-01

We compared the results of prospective and retrospective cohort studies in the field of digestive surgery to clarify whether the results of prospective cohort studies were more similar to those of randomized controlled trials (RCTs). We conducted a secondary analysis of the results to compare the results of RCTs with those of cohort studies in meta-analyses of 18 digestive surgical topics. The data from the prospective and retrospective cohort studies were combined. The summary estimates of each design were compared with those of RCTs. We used the Z score to investigate discrepancies. Twenty-nine outcomes of 11 topics were investigated in 289 cohort studies (prospective, n = 69; retrospective, n = 220). These were compared with the outcomes of 123 RCTs. In comparison to retrospective studies, the summary estimates of the prospective cohort studies were more similar to those of the RCTs [19/29 (prospective) vs. 10/29 (retrospective), P = 0.035). Five of the 29 outcomes of prospective studies and 6 of 29 outcomes of retrospective studies (P = 0.99) showed significant discrepancies in comparison to RCTs. In the digestive surgical field, the results of prospective cohort studies tended to be more similar to those of RCTs than retrospective studies; however, there were no significant discrepancies between the two types of cohort study.

Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study.

PubMed

Solin, Lawrence J; Gray, Robert; Hughes, Lorie L; Wood, William C; Lowen, Mary Ann; Badve, Sunil S; Baehner, Frederick L; Ingle, James N; Perez, Edith A; Recht, Abram; Sparano, Joseph A; Davidson, Nancy E

2015-11-20

To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians. © 2015 by American Society of Clinical Oncology.

Longitudinal analysis of the strengths and difficulties questionnaire scores of the Millennium Cohort Study children in England using M-quantile random-effects regression.

PubMed

Tzavidis, Nikos; Salvati, Nicola; Schmid, Timo; Flouri, Eirini; Midouhas, Emily

2016-02-01

Multilevel modelling is a popular approach for longitudinal data analysis. Statistical models conventionally target a parameter at the centre of a distribution. However, when the distribution of the data is asymmetric, modelling other location parameters, e.g. percentiles, may be more informative. We present a new approach, M -quantile random-effects regression, for modelling multilevel data. The proposed method is used for modelling location parameters of the distribution of the strengths and difficulties questionnaire scores of children in England who participate in the Millennium Cohort Study. Quantile mixed models are also considered. The analyses offer insights to child psychologists about the differential effects of risk factors on children's outcomes.

Designing clinical trials for amblyopia

PubMed Central

Holmes, Jonathan M.

2015-01-01

Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. PMID:25752747

Laparoscopic skills acquisition: a study of simulation and traditional training.

PubMed

Marlow, Nicholas; Altree, Meryl; Babidge, Wendy; Field, John; Hewett, Peter; Maddern, Guy J

2014-12-01

Training in basic laparoscopic skills can be undertaken using traditional methods, where trainees are educated by experienced surgeons through a process of graduated responsibility or by simulation-based training. This study aimed to assess whether simulation trained individuals reach the same level of proficiency in basic laparoscopic skills as traditional trained participants when assessed in a simulated environment. A prospective study was undertaken. Participants were allocated to one of two cohorts according to surgical experience. Participants from the inexperienced cohort were randomized to receive training in basic laparoscopic skills on either a box trainer or a virtual reality simulator. They were then assessed on the simulator on which they did not receive training. Participants from the experienced cohort, considered to have received traditional training in basic laparoscopic skills, did not receive simulation training and were randomized to either the box trainer or virtual reality simulator for skills assessment. The assessment scores from different cohorts on either simulator were then compared. A total of 138 participants completed the assessment session, 101 in the inexperienced simulation-trained cohort and 37 on the experienced traditionally trained cohort. There was no statistically significant difference between the training outcomes of simulation and traditionally trained participants, irrespective of the simulator type used. The results demonstrated that participants trained on either a box trainer or virtual reality simulator achieved a level of basic laparoscopic skills assessed in a simulated environment that was not significantly different from participants who had been traditionally trained in basic laparoscopic skills. © 2013 Royal Australasian College of Surgeons.

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

PubMed

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1-state)--a prospective multicenter randomized controlled clinical trial using a comprehensive cohort design.

PubMed

Moergel, Maximilian; Jahn-Eimermacher, Antje; Krummenauer, Frank; Reichert, Torsten E; Wagner, Wilfried; Wendt, Thomas G; Werner, Jochen A; Al-Nawas, Bilal

2009-12-23

Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation. The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome. The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study. ClinicalTrials.gov: NCT00964977.

Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis.

PubMed

Janmaat, Cynthia J; van Diepen, Merel; van Hagen, Cheyenne Ce; Rotmans, Joris I; Dekker, Friedo W; Dekkers, Olaf M

2018-01-01

Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3-5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3-5 patients, in these two different study types. We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline (mL/min/1.73 m 2 ) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. We included 60 studies (43 CKD 3-5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m 2 in CKD 3-5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3-5 cohorts. Thus, eGFR decline data from CKD 3-5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome.

Accelerated longitudinal designs: An overview of modelling, power, costs and handling missing data.

PubMed

Galbraith, Sally; Bowden, Jack; Mander, Adrian

2017-02-01

Longitudinal studies are often used to investigate age-related developmental change. Whereas a single cohort design takes a group of individuals at the same initial age and follows them over time, an accelerated longitudinal design takes multiple single cohorts, each one starting at a different age. The main advantage of an accelerated longitudinal design is its ability to span the age range of interest in a shorter period of time than would be possible with a single cohort longitudinal design. This paper considers design issues for accelerated longitudinal studies. A linear mixed effect model is considered to describe the responses over age with random effects for intercept and slope parameters. Random and fixed cohort effects are used to cope with the potential bias accelerated longitudinal designs have due to multiple cohorts. The impact of other factors such as costs and the impact of dropouts on the power of testing or the precision of estimating parameters are examined. As duration-related costs increase relative to recruitment costs the best designs shift towards shorter duration and eventually cross-sectional design being best. For designs with the same duration but differing interval between measurements, we found there was a cutoff point for measurement costs relative to recruitment costs relating to frequency of measurements. Under our model of 30% dropout there was a maximum power loss of 7%.

Coaching and Demonstration of Evidence-Based Book-Reading Practices: Effects on Head Start Teachers' Literacy-Related Behaviors and Classroom Environment

ERIC Educational Resources Information Center

Gettinger, Maribeth; Stoiber, Karen C.

2016-01-01

This study examined the effects of coaching with versus without demonstrations of evidence-based book-reading practices on teachers' use of strategies during independent book-reading periods. A total of 22 Head Start teachers were randomly assigned to one of two cohorts. One cohort (n = 12) participated in biweekly coaching sessions that included…

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

Tsinovoi, Cari L; Xun, Pengcheng; McClure, Leslie A; Carioni, Vivian M O; Brockman, John D; Cai, Jianwen; Guallar, Eliseo; Cushman, Mary; Unverzagt, Frederick W; Howard, Virginia J; He, Ka

2018-01-01

The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research. © 2017 American Heart Association, Inc.

Comparison of Long-term Differences in Dysphagia: Cervical Arthroplasty and Anterior Cervical Fusion.

PubMed

Smucker, Joseph D; Bassuener, Scott R; Sasso, Rick C; Riew, K Daniel

2017-10-01

Retrospective cohort study. This study investigates the incidence of long-term dysphagia in cervical disc arthroplasty, and anterior cervical discectomy and fusion (ACDF) patients. No long-term comparison of dysphagia between cervical arthroplasty and fusion patients has been published. Widely variable short-term postsurgical dysphagia rates have been reported. Cohorts for this study are patients with single-level cervical degenerative disc disease previously enrolled in a randomized clinical trial comparing cervical arthroplasty and ACDF. Subjective modified Bazaz Dysphagia Severity questionnaires were distributed to each patient at a minimum of 5 years postoperative for the long-term assessment. Dysphagia severity data were pooled to compare the rate of patients with dysphagia (grade>1) to asymptomatic (grade=1). In the arthroplasty cohort, 15 of 22 (68%) patients completed long-term swallowing questionnaires with no reports of dysphagia. Eighteen of 25 (72%) ACDF patients completed questionnaires, with 5 of 18 (28%) reporting dysphagia. This is a statistically significant difference (P=0.042) favoring lower rates of long-term dysphagia after cervical arthroplasty at an average interval of 7 years postoperative (range, 5.5-8.5 y). No significant difference between rates of self-reported short-term dysphagia was noted with 12% (3/25) and 9% (2/22) in the ACDF and arthroplasty groups, respectively (P=0.56). All short-term dysphagia cases in the arthroplasty cohort reported complete resolution of symptoms within 12 months postoperative. In the ACDF cohort, persistent symptoms at 7 years were noted in all responding patients. Three ACDF patients reported new late-onset, which was not noted in the arthroplasty cohort. To date, these findings represent the longest reported follow-up interval comparing rates of dysphagia between randomized cohorts of cervical arthroplasty and fusion patients. Our study suggests that cervical arthroplasty is less likely than ACDF to cause sustained long-term or late-presenting dysphagia.

Diagnosing gestational diabetes mellitus in the Danish National Birth Cohort.

PubMed

Olsen, Sjurdur F; Houshmand-Oeregaard, Azedeh; Granström, Charlotta; Langhoff-Roos, Jens; Damm, Peter; Bech, Bodil H; Vaag, Allan A; Zhang, Cuilin

2017-05-01

The Danish National Birth Cohort (DNBC) contains comprehensive information on diet, lifestyle, constitutional and other major characteristics of women during pregnancy. It provides a unique source for studies on health consequences of gestational diabetes mellitus. Our aim was to identify and validate the gestational diabetes mellitus cases in the cohort. We extracted clinical information from hospital records for 1609 pregnancies included in the Danish National Birth Cohort with a diagnosis of diabetes during or before pregnancy registered in the Danish National Patient Register and/or from a Danish National Birth Cohort interview during pregnancy. We further validated the diagnosis of gestational diabetes mellitus in 2126 randomly selected pregnancies from the entire Danish National Birth Cohort. From the individual hospital records, an expert panel evaluated gestational diabetes mellitus status based on results from oral glucose tolerance tests, fasting blood glucose and Hb1c values, as well as diagnoses made by local obstetricians. The audit categorized 783 pregnancies as gestational diabetes mellitus, corresponding to 0.89% of the 87 792 pregnancies for which a pregnancy interview for self-reported diabetes in pregnancy was available. From the randomly selected group the combined information from register and interviews could correctly identify 96% (95% CI 80-99.9%) of all cases in the entire Danish National Birth Cohort population. Positive predictive value, however, was only 59% (56-61%). The combined use of data from register and interview provided a high sensitivity for gestational diabetes mellitus diagnosis. The low positive predictive value, however, suggests that systematic validation by hospital record review is essential not to underestimate the health consequences of gestational diabetes mellitus in future studies. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

[Laservaporization of the prostate: current status of the greenlight and diode laser].

PubMed

Rieken, M; Bachmann, A; Gratzke, C

2013-03-01

In the last decade laser vaporization of the prostate has emerged as a safe and effective alternative to transurethral resection of the prostate (TURP). This was facilitated in particular by the introduction of photoselective vaporization of the prostate (PVP) with a 532 nm 80 W KTP laser in 2002. Prospective randomized trials comparing PVP and TURP with a maximum follow-up of 3 years mostly demonstrated comparable functional results. Cohort studies showed a safe application of PVP in patients under oral anticoagulation and with large prostates. Systems from various manufacturers with different maximum power output and wavelengths are now available for diode laser vaporization of the prostate. Prospective randomized trials comparing diode lasers and TURP are not yet available. In cohort studies and comparative studies PVP diode lasers are characterized by excellent hemostatic properties but functional results vary greatly with some studies reporting high reoperation rates.

Perspective: NutriGrade: A Scoring System to Assess and Judge the Meta-Evidence of Randomized Controlled Trials and Cohort Studies in Nutrition Research.

PubMed

Schwingshackl, Lukas; Knüppel, Sven; Schwedhelm, Carolina; Hoffmann, Georg; Missbach, Benjamin; Stelmach-Mardas, Marta; Dietrich, Stefan; Eichelmann, Fabian; Kontopantelis, Evangelos; Iqbal, Khalid; Aleksandrova, Krasimira; Lorkowski, Stefan; Leitzmann, Michael F; Kroke, Anja; Boeing, Heiner

2016-11-01

The objective of this study was to develop a scoring system (NutriGrade) to evaluate the quality of evidence of randomized controlled trial (RCT) and cohort study meta-analyses in nutrition research, building upon previous tools and expert recommendations. NutriGrade aims to assess the meta-evidence of an association or effect between different nutrition factors and outcomes, taking into account nutrition research-specific requirements not considered by other tools. In a pretest study, 6 randomly selected meta-analyses investigating diet-disease relations were evaluated with NutriGrade by 5 independent raters. After revision, NutriGrade was applied by the same raters to 30 randomly selected meta-analyses in the same thematic area. The reliability of ratings of NutriGrade items was calculated with the use of a multirater κ, and reliability of the total (summed scores) was calculated with the use of intraclass correlation coefficients (ICCs). The following categories for meta-evidence evaluation were established: high (8-10), moderate (6-7.99), low (4-5.99), and very low (0-3.99). The NutriGrade scoring system (maximum of 10 points) comprises the following items: 1) risk of bias, study quality, and study limitations, 2) precision, 3) heterogeneity, 4) directness, 5) publication bias, 6) funding bias, 7) study design, 8) effect size, and 9) dose-response. The NutriGrade score varied between 2.9 (very low meta-evidence) and 8.8 (high meta-evidence) for meta-analyses of RCTs, and it ranged between 3.1 and 8.8 for meta-analyses of cohort studies. The κ value of the ratings for each scoring item varied from 0.32 (95% CI: 0.22, 0.42) for risk of bias for cohort studies and 0.95 (95% CI: 0.91, 0.99) for study design, with a mean κ of 0.66 (95% CI: 0.53, 0.79). The ICC of the total score was 0.81 (95% CI: 0.69, 0.90). The NutriGrade scoring system showed good agreement and reliability. The initial findings regarding the performance of this newly established scoring system need further evaluation in independent analyses. © 2016 American Society for Nutrition.

Perspective: NutriGrade: A Scoring System to Assess and Judge the Meta-Evidence of Randomized Controlled Trials and Cohort Studies in Nutrition Research123

PubMed Central

Knüppel, Sven; Schwedhelm, Carolina; Hoffmann, Georg; Missbach, Benjamin; Stelmach-Mardas, Marta; Dietrich, Stefan; Eichelmann, Fabian; Kontopanteils, Evangelos; Iqbal, Khalid; Aleksandrova, Krasimira; Lorkowski, Stefan; Leitzmann, Michael F; Kroke, Anja; Boeing, Heiner

2016-01-01

The objective of this study was to develop a scoring system (NutriGrade) to evaluate the quality of evidence of randomized controlled trial (RCT) and cohort study meta-analyses in nutrition research, building upon previous tools and expert recommendations. NutriGrade aims to assess the meta-evidence of an association or effect between different nutrition factors and outcomes, taking into account nutrition research–specific requirements not considered by other tools. In a pretest study, 6 randomly selected meta-analyses investigating diet–disease relations were evaluated with NutriGrade by 5 independent raters. After revision, NutriGrade was applied by the same raters to 30 randomly selected meta-analyses in the same thematic area. The reliability of ratings of NutriGrade items was calculated with the use of a multirater κ, and reliability of the total (summed scores) was calculated with the use of intraclass correlation coefficients (ICCs). The following categories for meta-evidence evaluation were established: high (8–10), moderate (6–7.99), low (4–5.99), and very low (0–3.99). The NutriGrade scoring system (maximum of 10 points) comprises the following items: 1) risk of bias, study quality, and study limitations, 2) precision, 3) heterogeneity, 4) directness, 5) publication bias, 6) funding bias, 7) study design, 8) effect size, and 9) dose-response. The NutriGrade score varied between 2.9 (very low meta-evidence) and 8.8 (high meta-evidence) for meta-analyses of RCTs, and it ranged between 3.1 and 8.8 for meta-analyses of cohort studies. The κ value of the ratings for each scoring item varied from 0.32 (95% CI: 0.22, 0.42) for risk of bias for cohort studies and 0.95 (95% CI: 0.91, 0.99) for study design, with a mean κ of 0.66 (95% CI: 0.53, 0.79). The ICC of the total score was 0.81 (95% CI: 0.69, 0.90). The NutriGrade scoring system showed good agreement and reliability. The initial findings regarding the performance of this newly established scoring system need further evaluation in independent analyses. PMID:28140319

Minimally Displaced, Isolated Radial Head and Neck Fractures Do Not Require Formal Physical Therapy: Results of a Prospective Randomized Trial.

PubMed

Egol, Kenneth A; Haglin, Jack M; Lott, Ariana; Fisher, Nina; Konda, Sanjit R

2018-04-18

Nondisplaced and minimally displaced fractures of the radial head and neck are common injuries, yet the role of physical therapy (PT) in their treatment is unclear. The aim of this trial was to assess the need for formal PT following a simple fracture of the radial head or neck. Patients who had a nondisplaced or minimally displaced fracture of the radial head or neck and presented to 1 of 2 providers were enrolled prospectively between January 2014 and August 2016. Patients were randomized to receive outpatient PT or perform self-directed home exercise. The follow-up intervals were 6 weeks, 3 months, 6 months, and at least 1 year. The outcome measures were Disabilities of the Arm, Shoulder and Hand (DASH) scores; pain; time to clinical healing; and range of motion. Demographic data were analyzed using the Mann-Whitney U test and Fisher exact test. Independent-samples t tests were utilized to compare outcome measures. Fifty-one patients were enrolled in the study. The average follow-up was 16.6 months. Twenty-five patients were randomized to a home-exercise cohort, and 26 patients were randomized to a formal-outpatient-PT cohort. There were no significant differences in demographics between cohorts. At 6 weeks, the home-exercise cohort had better function as indicated by a significantly lower mean DASH score compared with the PT cohort (p = 0.021). At 3 months, 6 months, and final follow-up, there were no significant differences between cohorts for any outcome measure. Patients who performed home exercises after sustaining a nondisplaced or minimally displaced fracture of the radial head or neck demonstrated better early function at 6 weeks compared with patients who received formal PT. After 6 weeks, there were no significant differences in outcomes. These data suggest that prescribing PT for patients who have an isolated nondisplaced or minimally displaced fracture of the radial head or neck is not cost-effective and that instructing the patient to perform self-directed exercises will be followed by a similar outcome. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The Effect of Very High versus Very Low Sustained Loading on the Lower Back and Knees in Middle Life

PubMed Central

Milgrom, Yael; Constantini, Naama; Applbaum, Yaakov; Radeva-Petrova, Denitsa; Finestone, Aharon S.

2013-01-01

To evaluate the effect of the extremes of long term high and low physical activities on musculoskeletal heath in middle age, a historical cohort study was performed. The MRI knee and back findings of 25 randomly selected subjects who were inducted into the armed forces in 1983 and served at least 3 years as elite infantry soldiers were compared 25 years later, with 20 randomly selected subjects who were deferred from army service for full time religious studies at the same time. Both cohorts were from the same common genome. The two primary outcome measures were degenerative lumbar disc disease evaluated by the Pfirrmann score and degenerative knee changes evaluated by the WORMS score. At the 25-year follow up, the mean Pfirrmann score (8.6) for the L1 to S1 level of the elite infantry group was significantly higher than that of the sedentary group (6.7), (P = 0.003). There was no statistically significant difference between the WORMS knee scores between the two cohorts (P = 0.7). In spite of the much greater musculoskeletal loading history of the elite infantry cohort, only their lumbar spines but not their knees showed increased degenerative changes at middle age by MRI criteria. PMID:24093109

Effectiveness of Supplemental Kindergarten Vocabulary Instruction for English Learners: A Randomized Study of Immediate and Longer-Term Effects of Two Approaches

ERIC Educational Resources Information Center

Vadasy, Patricia F.; Sanders, Elizabeth A.; Nelson, J. Ron

2015-01-01

A two-cohort cluster randomized trial was conducted to estimate effects of small-group supplemental vocabulary instruction for at-risk kindergarten English learners (ELs). "Connections" students received explicit instruction in high-frequency decodable root words, and interactive book reading (IBR) students were taught the same words in…

The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1.

PubMed

Jacobson, Jeffrey M; Bosinger, Steven E; Kang, Minhee; Belaunzaran-Zamudio, Pablo; Matining, Roy M; Wilson, Cara C; Flexner, Charles; Clagett, Brian; Plants, Jill; Read, Sarah; Purdue, Lynette; Myers, Laurie; Boone, Linda; Tebas, Pablo; Kumar, Princy; Clifford, David; Douek, Daniel; Silvestri, Guido; Landay, Alan L; Lederman, Michael M

2016-07-01

Immune activation associated with HIV-1 infection contributes to morbidity and mortality. We studied whether chloroquine, through Toll-like receptor (TLR) antagonist properties, could reduce immune activation thought to be driven by TLR ligands, such as gut-derived bacterial elements and HIV-1 RNAs. AIDS Clinical Trials Group A5258 was a randomized, double-blind, placebo-controlled study in 33 HIV-1-infected participants off antiretroviral therapy (ART) and 37 participants on ART. Study participants in each cohort were randomized 1:1 to receive chloroquine 250 mg orally for the first 12 weeks then cross over to placebo for 12 weeks or placebo first and then chloroquine. Combining the periods of chloroquine use in both arms of the on-ART cohort yielded a modest reduction in the proportions of CD8 T cells co-expressing CD38 and DR (median decrease = 3.0%, p = .003). The effect on immune activation in the off-ART cohort was likely confounded by increased plasma HIV-1 RNA during chloroquine administration (median 0.29 log10 increase, p < .001). Transcriptional analyses in the off-ART cohort showed decreased expression of interferon-stimulated genes in 5 of 10 chloroquine-treated participants and modest decreases in CD38 and CCR5 RNAs in all chloroquine-treated participants. Chloroquine modestly reduced immune activation in ART-treated HIV-infected participants. Clinical Trials Registry Number: NCT00819390.

Policy-into-practice for rheumatoid arthritis: randomized controlled trial and cohort study of e-learning targeting improved physiotherapy management.

PubMed

Fary, Robyn E; Slater, Helen; Chua, Jason; Ranelli, Sonia; Chan, Madelynn; Briggs, Andrew M

2015-07-01

To examine the effectiveness of a physiotherapy-specific, web-based e-learning platform, "RAP-el," in best-practice management of rheumatoid arthritis (RA) using a single-blind, randomized controlled trial (RCT) and prospective cohort study. Australian-registered physiotherapists were electronically randomized into intervention and control groups. The intervention group accessed RAP-eL over 4 weeks. Change in self-reported confidence in knowledge and skills was compared between groups at the end of the RCT using linear regression conditioned for baseline scores by a blinded assessor, using intent-to-treat analysis. Secondary outcomes included physiotherapists' satisfaction with RA management and responses to RA-relevant clinical statements and practice-relevant vignettes. Retention was evaluated in a cohort study 8 weeks after the RCT. Eighty physiotherapists were randomized into the intervention and 79 into the control groups. Fifty-six and 48, respectively, provided baseline data. Significant between-group differences were observed for change in confidence in knowledge (mean difference 8.51; 95% confidence interval [95% CI] 6.29, 10.73; effect size 1.62) and skills (mean difference 7.26; 95% CI 5.1, 9.4; effect size 1.54), with the intervention group performing better. Satisfaction in ability to manage RA, 4 of the 6 clinical statements, and responses to vignettes demonstrated significant improvement in the intervention group. Although 8-week scores showed declines in most outcomes, their clinical significance remains uncertain. RAP-eL can improve self-reported confidence, likely practice behaviors and satisfaction in physiotherapists' ability to manage people with RA, and improve their clinical knowledge in several areas of best-practice RA management in the short term. © 2015, American College of Rheumatology.

Risk of stroke in patients with patent foramen ovale: an updated meta-analysis of observational studies.

PubMed

Ma, Bing; Liu, Guangcong; Chen, Xin; Zhang, Jianming; Liu, Yiting; Shi, Jingpu

2014-01-01

Although patent foramen ovale (PFO) is considered to be associated with cryptogenic stroke (CS), there remains an ongoing disputation on this issue because of unstable results from randomized controlled trials. The aim of this study was to reassess the PFO effect on stroke through observational data. An electronic search of PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were finished. Only case-control studies and cohort studies in Chinese or English were included in the analysis. Then random-effected meta-analysis models were performed to assess the association between PFO and stroke. Twelve case-control studies and 6 cohort studies were eligible. Case-control studies showed strong association between PFO and CS (odds ratio [OR]: 2.94, 95% confidence interval [CI]: 2.06, 4.20; P < .001), but cohort studies failed to demonstrate a significant association (hazard ratio [HR]: 1.28, 95% CI: .91, 1.80; P = .155). Subgroup analysis revealed that the pooled OR decreased significantly when the region was limited to the United States (OR: 1.52, 95% CI: 1.00, 2.32; P = .083). OR of studies that adjusted major confounders was 1.74 (95% CI: 1.22, 2.47; P = .119) and high-quality studies was 1.68 (95% CI: 1.14, 2.47; P = .072). For cohort studies, a weak statistical association was observed in using transesophageal echocardiography (TEE) studies (HR: 1.45, 95% CI: 1.06, 2.01; P = .138) and follow-up years less than 4 years' studies (HR: 1.45, 95% CI: 1.00, 2.09; P = .064). Although case-control studies still show a positive effect of PFO on stroke, the results of cohort challenged the credibility. Further trial data are needed to confirm the effect of PFO on stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Pelvic floor muscle training for bowel dysfunction following colorectal cancer surgery: A systematic review.

PubMed

Lin, Kuan-Yin; Granger, Catherine L; Denehy, Linda; Frawley, Helena C

2015-11-01

To identify, evaluate and synthesize the evidence examining the effectiveness of pelvic floor muscle training (PFMT) on bowel dysfunction in patients who have undergone colorectal cancer surgery. Eight electronic databases (MEDLINE 1950-2014; CINAHL 1982-2014; EMBASE 1980-2014; Scopus 1823-2014; PsycINFO 1806-2014; Web of Science 1970-2014; Cochrane Library 2014; PEDro 1999-2014) were systematically searched in March 2014. Reference lists of identified articles were cross referenced and hand searched. Randomized controlled trials, cohort studies and case series were included if they investigated the effects of conservative treatments, including PFMT on bowel function in patients with colorectal cancer following surgery. Two reviewers independently assessed the risk of bias of studies using the Newcastle-Ottawa Scale (NOS). Six prospective non-randomized studies and two retrospective studies were included. The mean (SD) NOS risk of bias score was 4.9 (1.2) out of 9; studies were limited by a lack of non-exposed cohort, lack of independent blinded assessment, heterogeneous treatment protocols, and lack of long-term follow-up. The majority of studies reported significant improvements in stool frequency, incontinence episodes, severity of fecal incontinence, and health-related quality of life (HRQoL) after PFMT. Meta-analysis was not possible due to lack of randomized controlled trials. Pelvic floor muscle training for patients following surgery for colorectal cancer appears to be associated with improvements in bowel function and HRQoL. Results from non-randomized studies are promising but randomized controlled trials with sufficient power are needed to confirm the effectiveness of PFMT in this population. © 2014 Wiley Periodicals, Inc.

Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial.

PubMed

Nunn, Andrew J; Rusen, I D; Van Deun, Armand; Torrea, Gabriela; Phillips, Patrick P J; Chiang, Chen-Yuan; Squire, S Bertel; Madan, Jason; Meredith, Sarah K

2014-09-09

In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients with HIV-coinfection. STREAM is a multi-centre randomized trial of non-inferiority design comparing a nine-month regimen to the treatment currently recommended by the World Health Organization in patients with MDR pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health economics data are being collected on all patients in selected sites. The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but for this regimen to be recommended more widely than in a research setting, robust evidence is needed from a randomized clinical trial. Results from the STREAM trial together with data from ongoing cohorts should provide the evidence necessary to revise current recommendations for the treatment for MDR-TB. This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.

Preoperative intra-aortic balloon pump in patients undergoing coronary bypass surgery: a systematic review and meta-analysis.

PubMed

Dyub, Adel M; Whitlock, Richard P; Abouzahr, Labib L; Cinà, Claudio S

2008-01-01

To assess the effectiveness of preoperative intra-aortic balloon pump (IABP) placement in high-risk patients undergoing coronary bypass surgery (CABG). The primary outcome was hospital mortality and secondary outcomes were IABP-related complications (bleeding, leg ischemia, aortic dissection). MEDLINE, EMBASE, Cochrane registry of Controlled Trials, and reference lists of relevant articles were searched. We included randomized controlled trials (RCTs), and cohort studies that fulfilled our a priori inclusion criteria. Eligibility decisions, relevance, study validity, and data extraction were performed in duplicate using pre-specified criteria. Meta-analysis was conducted using a random effects model. Ten publications fulfilled our eligibility criteria, of which four were RCTs and six were cohort studies with controls. There were statistical as well as clinical heterogeneity among included studies. A total of 1034 patients received preoperative IABP and 1329 did not receive preoperative IABP. The pooled odds ratio (OR) for hospital mortality in patients treated with preoperative IABP was 0.41 (95% CI, 0.21-0.82, p = 0.01). The number needed to treat was 17. The pooled OR for hospital mortality from randomized trials was 0.18 (95% CI, 0.06-0.57, p = 0.003) and from cohort studies was 0.54 (95% CI, 0.24-1.2, p = 0.13). Overall, 3.7% (13 of 349) of patients who received preoperative IABP developed either limb ischemia or haematoma at the IABP insertion site, and most of these complications improved after discontinuation of IABP. Evidence from this meta-analysis support the use of preoperative IABP in high-risk patients to reduce hospital mortality.

A randomized controlled study for the treatment of acne vulgaris using high-intensity 414 nm solid state diode arrays.

PubMed

Ash, Caerwyn; Harrison, Anna; Drew, Samantha; Whittall, Rebecca

2015-01-01

The treatment of acne vulgaris poses a challenge to the dermatologist, and the disease causes emotional anxiety for the patient. The treatment of acne vulgaris may be well-suited to home-use applications, where sufferers may be too embarrassed to seek medical treatment. This randomized controlled study is designed to quantify the effectiveness of using a blue light device in a therapy combined with proprietary creams, in the investigation of a self-treatment regimen. A total of 41 adults with mild-to-moderate facial inflammatory acne were recruited. The subjects were randomly assigned to combination blue light therapy (n = 26) or control (n = 15). Photography was used for qualitative assessment of lesion counts, at weeks 1, 2, 4, 8, and 12. All subjects in the treatment cohort achieved a reduction in their inflammatory lesion counts after 12 weeks. The mean inflammatory lesion counts reduced by 50.02% in the treatment cohort, and increased by 2.45% in the control cohort. The reduction in inflammatory lesions was typically observable at week-3, and maximal between weeks 8 and 12. The treatment is free of pain and side-effects. The blue light device offers a valuable alternative to antibiotics and potentially irritating topical treatments. Blue light phototherapy, using a narrow-band LED light source, appears to be a safe and effective additional therapy for mild to moderate acne.

A new era of prospective real-world safety evaluation primary report of XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System condition-of-approval post-market study).

PubMed

Krucoff, Mitchell W; Rutledge, David R; Gruberg, Luis; Jonnavithula, Lalitha; Katopodis, John N; Lombardi, William; Mao, Vivian W; Sharma, Samin K; Simonton, Charles A; Tamboli, Hoshedar P; Wang, Jin; Wilburn, Olivia; Zhao, Weiying; Sudhir, Krishnankutty; Hermiller, James B

2011-12-01

The XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System Condition-of-Approval Post-Market study) sought to: 1) evaluate the safety of everolimus-eluting coronary stent systems (EECSS) in a contemporary cohort of real-world subjects; and 2) prospectively test the quality of event reporting with analysis of matched patients from the randomized SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions) trial. Randomized trials have demonstrated the safety and efficacy of EECSS in selected "standard-risk" patients. The XIENCE V USA trial was a prospective, multicenter, single-arm study in unselected patients. The primary endpoint was Academic Research Consortium (ARC)-defined definite and probable stent thrombosis (ST); the co-primary endpoint was the composite of cardiac death and myocardial infarction at 1 year. Secondary analyses included: 1) stratification by standard-risk and extended-risk cohorts; and 2) late ST after dual antiplatelet therapy interruption. Of 5,054 participants (1,875 standard-risk; 3,179 extended-risk), 4,958 (98.1%) reached 1-year follow-up. The rate of ARC-defined definite and probable ST was 0.84% (95% confidence interval [CI]: 0.60% to 1.14%) in the overall population and 0.33% (95% CI: 0.12% to 10.72%) and 1.14% (95% CI: 0.80% to 11.58%) in the standard-risk and extended-risk cohorts, respectively. No late ST was observed after dual antiplatelet therapy interruption in either cohort after 6 months. The composite rate of cardiac death and ARC-defined myocardial infarction was 6.5% (95% CI: 5.79% to 17.17%) in the overall population, 3.8% (95% CI: 2.98% to 14.78%) in the standard-risk cohort, and 8.0% (95% CI: 7.09% to 19.02%) in the extended-risk cohort. This study comprehensively reports ST rates for EECSS in a contemporary real-world population. The absence of ST after dual antiplatelet therapy interruption beyond 6 months in standard-risk and high-risk patients is notable. Consistent safety outcomes between matched standard-risk cohorts from the XIENCE V USA study and the SPIRIT IV randomized trial suggest that this study affords a reliable benchmark for understanding the safety of EECSS in the context of real-world clinical practice. (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval Study; NCT00676520). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1-state) - A prospective multicenter randomized controlled clinical trial using a comprehensive cohort design

PubMed Central

2009-01-01

Background Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation. Methods/Design The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome. Conclusion The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study. Trial registration ClinicalTrials.gov: NCT00964977 PMID:20028566

Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial.

PubMed

Coric, Vladimir; Salloway, Stephen; van Dyck, Christopher H; Dubois, Bruno; Andreasen, Niels; Brody, Mark; Curtis, Craig; Soininen, Hilkka; Thein, Stephen; Shiovitz, Thomas; Pilcher, Gary; Ferris, Steven; Colby, Susan; Kerselaers, Wendy; Dockens, Randy; Soares, Holly; Kaplita, Stephen; Luo, Feng; Pachai, Chahin; Bracoud, Luc; Mintun, Mark; Grill, Joshua D; Marek, Ken; Seibyl, John; Cedarbaum, Jesse M; Albright, Charles; Feldman, Howard H; Berman, Robert M

2015-11-01

Early identification of Alzheimer disease (AD) is important for clinical management and affords the opportunity to assess potential disease-modifying agents in clinical trials. To our knowledge, this is the first report of a randomized trial to prospectively enrich a study population with prodromal AD (PDAD) defined by cerebrospinal fluid (CSF) biomarker criteria and mild cognitive impairment (MCI) symptoms. To assess the safety of the γ-secretase inhibitor avagacestat in PDAD and to determine whether CSF biomarkers can identify this patient population prior to clinical diagnosis of dementia. A randomized, placebo-controlled phase 2 clinical trial with a parallel, untreated, nonrandomized observational cohort of CSF biomarker-negative participants was conducted May 26, 2009, to July 9, 2013, in a multicenter global population. Of 1358 outpatients screened, 263 met MCI and CSF biomarker criteria for randomization into the treatment phase. One hundred two observational cohort participants who met MCI criteria but were CSF biomarker-negative were observed during the same study period to evaluate biomarker assay sensitivity. Oral avagacestat or placebo daily. Safety and tolerability of avagacestat. Of the 263 participants in the treatment phase, 132 were randomized to avagacestat and 131 to placebo; an additional 102 participants were observed in an untreated observational cohort. Avagacestat was relatively well tolerated with low discontinuation rates (19.6%) at a dose of 50 mg/d, whereas the dose of 125 mg/d had higher discontinuation rates (43%), primarily attributable to gastrointestinal tract adverse events. Increases in nonmelanoma skin cancer and nonprogressive, reversible renal tubule effects were observed with avagacestat. Serious adverse event rates were higher with avagacestat (49 participants [37.1%]) vs placebo (31 [23.7%]), attributable to the higher incidence of nonmelanoma skin cancer. At 2 years, progression to dementia was more frequent in the PDAD cohort (30.7%) vs the observational cohort (6.5%). Brain atrophy rate in PDAD participants was approximately double that of the observational cohort. Concordance between abnormal amyloid burden on positron emission tomography and pathologic CSF was approximately 87% (κ = 0.68; 95% CI, 0.48-0.87). No significant treatment differences were observed in the avagacestat vs placebo arm in key clinical outcome measures. Avagacestat did not demonstrate efficacy and was associated with adverse dose-limiting effects. This PDAD population receiving avagacestat or placebo had higher rates of clinical progression to dementia and greater brain atrophy compared with CSF biomarker-negative participants. The CSF biomarkers and amyloid positron emission tomography imaging were correlated, suggesting that either modality could be used to confirm the presence of cerebral amyloidopathy and identify PDAD. clinicaltrials.gov Identifier: NCT00890890.

GFR at Initiation of Dialysis and Mortality in CKD: A Meta-analysis

PubMed Central

Susantitaphong, Paweena; Altamimi, Sarah; Ashkar, Motaz; Balk, Ethan M.; Stel, Vianda S.; Wright, Seth; Jaber, Bertrand L.

2012-01-01

Background The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis at higher glomerular filtration rate (GFR) has increased over the past decade. Recent data suggest that higher GFR may be associated with increased mortality. Study Design A meta-analysis of cohort studies and trials. Setting & Population Patients with advanced CKD. Selection Criteria for Studies We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis initiation and mortality. Predictor estimated or calculated GFR at dialysis initiation. Outcome Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality. Results Sixteen cohort studies and one randomized controlled trial were identified (n=1,081,116). By meta-analysis, restricted to the 15 cohorts (n=1,079,917), higher GFR at dialysis initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03–1.05; P<0.001). However, there was significant heterogeneity (I2=97%; P<0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR 1.03; 95% CI 1.02, 1.04; P<0.001; residual I2=97%). The highest mortality risk was observed in hemodialysis cohorts (HR 1.05; 95% CI 1.02, 1.08; P<0.001) whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR 1.04; 95% CI 0.99, 1.08, P=0.11; residual I2=98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR 0.80; 95% CI 0.71, 0.91; P=0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR 1.04; 95% CI 1.03, 1.05; P<0.001; residual I2=97%). Limitations Paucity of randomized controlled trials; different methods for determining GFR; and substantial heterogeneity. Conclusions Higher estimated rather than calculated GFR at dialysis initiation is associated with a higher mortality risk among patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study. PMID:22465328

Developing and validating a novel metabolic tumor volume risk stratification system for supplementing non-small cell lung cancer staging.

PubMed

Pu, Yonglin; Zhang, James X; Liu, Haiyan; Appelbaum, Daniel; Meng, Jianfeng; Penney, Bill C

2018-06-07

We hypothesized that whole-body metabolic tumor volume (MTVwb) could be used to supplement non-small cell lung cancer (NSCLC) staging due to its independent prognostic value. The goal of this study was to develop and validate a novel MTVwb risk stratification system to supplement NSCLC staging. We performed an IRB-approved retrospective review of 935 patients with NSCLC and FDG-avid tumor divided into modeling and validation cohorts based on the type of PET/CT scanner used for imaging. In addition, sensitivity analysis was conducted by dividing the patient population into two randomized cohorts. Cox regression and Kaplan-Meier survival analyses were performed to determine the prognostic value of the MTVwb risk stratification system. The cut-off values (10.0, 53.4 and 155.0 mL) between the MTVwb quartiles of the modeling cohort were applied to both the modeling and validation cohorts to determine each patient's MTVwb risk stratum. The survival analyses showed that a lower MTVwb risk stratum was associated with better overall survival (all p < 0.01), independent of TNM stage together with other clinical prognostic factors, and the discriminatory power of the MTVwb risk stratification system, as measured by Gönen and Heller's concordance index, was not significantly different from that of TNM stage in both cohorts. Also, the prognostic value of the MTVwb risk stratum was robust in the two randomized cohorts. The discordance rate between the MTVwb risk stratum and TNM stage or substage was 45.1% in the modeling cohort and 50.3% in the validation cohort. This study developed and validated a novel MTVwb risk stratification system, which has prognostic value independent of the TNM stage and other clinical prognostic factors in NSCLC, suggesting that it could be used for further NSCLC pretreatment assessment and for refining treatment decisions in individual patients.

A prospective randomized cohort study evaluating 3 weeks vs 6 weeks of oral antibiotic treatment in the setting of "maximal medical therapy" for chronic rhinosinusitis.

PubMed

Sreenath, Satyan B; Taylor, Robert J; Miller, Justin D; Ambrose, Emily C; Rawal, Rounak B; Ebert, Charles S; Senior, Brent A; Zanation, Adam M

2015-09-01

Surprisingly, little literature exists evaluating the optimal duration of antibiotic treatment in "maximal medical therapy" for chronic rhinosinusitis (CRS). As such, we investigated whether 3 weeks vs 6 weeks of antibiotic therapy resulted in significant differences in clinical response. A prospective, randomized cohort study was performed with patients assigned to 3-week or 6-week cohorts. Our primary outcome was failure of "maximal medical therapy" and surgical recommendation. Secondary outcomes included changes in pretherapy and posttherapy scores for the Rhinosinusitis Disability Index (RSDI), Chronic Sinusitis Survey (CSS), and computed tomography (CT)-based Lund-Mackay (LM) evaluation. Analyses were substratified based on presence of nasal polyps. Forty patients were randomized to the 3-week or 6-week treatment cohorts, with near-complete clinical follow-up achieved. No significant difference was found between the proportion of patients who failed medical therapy and were deemed surgical candidates between the 2 cohorts (71% vs 68%, p = 1.000). No significant difference was found in the change of RSDI or CSS scores in the 3 vs 6 weeks of treatment groups (mean ± standard error of the mean [SEM]; RSDI: 9.62 ± 4.14 vs 1.53 ± 4.01, p = 0.868; CSS: 5.75 ± 4.36 vs 9.65 ± 5.34, p = 0.573). Last, no significant difference was found in the change of LM scores (3.35 ± 1.11 vs 1.53 ± 0.81, p = 0.829). Based on this data, there is little difference in clinical outcomes between 3 weeks vs 6 weeks of antibiotic treatment as part of "maximal medical therapy" for CRS. Increased duration of antibiotic treatment theoretically may increase risk from side effects and creates higher healthcare costs. © 2015 ARS-AAOA, LLC.

A hybrid Bayesian hierarchical model combining cohort and case-control studies for meta-analysis of diagnostic tests: Accounting for partial verification bias.

PubMed

Ma, Xiaoye; Chen, Yong; Cole, Stephen R; Chu, Haitao

2016-12-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities, and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. © The Author(s) 2014.

A Hybrid Bayesian Hierarchical Model Combining Cohort and Case-control Studies for Meta-analysis of Diagnostic Tests: Accounting for Partial Verification Bias

PubMed Central

Ma, Xiaoye; Chen, Yong; Cole, Stephen R.; Chu, Haitao

2014-01-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. PMID:24862512

Chronic urinary tract infection and bladder carcinoma risk: a meta-analysis of case-control and cohort studies.

PubMed

Akhtar, Saeed; Al-Shammari, Ahmad; Al-Abkal, Jarrah

2018-02-05

This meta-analysis of published case-control and cohort studies sought to quantify the magnitude and direction of association between chronic UTI (defined as the infection of the urinary tract that either does not respond to treatment or keeps recurring) and risk of bladder carcinoma (BCa) (i.e., including mainly urothelial carcinoma, squamous cell carcinoma or adenocarcinoma). A literature search was conducted using Medline, Embase, Ovid, Web of Science, Science Direct and Cochrane Library, which was supplemented with manual search of reference lists of the identified articles. Case-control and cohort studies examining UTI as a predictor of BCa risk published through June 2016 were eligible. Using random-effects models, odds ratios (OR) or relative risks (RR) from eligible studies were combined to synthesize summary effect estimates. The included studies were assessed for methodological quality and potential publication bias. Heterogeneity by study characteristics was examined by sub-group and meta-regression analyses. Eighteen case-control and three cohort studies published between 1963 and 2016 were eligible. Random-effects models showed that UTI was significantly associated with an increased BCa risk both in case-control studies (summary OR RE  = 2.33; 95% CI 1.86, 2.92) and cohort studies (summary RR RE  = 2.88; 95% CI 1.20, 6.89). The observed relationship of UTI with an increased BCa risk was independent of the study characteristics considered. No significant publication bias was detected. Chronic UTI was significantly and independently associated with an increased BCa risk. However, due to the presence of high between-study heterogeneity and inconsistent patterns of adjusted confounding effects, more data are needed to clarify the role of chronic UTI in causation of BCa and if established, prompt and effective treatment of UTI may minimize a substantial proportion of BCa risk.

Dynamic models for estimating the effect of HAART on CD4 in observational studies: Application to the Aquitaine Cohort and the Swiss HIV Cohort Study.

PubMed

Prague, Mélanie; Commenges, Daniel; Gran, Jon Michael; Ledergerber, Bruno; Young, Jim; Furrer, Hansjakob; Thiébaut, Rodolphe

2017-03-01

Highly active antiretroviral therapy (HAART) has proved efficient in increasing CD4 counts in many randomized clinical trials. Because randomized trials have some limitations (e.g., short duration, highly selected subjects), it is interesting to assess the effect of treatments using observational studies. This is challenging because treatment is started preferentially in subjects with severe conditions. This general problem had been treated using Marginal Structural Models (MSM) relying on the counterfactual formulation. Another approach to causality is based on dynamical models. We present three discrete-time dynamic models based on linear increments models (LIM): the first one based on one difference equation for CD4 counts, the second with an equilibrium point, and the third based on a system of two difference equations, which allows jointly modeling CD4 counts and viral load. We also consider continuous-time models based on ordinary differential equations with non-linear mixed effects (ODE-NLME). These mechanistic models allow incorporating biological knowledge when available, which leads to increased statistical evidence for detecting treatment effect. Because inference in ODE-NLME is numerically challenging and requires specific methods and softwares, LIM are a valuable intermediary option in terms of consistency, precision, and complexity. We compare the different approaches in simulation and in illustration on the ANRS CO3 Aquitaine Cohort and the Swiss HIV Cohort Study. © 2016, The International Biometric Society.

Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.

PubMed

Tenforde, Mark W; Yadav, Ashish; Dowdy, David W; Gupte, Nikhil; Shivakoti, Rupak; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Santos, Breno; Poongulali, Selvamuthu; Tripathy, Srikanth; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Christian, Parul; Semba, Richard D; Campbell, Thomas B; Gupta, Amita

2017-07-01

Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral therapy (ART) initiation in HIV-infected individuals is not well characterized. We conducted a case-cohort study (n = 332) within a randomized trial comparing 3 ART regimens in 1571 HIV treatment-naive adults from 9 countries. A subcohort of 30 patients was randomly selected from each country (n = 270). Cases (n = 77; main cohort = 62, random subcohort = 15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pretreatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pretreatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models. Median pretreatment CD4 T-cell count was 170 cells/mm; 47.3% were women; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, previous TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pretreatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI: 1.54 to 18.43) and vitamin D (aHR 3.66, 95% CI: 1.16 to 11.51) were associated with TB post-ART. In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV-infected patients starting ART in resource-limited highly-TB-endemic settings.

Mixed models, linear dependency, and identification in age-period-cohort models.

PubMed

O'Brien, Robert M

2017-07-20

This paper examines the identification problem in age-period-cohort models that use either linear or categorically coded ages, periods, and cohorts or combinations of these parameterizations. These models are not identified using the traditional fixed effect regression model approach because of a linear dependency between the ages, periods, and cohorts. However, these models can be identified if the researcher introduces a single just identifying constraint on the model coefficients. The problem with such constraints is that the results can differ substantially depending on the constraint chosen. Somewhat surprisingly, age-period-cohort models that specify one or more of ages and/or periods and/or cohorts as random effects are identified. This is the case without introducing an additional constraint. I label this identification as statistical model identification and show how statistical model identification comes about in mixed models and why which effects are treated as fixed and which are treated as random can substantially change the estimates of the age, period, and cohort effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial.

PubMed

Rao, Sunil V; Hess, Connie N; Barham, Britt; Aberle, Laura H; Anstrom, Kevin J; Patel, Tejan B; Jorgensen, Jesse P; Mazzaferri, Ernest L; Jolly, Sanjit S; Jacobs, Alice; Newby, L Kristin; Gibson, C Michael; Kong, David F; Mehran, Roxana; Waksman, Ron; Gilchrist, Ian C; McCourt, Brian J; Messenger, John C; Peterson, Eric D; Harrington, Robert A; Krucoff, Mitchell W

2014-08-01

This study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial. Women are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear. Women undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population. The trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access. In this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Physical Examination-Indicated Cerclage: A Systematic Review and Meta-analysis.

PubMed

Ehsanipoor, Robert M; Seligman, Neil S; Saccone, Gabriele; Szymanski, Linda M; Wissinger, Christina; Werner, Erika F; Berghella, Vincenzo

2015-07-01

To estimate the effectiveness of physical examination-indicated cerclage in the setting of second-trimester cervical dilatation by systematic review and meta-analysis of published studies. We searched MEDLINE, EMBASE, Scopus, ClinicalTrials.gov, Web of Science, and the Cochrane Library for studies published between 1966 and 2014 that evaluated cervical cerclage for the treatment of cervical insufficiency. The search yielded 6,314 citations. We included cohort studies and randomized controlled trials comparing cerclage placement with expectant management of women with cervical dilatation between 14 and 27 weeks of gestation. Two investigators independently reviewed each citation for inclusion or exclusion and discordant decisions were arbitrated by a third reviewer. Summary estimates were reported as the mean difference and 95% confidence interval (CI) for continuous variables or relative risk and with 95% CI for dichotomous outcomes. Fixed- and random-effects meta-analysis was used, depending on heterogeneity. Ten studies met inclusion criteria and were included in the final analysis. One was a randomized controlled trial, two were prospective cohort studies, and the remaining seven were retrospective cohort studies. Of the 757 women, 485 (64%) underwent physical examination-indicated cerclage placement and 272 (36%) were expectantly managed. Cerclage was associated with increased neonatal survival (71% compared with 43%; relative risk 1.65, 95% CI 1.19-2.28) and prolongation of pregnancy (mean difference 33.98 days, 95% CI 17.88-50.08). Physical examination-indicated cerclage is associated with a significant increase in neonatal survival and prolongation of pregnancy of approximately 1 month when compared with no such cerclage. The strength of this conclusion is limited by the potential for bias in the included studies.

Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the recombinant factor VIIa variant BAY 86-6150 in hemophilia.

PubMed

Mahlangu, J N; Coetzee, M J; Laffan, M; Windyga, J; Yee, T T; Schroeder, J; Haaning, J; Siegel, J E; Lemm, G

2012-05-01

BAY 86-6150 is a new human recombinant factor VIIa variant developed for high procoagulant activity and longer action in people with hemophilia with inhibitors. To investigate the safety, tolerability, pharmacodynamics, pharmacokinetics and immunogenicity of BAY 86-6150 in non-bleeding hemophilia subjects. The study included non-bleeding men (18-65 years of age) with moderate or severe hemophilia A or B with or without inhibitors. Sixteen subjects were randomized 3 : 1 to four cohorts of escalating doses of BAY 86-6150 (6.5, 20, 50 or 90 μg kg(-1) [n = 3 per cohort]) or placebo (n = 1 per cohort); an independent data-monitoring committee reviewed previous cohort data before the next dose escalation. Blood sampling was performed predose and postdose; subjects were monitored for 50 days postdose. At the tested doses, BAY 86-6150 was not associated with clinically significant adverse events or dose-limiting toxicities. BAY 86-6150 pharmacokinetics exhibited a linear dose response, with a half-life of 5-7 h. Subjects demonstrated consistent, dose-dependent thrombin generation ex vivo in platelet-poor plasma (PPP) (mean peak effect, 26-237 nm thrombin from 6.5 to 90 μg kg(-1)). Peak thrombin levels over time paralleled BAY 86-6150, with thrombin kinetics appearing to be slightly shorter; thus, circulating BAY 86-6150 retained activity. There were corresponding decreases in activated partial thromboplastin and prothrombin times. No subject developed de novo anti-BAY 86-6150 neutralizing antibodies during the 50-day follow-up. In this first-in-human, multicenter, randomized, double-blind, placebo-controlled, single-dose escalation study, BAY 86-6150 was tolerated at the highest dose (90 μg kg(-1)), with no safety concerns. Safety and efficacy will be further evaluated in phase II/III studies. © 2012 International Society on Thrombosis and Haemostasis.

A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.

PubMed

Alexander, Dominik D; Miller, Paige E; Van Elswyk, Mary E; Kuratko, Connye N; Bylsma, Lauren C

2017-01-01

To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Stressful life events and cancer risk

PubMed Central

Bergelt, C; Prescott, E; Grønbæk, M; Koch, U; Johansen, C

2006-01-01

In a prospective cohort study in Denmark of 8736 randomly selected people, no evidence was found among 1011 subjects who developed cancer that self-reported stressful major life events had increased their risk for cancer. PMID:17106440

The generalizability of bronchiectasis randomized controlled trials: A multicentre cohort study.

PubMed

Chalmers, James D; McDonnell, Melissa J; Rutherford, Robert; Davidson, John; Finch, Simon; Crichton, Megan; Dupont, Lieven; Hill, Adam T; Fardon, Thomas C; De Soyza, Anthony; Aliberti, Stefano; Goeminne, Pieter

2016-03-01

Randomized controlled trials (RCTs) for bronchiectasis have experienced difficulties with recruitment and in reaching their efficacy end-points. To estimate the generalizability of such studies we applied the eligibility criteria for major RCTs in bronchiectasis to 6 representative observational European Bronchiectasis cohorts. Inclusion and exclusion criteria from 10 major RCTs were applied in each cohort. Demographics and outcomes were compared between patients eligible and ineligible for RCTs. 1672 patients were included. On average 33.0% were eligible for macrolide trials, 15.0% were eligible for inhaled antibiotic trials, 15.9% for the DNAse study and 47.7% were eligible for a study of dry powder mannitol. Within these groups, some trials were highly selective with only 1-9% of patients eligible. Eligible patients were generally more severe with higher mortality during follow-up (mean 17.2 vs 9.0% for macrolide studies, 19.2%% vs 10.7% for inhaled antibiotic studies), and a higher frequency of exacerbations than ineligible patients. As up to 93% of patients were ineligible for studies, however, numerically more deaths and exacerbations occurred in ineligible patient across studies (mean 56% of deaths occurred in ineligible patients across all studies). Our data suggest that patients enrolled in RCT's in bronchiectasis are only partially representative of patients in clinical practice. The majority of mortality and morbidity in bronchiectasis occurs in patients ineligible for many current trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systematic review and meta-analysis of secondary prophylaxis for prevention of HIV-related toxoplasmic encephalitis relapse using trimethoprim-sulfamethoxazole.

PubMed

Connolly, Mark P; Haitsma, Gertruud; Hernández, Adrián V; Vidal, José E

2017-09-01

A recent systematic literature and meta-analysis reported relative efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during secondary prophylaxis with TMP-SMX, and further explored differences in relapse rates prior to introduction of highly active antiretroviral therapy (HAART) and the widespread adoption of HAART. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663 were excluded after abstract screening, and 38 were excluded after full review leaving 6 studies for extraction. We performed double data extraction with a third-party adjudicator. Study designs varied with only one randomized study, four prospective cohorts and one retrospective cohort. Relapse rates were transformed using the Freeman-Tukey method and pooled using both fixed-effect and random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI = 6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates between pre- and post-HAART studies were contrary to what might be expected based on known benefits of HAART therapy in this population. Nevertheless, cautious interpretation is necessary considering the heterogeneity of the included studies and a limited number of subjects receiving TMP-SMX reported in the post-HAART era.

CORTISOL CORRELATES WITH SEVERITY OF ILLNESS AND POORLY REFLECTS ADRENAL FUNCTION IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME

PubMed Central

Yehya, Nadir; Vogiatzi, Maria G.; Thomas, Neal J.; Srinivasan, Vijay

2016-01-01

Objective To test the association between random cortisol and severity of illness in a “real-world” application of current guidelines. Study design We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels prior to potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 μg/dL and ≥ 18 μg/dL, and hydrocortisone use and outcomes compared. Results Of 357 children with ARDS, 155 (15 non-survivors, 10%) had vasopressors initiated with cortisol drawn prior to possible hydrocortisone use. Patients with cortisol < 18 μg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum p < 0.05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 μg/dL. In patients with cortisol ≥ 18 μg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. Conclusions In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 μg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function. PMID:27283464

Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial.

PubMed

Pianko, Stephen; Flamm, Steven L; Shiffman, Mitchell L; Kumar, Sonal; Strasser, Simone I; Dore, Gregory J; McNally, John; Brainard, Diana M; Han, Lingling; Doehle, Brian; Mogalian, Erik; McHutchison, John G; Rabinovitz, Mordechai; Towner, William J; Gane, Edward J; Stedman, Catherine A M; Reddy, K Rajender; Roberts, Stuart K

2015-12-01

Effective treatment options are needed for patients with genotype 1 or 3 hepatitis C virus (HCV) infection in whom previous therapy has failed. To assess the efficacy and safety of sofosbuvir plus velpatasvir, with and without ribavirin, in treatment-experienced patients. Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01909804). 58 sites in Australia, New Zealand, and the United States. Treatment-experienced adults with genotype 3 HCV infection without cirrhosis (cohort 1) and with compensated cirrhosis (cohort 2) and patients with genotype 1 HCV infection that was unsuccessfully treated with a protease inhibitor with peginterferon and ribavirin (50% could have compensated cirrhosis) (cohort 3). All patients received 12 weeks of treatment that included 400 mg of sofosbuvir once daily. Patients in each cohort were randomly assigned to 25 mg of velpatasvir once daily with or without ribavirin or 100 mg of velpatasvir once daily with or without ribavirin. Proportion of patients with sustained virologic response at week 12 after treatment (SVR12). In cohort 1, SVR12 rates were 85% with 25 mg of velpatasvir, 96% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 100% with 100 mg of velpatasvir plus ribavirin. In cohort 2, SVR12 rates were 58% with 25 mg of velpatasvir, 84% with 25 mg of velpatasvir plus ribavirin, 88% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. In cohort 3, SVR12 rates were 100% with 25 mg of velpatasvir, 97% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. The most common adverse events were headache, fatigue, and nausea. Treatment assignments were not blinded, and no inferential statistics were planned. Treatment with 400 mg of sofosbuvir plus 100 mg of velpatasvir for 12 weeks was well-tolerated and highly effective in treatment-experienced patients with genotype 1 or 3 HCV infection. Gilead Sciences.

Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies.

PubMed

Azad, Meghan B; Abou-Setta, Ahmed M; Chauhan, Bhupendrasinh F; Rabbani, Rasheda; Lys, Justin; Copstein, Leslie; Mann, Amrinder; Jeyaraman, Maya M; Reid, Ashleigh E; Fiander, Michelle; MacKay, Dylan S; McGavock, Jon; Wicklow, Brandy; Zarychanski, Ryan

2017-07-17

Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points. From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m 2 ; 95% confidence interval [CI] -1.10 to 0.36; I 2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I 2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome. Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749. © 2017 Canadian Medical Association or its licensors.

Marginal Structural Models for Case-Cohort Study Designs to Estimate the Association of Antiretroviral Therapy Initiation With Incident AIDS or Death

PubMed Central

Cole, Stephen R.; Hudgens, Michael G.; Tien, Phyllis C.; Anastos, Kathryn; Kingsley, Lawrence; Chmiel, Joan S.; Jacobson, Lisa P.

2012-01-01

To estimate the association of antiretroviral therapy initiation with incident acquired immunodeficiency syndrome (AIDS) or death while accounting for time-varying confounding in a cost-efficient manner, the authors combined a case-cohort study design with inverse probability-weighted estimation of a marginal structural Cox proportional hazards model. A total of 950 adults who were positive for human immunodeficiency virus type 1 were followed in 2 US cohort studies between 1995 and 2007. In the full cohort, 211 AIDS cases or deaths occurred during 4,456 person-years. In an illustrative 20% random subcohort of 190 participants, 41 AIDS cases or deaths occurred during 861 person-years. Accounting for measured confounders and determinants of dropout by inverse probability weighting, the full cohort hazard ratio was 0.41 (95% confidence interval: 0.26, 0.65) and the case-cohort hazard ratio was 0.47 (95% confidence interval: 0.26, 0.83). Standard multivariable-adjusted hazard ratios were closer to the null, regardless of study design. The precision lost with the case-cohort design was modest given the cost savings. Results from Monte Carlo simulations demonstrated that the proposed approach yields approximately unbiased estimates of the hazard ratio with appropriate confidence interval coverage. Marginal structural model analysis of case-cohort study designs provides a cost-efficient design coupled with an accurate analytic method for research settings in which there is time-varying confounding. PMID:22302074

Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis.

PubMed

Hartwig, Fernando Pires; Horta, Bernardo Lessa; Smith, George Davey; de Mola, Christian Loret; Victora, Cesar Gomes

2016-10-01

Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population. We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis. In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with -0.26 (95% CI: -0.33; -0.19) kg/m 2 in BMI and -0.31 (95% CI: -0.46; -0.16) and -0.35 (95% CI: -0.46; -0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m 2 ] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP. Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus

PubMed Central

Chadha, A; Fettiplace, J; Kleoudis, C; Bass, D; Roth, D; Gordon, D

2017-01-01

Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11–23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little difference was observed between cohorts across a broad response, up to 23 serotypes. Eight (23.5%) patients experienced an adverse event considered by the investigator to be treatment-related in the pre-belimumab cohort and four (8.9%) in the belimumab-concurrent cohort; seven patients experienced non-fatal serious adverse events (pre-belimumab cohort, 11.8% [n = 4]; concurrent-belimumab cohort, 6.7% [n = 3]), and no deaths were reported. Conclusion The proportion of patients generating a response to ≥1 pneumococcal serotype did not differ between the pre-belimumab and belimumab-concurrent cohorts; the proportions were also comparable across a broader response (from ≥2 serotypes to 23 serotypes). PMID:28467293

A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus.

PubMed

Chatham, W; Chadha, A; Fettiplace, J; Kleoudis, C; Bass, D; Roth, D; Gordon, D

2017-12-01

Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11-23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little difference was observed between cohorts across a broad response, up to 23 serotypes. Eight (23.5%) patients experienced an adverse event considered by the investigator to be treatment-related in the pre-belimumab cohort and four (8.9%) in the belimumab-concurrent cohort; seven patients experienced non-fatal serious adverse events (pre-belimumab cohort, 11.8% [ n = 4]; concurrent-belimumab cohort, 6.7% [ n = 3]), and no deaths were reported. Conclusion The proportion of patients generating a response to ≥1 pneumococcal serotype did not differ between the pre-belimumab and belimumab-concurrent cohorts; the proportions were also comparable across a broader response (from ≥2 serotypes to 23 serotypes).

Anthropometric Differences between HIV-Infected Individuals Prior to Antiretroviral Treatment and the General Population from 1998–2007: The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) Cohort and NHANES

PubMed Central

Atkinson, Benjamin E.; Krishnan, Supriya; Cox, Gary; Hulgan, Todd; Collier, Ann C.

2013-01-01

Objective To assess differences in body circumferences and body mass index (BMI, kg/m2) between antiretroviral treatment (ART) naïve HIV-infected and HIV-uninfected persons. Methods Waist, arm, and thigh circumferences and BMI were measured within the ALLRT and NHANES cohorts between 1998 and 2007. ALLRT is a prospective, longitudinal study of U.S. participants enrolled in randomized HIV treatment studies conducted by the AIDS Clinical Trials Group (ACTG). NHANES is a representative group of the US population. The cohorts were analyzed in two time periods, to account for trends towards increased adiposity. Anthropometrics were displayed in percentiles by age and sex. Multiple linear regression models examined differences between cohorts. Results ALLRT had more males (82% versus 48%, p<0.0001), more black participants (32% versus 23%, p<0.0001), and less Hispanics (21% versus 30%, p<0.0001) than NHANES. Mean BMI was smaller in ALLRT males and females compared to NHANES by 1.6–2.4 kg/m2 (p<0.0001). Mean waist and arm circumferences in both sexes and time periods were significantly smaller in ALLRT than in NHANES (p<0.0001). Mean thigh circumference in ALLRT was also smaller than NHANES among males (p<0.0001 in both time periods) and females (p = 0.01 in the early time period). Conclusions Differences in anthropometrics existed prior to ART initiation, in this large national cohort of HIV-infected individuals, compared to a representative HIV-uninfected cohort, indicating that HIV and its complications have important effects on body shape. Further longitudinal examination of anthropometrics in this HIV-infected cohort may provide additional insight into disease risk. Trial Registration NCT00001137 at www.clinicaltrials.gov. PMID:23755215

Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

PubMed

Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

2014-12-12

A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to <18 years of age. Subjects were stratified as follows: Cohort A (≥6 months to <3 years); Cohort B (≥3 years to <9 years); and Cohort C (≥9 years to <18 years). The subject's age and influenza vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Periodontal disease with treatment reduces subsequent cancer risks.

PubMed

Hwang, Ing-Ming; Sun, Li-Min; Lin, Cheng-Li; Lee, Chun-Feng; Kao, Chia-Hung

2014-10-01

The aim of our study was to evaluate the relationship between routine treatment of periodontal disease (PD) and the subsequent risks for cancers in Taiwan. Study participants were selected from the Taiwan National Health Insurance (NHI) system database. The PD with a routine treatment cohort contained 38 902 patients. For each treatment cohort participant, two age- and sex-matched comparison (control) cohort participants were randomly selected. Cox's proportional hazards regression analysis was used to estimate the effects of PD with treatment on the subsequent risk of cancer. The overall risk of developing cancer was significantly lower in the treatment cohort than in the patients without treatment (adjusted Hazard ratio = 0.72, 95% confidence interval = 0.68-0.76). The risks of developing most gastrointestinal tract, lung, gynecological and brain malignancies were significantly lower in the treatment cohort than in the comparison cohort. In contrast, the risks of prostate and thyroid cancers were significantly higher in the treatment cohort than in the comparison cohort. Our findings suggest that PD with treatment is associated with a significantly reduced overall risk of cancer and reduced risks of certain types of cancers. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

PubMed

Handley, Alison; Lloyd, Eric; Roberts, Andrew; Barger, Bruce

2016-01-01

This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5-25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics.

76 FR 66051 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... have no identified disability, (2) youth who do not have an IEP but who have a condition that qualifies... cohorts of youth with an IEP who were studied in the past. Districts and youth will be randomly selected...

Canary TMA — EDRN Public Portal

Cancer.gov

This protocol describes a multi-center, retrospective, case-cohort tissue microarray (TMA) study to evaluate tissue biomarkers for their ability to predict recurrent prostate cancer at the time of radical prostatectomy (RP). Candidate biomarkers will be assessed by performing tissue localization studies on TMAs containing recurrent prostate cancer and non-recurrent prostate cancer. De-identified data will be transferred to a central repository for statistical analysis. Participating institutions will use a variation of case-cohort sampling to randomly select a subset of patients from a retrospectively constructed RP cohort and/or perform selected assays on the cohort. The study endpoint is time to recurrence; of primary interest is five year recurrence free survival. Recurrent prostate cancer is defined by 1) a single serum prostate-specific antigen (PSA) level greater than 0.2 ng/mL after RP and/or 2) receipt of salvage or secondary therapy after RP and/or 3) clinical or radiological evidence of metastatic disease. Non-recurrent prostate cancer is defined as disease with no evidence of recurrence.

Chocolate consumption and risk of atrial fibrillation: Two cohort studies and a meta-analysis.

PubMed

Larsson, Susanna C; Drca, Nikola; Jensen-Urstad, Mats; Wolk, Alicja

2018-01-01

Chocolate consumption has been inconsistently associated with risk of atrial fibrillation (AF). We investigated the association between chocolate consumption and risk of AF in Swedish adults from two cohort studies and conducted a meta-analysis to summarize available evidence from cohort studies on this topic. Our study population comprised 40,009 men from the Cohort of Swedish Men and 32,486 women from the Swedish Mammography Cohort. Incident AF cases were ascertained through linkage with the Swedish National Patient Register. Published cohort studies of chocolate consumption in relation to risk of AF were identified by a PubMed search through September 14, 2017. During a mean follow-up of 14.6 years, AF was diagnosed in 9978 Swedish men and women. Compared with non-consumers, the multivariable hazard ratio of AF for those in the highest category of chocolate consumption (≥3-4 servings/week) was 0.96 (95% CI 0.88-1.04). In a random-effects meta-analysis of 5 cohort studies, including 180,454 participants and 16,356 AF cases, the hazard ratios of AF were 0.97 (95% CI 0.94-1.01) per 2 servings/week increase in chocolate consumption and 0.96 (95% CI 0.90-1.03) for the highest versus lowest category of chocolate consumption. Available data provide no evidence of an association of chocolate consumption with risk of AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between obesity and other risk factors and skin disease among adult Saudi population.

PubMed

Khalil, Ghada M; Al Shobaili, Hani A; Alzolibani, Abdullateef; Al Robaee, Ahmad

2011-01-01

Obesity is accused for a wide spectrum of dermatologic diseases; no previous follow-up study has been conducted to investigate these conditions in adult male and female Saudi population. To describe obesity pattern using BMI and to assess the association between obesity and certain skin diseases among adult Saudi population. A retrospective cohort study of 2-year duration was conducted. The study sample was randomly selected from dermatology clinics at Qassim. Male cohorts were 61 obese adults and 48 nonobese adults. Female cohorts were 32 obese adults and 36 nonobese adults. Measurement of BMI, waist-hip ratio, fasting glucose, blood pressure, and dermatological examination was performed. Skin disease incidence was significantly increased among exposed rather than nonexposed cohorts with a relative risk of 2.3 in male cohort and 2.3 in female cohort. Acanthosis nigricans and striae distensae incidence increased in exposed men and women with highly significant difference from nonexposed groups. Skin tag incidence significantly increased in the exposed male cohorts only but not the female cohort. Hirsutism, dry skin, pruritis, and planter keratosis all showed nonsignificant differences. The most frequently reported infections in obese men were tinea pedis (18%), intertrigo (14.7%), and bacterial folliculitis (13.1%) with significant difference. BMI was the only risk factor that regresses on skin disease occurrence in study groups. Our study linked incidence of acanthosis nigricans and striae distensae to obesity in both female and male adult population but showed sex difference for other skin diseases, which raised many questions and requires further longer duration follow-up studies.

Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: Results from five cohort studies.

PubMed

Fondell, Elinor; O'Reilly, É Ilis J; Fitzgerald, Kathryn C; Falcone, Guido J; Kolonel, Laurence N; Park, Yikyung; Gapstur, Susan M; Ascherio, Alberto

2015-01-01

Caffeine is thought to be neuroprotective by antagonizing the adenosine A2A receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis (ALS). Longitudinal analyses based on over 1,010,000 males and females in five large cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study). Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death were estimated by Cox proportional hazards regression and pooled using random-effects models. Results showed that a total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. In conclusion, the results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk.

Intakes of caffeine, coffee and tea and risk of Amyotrophic Lateral Sclerosis: Results from five cohort studies

PubMed Central

Fondell, Elinor; O'Reilly, Éilis J.; Fitzgerald, Kathryn C.; Falcone, Guido J.; Kolonel, Laurence N.; Park, Yikyung; Gapstur, Susan M.; Ascherio, Alberto

2015-01-01

Objective Caffeine is thought to be neuroprotective by antagonizing the adenosine A2A receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of Amyotrophic Lateral Sclerosis (ALS). Methods Longitudinal analyses based on over 1 010 000 men and women in 5 large cohort studies [the Nurses’ Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health – AARP Diet and Health Study]. Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death was estimated by Cox proportional hazards regression and pooled using random-effects models. Results A total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. Conclusion The results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk. PMID:25822002

Association between diverticular disease and Ehlers-Danlos syndrome: a 13-year nationwide population-based cohort study.

PubMed

Leganger, Julie; Søborg, Marie-Louise Kulas; Mortensen, Laura Quitzau; Gregersen, Rasmus; Rosenberg, Jacob; Burcharth, Jakob

2016-12-01

The aim of this study was to examine occurrence and consequences of diverticular disease in patients with Ehlers-Danlos syndrome (EDS) compared with a matched cohort. This nationwide population-based cohort study was conducted using data from medical registers in Denmark from year 2000 to 2012. The EDS cohort was identified using the specific diagnosis code for EDS and was randomly matched in a ratio of 1:20 by sex and date of birth (±1 year) with persons from the Danish general population. The occurrence of diverticular disease and the clinical characteristics of the initial diverticular event were compared between the EDS cohort and the comparison cohort. The first admission with diverticulitis was identified, and severity of diverticulitis, treatment, colonoscopies, length of stay, and 30-day mortality were investigated. We identified 1336 patients with EDS and matched a control cohort of 26,720 patients. The occurrence of diverticular disease in the EDS cohort (2.0 %) and the comparison cohort (0.68 %) differed significantly (p < 0.001). At the first diverticular event, the majority of patients were women (85 % for EDS and 87 % for the comparison cohort). Mean age, localization, and type of contact did not differ significantly. Admission with diverticulitis (1.0 % for EDS and 0.34 % for the comparison cohort) differed significantly (p < 0.001). We found no significant difference in severity of diverticulitis, treatment, length of stay, or 30-day mortality between the EDS and the comparison cohorts. Patients with EDS had an increased occurrence of overall diverticular events and admissions with diverticulitis compared with the general population.

Multicenter Randomized Controlled Trial on Duration of Therapy for Thrombosis in Children and Young Adults (Kids-DOTT): Pilot/Feasibility Phase Findings

PubMed Central

Goldenberg, N.A.; Abshire, T.; Blatchford, P.J.; Fenton, L.Z.; Halperin, J.L.; Hiatt, W.R.; Kessler, C.M.; Kittelson, J.M.; Manco-Johnson, M.J.; Spyropoulos, A.C.; Steg, P.G.; Stence, N.V.; Turpie, A.G.G.; Schulman, S.

2015-01-01

BACKGROUND Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. RESULTS No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (κ-statistic=0.75; 95% confidence interval [CI] 0.48–1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3–11.5%) and 1.4% (0.03–7.4%). CONCLUSIONS The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. PMID:26118944

Guidelines for the Prevention of Infection After Combat-Related Injuries

DTIC Science & Technology

2008-03-01

randomized con - trol trials or cohort studies that could be incorporated into the guidelines. In addition, civilian trauma articles, primarily randomized...when patients are unable to tolerate oral medication, the TCCC also has pro - vided recommendations for intravenous or intramuscular agents to use in...Level I) is typically provided by a physician assistant or a general medical officer (general med- ical officer ( GMO )—physician with at least 1 year of

Leveraging ongoing research to evaluate the health impacts of South Africa's salt reduction strategy: a prospective nested cohort within the WHO-SAGE multicountry, longitudinal study

PubMed Central

Charlton, Karen; Menyanu, Elias; Biritwum, Richard Berko; Naidoo, Nirmala; Pieterse, Chiné; Madurai, Savathree (Lorna); Baumgartner, Jeannine; Asare, George A; Thiele, Elizabeth; Schutte, Aletta E; Kowal, Paul

2016-01-01

Introduction Attempting to curb the rising epidemic of hypertension, South Africa implemented legislation in June 2016 mandating maximum sodium levels in a range of manufactured foods that contribute significantly to population salt intake. This natural experiment, comparing two African countries with and without salt legislation, will provide timely information on the impact of legislative approaches addressing the food supply to improve blood pressure in African populations. This article outlines the design of this ongoing prospective nested cohort study. Methods and analysis Baseline sodium intake was assessed in a nested cohort of the WHO Study on global AGEing and adult health (WHO-SAGE) wave 2 (2014–2015), a multinational longitudinal study on the health and well-being of adults and the ageing process. The South African cohort consisted of randomly selected households (n=4030) across the country. Spot and 24-hour urine samples are collected in a random subsample (n=1200) and sodium, potassium, creatinine and iodine analysed. Salt behaviour and sociodemographic data are captured using face-to-face interviews, alongside blood pressure and anthropometric measures. Ghana, the selected control country with no formal salt policy, provided a nested subsample (n=1200) contributing spot and 24-hour urine samples from the SAGE Ghana cohort (n=5000). Follow-up interviews and urine collection (wave 3) in both countries will take place in 2017 (postlegislation) to assess change in population-level sodium intake and blood pressure. Ethics and dissemination SAGE was approved by the WHO Ethics Review Committee (reference number RPC149) with local approval from the North-West University Human Research Ethics Committee and University of the Witwatersrand Human Research Ethics Committee (South Africa), and University of Ghana Medical School Ethics and Protocol Review Committee (Ghana). The results of the study will be published in peer-reviewed international journals, presented at national and international conferences, and summarised as research and policy briefs. PMID:27903563

Calculating radiotherapy margins based on Bayesian modelling of patient specific random errors

NASA Astrophysics Data System (ADS)

Herschtal, A.; te Marvelde, L.; Mengersen, K.; Hosseinifard, Z.; Foroudi, F.; Devereux, T.; Pham, D.; Ball, D.; Greer, P. B.; Pichler, P.; Eade, T.; Kneebone, A.; Bell, L.; Caine, H.; Hindson, B.; Kron, T.

2015-02-01

Collected real-life clinical target volume (CTV) displacement data show that some patients undergoing external beam radiotherapy (EBRT) demonstrate significantly more fraction-to-fraction variability in their displacement (‘random error’) than others. This contrasts with the common assumption made by historical recipes for margin estimation for EBRT, that the random error is constant across patients. In this work we present statistical models of CTV displacements in which random errors are characterised by an inverse gamma (IG) distribution in order to assess the impact of random error variability on CTV-to-PTV margin widths, for eight real world patient cohorts from four institutions, and for different sites of malignancy. We considered a variety of clinical treatment requirements and penumbral widths. The eight cohorts consisted of a total of 874 patients and 27 391 treatment sessions. Compared to a traditional margin recipe that assumes constant random errors across patients, for a typical 4 mm penumbral width, the IG based margin model mandates that in order to satisfy the common clinical requirement that 90% of patients receive at least 95% of prescribed RT dose to the entire CTV, margins be increased by a median of 10% (range over the eight cohorts -19% to +35%). This substantially reduces the proportion of patients for whom margins are too small to satisfy clinical requirements.

The Norwegian Healthy Life Study: protocol for a pragmatic RCT with longitudinal follow-up on physical activity and diet for adults.

PubMed

Abildsnes, Eirik; Meland, Eivind; Mildestvedt, Thomas; Stea, Tonje H; Berntsen, Sveinung; Samdal, Gro Beate

2017-01-05

The Norwegian Directorate of Health recommends that Healthy Life Centres (HLCs) be established in primary health care to support behaviour change and reduce the risk of non-communicable diseases. The aim of the present study protocol is to present the rationale, design and methods of a combined pragmatic randomized controlled trial (RCT) and longitudinal cohort study of the effects of attending HLCs concerning physical activity, sedentary behaviour and diet and to explore how psychological well-being and motivational factors may mediate short- and long-term effects. The present study will combine a 6-month RCT with a longitudinal cohort study (24 months from baseline) conducted at six HLCs from June 2014 to Sept 2017. Participants are randomized to behavioural change interventions or a 6-month waiting list control group. A randomized trial of interventions in HLCs has the potential to influence the development of policy and practice for behaviour change interventions and patient education programmes in Norway. We discuss some of the important preconditions for obtaining valid results from a complex intervention and outline some of the characteristics of ecological approaches in health care research that can enable a pragmatic intervention study. The study was retrospectively registered on September 19, 2014 and is available online at ClinicalTrials.gov (ID: NCT02247219 ).

Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

PubMed Central

Chess, James; Do, Jun-Young; Noh, Hyunjin; Lee, Hi-Bahl; Kim, Yong-Lim; Summers, Angela; Williams, Paul Ford; Davison, Sara; Dorval, Marc

2016-01-01

Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. Results The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6–10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34). Conclusions In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses. PMID:27249020

Effects of long-term exposure to traffic-related air pollution on respiratory and cardiovascular mortality in the Netherlands: the NLCS-AIR study.

PubMed

Brunekreef, Bert; Beelen, Rob; Hoek, Gerard; Schouten, Leo; Bausch-Goldbohm, Sandra; Fischer, Paul; Armstrong, Ben; Hughes, Edward; Jerrett, Michael; van den Brandt, Piet

2009-03-01

Evidence is increasing that long-term exposure to ambient air pollution is associated with deaths from cardiopulmonary diseases. In a 2002 pilot study, we reported clear indications that traffic-related air pollution, especially at the local scale, was related to cardiopulmonary mortality in a randomly selected subcohort of 5000 older adults participating in the ongoing Netherlands Cohort Study (NLCS) on diet and cancer. In the current study, referred to as NLCS-AIR, our objective was to obtain more precise estimates of the effects of traffic-related air pollution by analyzing associations with cause-specific mortality, as well as lung cancer incidence, in the full cohort of approximately 120,000 subjects. Cohort members were 55 to 69 years of age at enrollment in 1986. Follow-up was from 1987 through 1996 for mortality (17,674 deaths) and from late 1986 through 1997 for lung cancer incidence (2234 cases). Information about potential confounding variables and effect modifiers was available from the questionnaire that subjects completed at enrollment and from publicly available data (including neighborhood-scale information such as income distributions). The NLCS was designed for a case-cohort approach, which makes use of all the cases in the full cohort, while data for the random subcohort are used to estimate person-time experience in the study. Full information on confounders was available for the subjects in the random subcohort and for the emerging cases of mortality and lung cancer incidence during the follow-up period, and in NLCS-AIR we used the case-cohort approach to examine the relation between exposure to air pollution and cause-specific mortality and lung cancer. We also specified a standard Cox proportional hazards model within the full cohort, for which information on potential confounding variables was much more limited. Exposure to air pollution was estimated for the subjects' home addresses at baseline in 1986. Concentrations were estimated for black smoke (a simple marker for soot) and nitrogen dioxide (NO2) as indicators of traffic-related air pollution, as well as nitric oxide (NO), sulfur dioxide (SO2), and particulate matter with aerodynamic diameter < or = 2.5 microm (PM2.5), as estimated from measurements of particulate matter with aerodynamic diameter < or = 10 microm (PM10). Overall long-term exposure concentrations were considered to be a function of air pollution contributions at regional, urban, and local scales. We used interpolation from data obtained routinely at regional stations of the National Air Quality Monitoring Network (NAQMN) to estimate the regional component of exposure at the home address. Average pollutant concentrations were estimated from NAQMN measurements for the period 1976 through 1996. Land-use regression methods were used to estimate the urban exposure component. For the local exposure component, geographic information systems (GISs) were used to generate indicators of traffic exposure that included traffic intensity on and distance to nearby roads. A major effort was made to collect traffic intensity data from individual municipalities. The exposure variables were refined considerably from those used in the pilot study, but we also analyzed the data for the full cohort in the current study using the exposure indicators of the pilot study. We analyzed the data in models with the estimated overall pollutant concentration as a single variable and with the background concentration (the sum of regional and urban components) and the local exposure estimate from traffic indicators as separate variables. In the full-cohort analyses adjusted for the limited set of confounders, estimated overall exposure concentrations of black smoke, NO2, NO, and PM2.5 were associated with mortality. For a 10-microg/m3 increase in the black smoke concentration, the relative risk (RR) (95% confidence interval [CI]) was 1.05 (1.00-1.11) for natural-cause (nonaccidental) mortality, 1.04 (0.95-1.13) for cardiovascular mortality, 1.22 (0.99-1.50) for respiratory mortality, 1.03 (0.88-1.20) for lung cancer mortality, and 1.04 (0.97-1.12) for noncardiopulmonary, non-lung cancer mortality. Results were similar for NO2, NO, and PM2.5. For a 10-microg/m3 increase in PM2.5 concentration, the RR for natural-cause mortality was 1.06 (95% CI, 0.97-1.16), the same as in the results of the American Cancer Society Study reported by Pope and colleagues in 2002. The highest relative risks were found for respiratory mortality, though confidence intervals were wider for this less-frequent cause of death. No associations with mortality were found for SO2. Some of the associations between the traffic indicator variables used to assess traffic intensity near the home and mortality reached statistical significance in the full cohort. For an increase in traffic intensity of 10,000 motor vehicles in 24 hours (motor vehicles/day) on the road nearest a subject's residence, the RR was 1.03 (95% CI, 1.00-1.08) for natural-cause mortality, 1.05 (0.99-1.12) for cardiovascular mortality, 1.10 (0.95-1.26) for respiratory mortality, 1.07 (0.96-1.19) for lung cancer mortality, and 1.00 (0.94-1.06) for noncardiopulmonary, non-lung cancer mortality. Results were similar for traffic intensity in a 100-m buffer around the subject's residence and living near a major road (a road with more than 10,000 motor vehicles/day). Distance in meters to the nearest major road and traffic intensity on the nearest major road were not associated with any of the mortality outcomes. We did not find an association between cardiopulmonary mortality and living near a major road as defined using the methods of the pilot study. In the case-cohort analyses adjusted for all potential confounders, we found no associations between background air pollution and mortality. The associations between traffic intensity and mortality were weaker than in the full cohort, and confidence intervals were wider, consistent with the smaller number of subjects. The lower relative risks of mortality associated with traffic variables in the case-cohort study population could be related to the particular subcohort that was randomly selected from the full cohort, as the risks estimated with the actual subcohort were well below the average estimates obtained for 100 new case-cohort analyses with 100 alternative subcohorts of 5000 subjects each that we randomly selected from the full cohort. Differences in adjusted relative risks between the full-cohort and the case-cohort analyses could be explained by random error introduced by sampling from the full cohort and by a selection effect resulting from the relatively large number of missing data for variables in the extensive confounder model used in the case-cohort analyses. More complete control for confounding probably did not contribute much to the lower relative risks in the case-cohort analyses, especially for the traffic variables, as results were similar when the limited confounder model for the full cohort was used in analyses of the subjects in the case-cohort study population. In additional analyses using black smoke concentrations as the exposure variables, we found that the association between overall black smoke and cardiopulmonary mortality was somewhat stronger for case-cohort subjects who did not change residence during follow-up, and in the full cohort, there was a tendency for relative risks to be higher for subjects living in the three major cities included in the study. Adjustment for estimated exposure to traffic noise did not affect the associations of background black smoke and traffic intensity with cardiovascular mortality. There was some indication of an association between traffic noise and cardiovascular mortality only for the 1.6% of the subjects in the full cohort who were exposed to traffic noise in the highest category of > 65 A-weighted decibels (dB(A); decibels with the sound pressure scale adjusted to conform with the frequency response of the human ear). Examination of sex, smoking status, educational level, and vegetable and fruit intake as possible effect modifiers showed that for overall black smoke concentrations, associations with mortality tended to be stronger in case-cohort subjects with lower levels of education and those with low fruit intake, but differences between strata were not statistically significant. For lung cancer incidence, we found essentially no relation to exposure to NO2, black smoke, PM2.5, SO2, or several traffic indicators. Associations of overall air pollution concentrations and traffic indicator variables with lung cancer incidence were, however, found in subjects who had never smoked, with an RR of 1.47 (95% CI, 1.01-2.16) for a 10-microg/m3 increase in overall black smoke concentration. In the current study, the mortality risks associated with both background air pollution and traffic exposure variables were much smaller than the estimate previously reported in the pilot study for risk of cardiopulmonary mortality associated with living near a major road (RR, 1.95; 95% CI, 1.09-3.51). The differences are most likely due to the extension of the follow-up period in the current study and to random error in the pilot study related to sampling from the full cohort. Though relative risks were generally small in the current study, long-term average concentrations of black smoke, NO2, and PM2.5 were related to mortality, and associations of black smoke and NO2 exposure with natural-cause and respiratory mortality were statistically significant. Traffic intensity near the home was also related to natural-cause mortality. The highest relative risks associated with background air pollution and traffic variables were for respiratory mortality, though the number of deaths was smaller than for the other mortality categories. (ABSTRACT TRUNCATED)

Prognosis of acute idiopathic neck pain is poor: a systematic review and meta-analysis.

PubMed

Hush, Julia M; Lin, C Christine; Michaleff, Zoe A; Verhagen, Arianne; Refshauge, Kathryn M

2011-05-01

To conduct a systematic review and meta-analysis on the prognosis of acute idiopathic neck pain and disability. EMBASE, CINAHL, Medline, AMED, PEDro, and CENTRAL were searched from inception to July 2009, limited to human studies. Reference lists of relevant systematic reviews were searched by hand. Search terms included: neck pain, prognosis, inception, cohort, longitudinal, observational, or prospective study and randomized controlled trial. Eligible studies were longitudinal cohort studies and randomized controlled trials with a no treatment or minimal treatment arm that recruited an inception cohort of acute idiopathic neck pain and reported pain or disability outcomes. Eligibility was determined by 2 authors independently. Seven of 20,085 references were included. Pain and disability data were extracted independently by 2 authors. Risk of bias was assessed independently by 2 authors. Statistical pooling showed a weighted mean pain score (0-100) of 64 (95% confidence interval [CI], 61-67) at onset and 35 (95% CI, 32-38) at 6.5 weeks. At 12 months, neck pain severity remained high at 42 (95% CI, 39-45). Disability reduced from a pooled weighted mean score (0-100) at onset of 30 (95% CI, 28-32) to 17 (95% CI, 15-19) by 6.5 weeks, without further improvement at 12 months. Studies varied in length of follow-up, design, and sample size. This review provides Level I evidence that the prognosis of acute idiopathic neck pain is worse than currently recognized. This evidence can guide primary care clinicians when providing prognostic information to patients. Further research to identify prognostic factors and long-term outcomes from inception cohorts would be valuable. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Fruit and vegetables consumption and incident hypertension: dose-response meta-analysis of prospective cohort studies.

PubMed

Wu, L; Sun, D; He, Y

2016-10-01

The role of dietary factors on chronic diseases seems essential in the potentially adverse or preventive effects. However, no evidence of dose-response meta-analysis of prospective cohort studies has verified the association between the intake of fruit and/or vegetables and the risk of developing hypertension. The PubMed and Embase were searched for prospective cohort studies. A generic inverse-variance method with random effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Generalized least squares trend estimation model was used to calculate the study-specific slopes for the dose-response analyses. Seven articles comprised nine cohorts involving 185 676 participants were assessed. The highest intake of fruit or vegetables separately, and total fruit and vegetables were inversely associated with the incident risk of hypertension compared with the lowest level, and the pooled RRs and 95% CIs were 0.87 (0.79, 0.95), 0.88 (0.79, 0.99) and 0.90 (0.84, 0.98), respectively. We also found an inverse dose-response relation between the risk of developing hypertension and fruit intake, and total fruit and vegetables consumption. The incident risk of hypertension was decreased by 1.9% for each serving per day of fruit consumption, and decreased by 1.2% for each serving per day of total fruit and vegetables consumption. Our results support the recommendation to increase the consumption of fruit and vegetables with respect to preventing the risk of developing hypertension. However, further large prospective studies and long-term high-quality randomized controlled trials are still needed to confirm the observed association.

Analysis of cohort studies with multivariate and partially observed disease classification data.

PubMed

Chatterjee, Nilanjan; Sinha, Samiran; Diver, W Ryan; Feigelson, Heather Spencer

2010-09-01

Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort.

Impact of operation details on hydrocephalus after decompressive craniectomy

PubMed Central

Wang, Qiang-Ping; Ma, Jun-Peng; Zhou, Zhang-Ming; You, Chao

2016-01-01

Objective: To evaluate the correlation between the distance of craniectomy from the midline and hydrocephalus after DC. Methods: The following electronic databases were searched from their inception to June 2015: Cochrane Library, MEDLINE, Science Direct, EMBASE, Scopus, Google Scholar, the Chinese Biomedical Database (CBM), and the Chinese National Knowledge Infrastructure (CNKI). All randomized clinical trials, prospective cohort, retrospective observational cohort, and case-control studies investigating the relationship between distance of craniectomy from the midline and hydrocephalus after DC were enrolled. The Cochrane Collaboration’s software RevMan 5.3 was used for meta-analysis. Results: Six retrospective cohort studies involving 462 participants were included. Pooled analysis of 4 studies suggested that craniectomy close to the midline (<25 mm) was associated with a significantly increased risk of postoperative hydrocephalus (odds ratio [OR] = 3.61, 95% confidence interval [CI]: 1.3 - 9.97, p=0.01). However, meta-analysis of 4 studies did not find statistical differences when comparing the distance of craniectomy from the midline in the hydrocephalus group and that in the non-hydrocephalus group (OR = −0.14, 95% CI: −0.44 - 0.15, p=0.34). Conclusions: Available evidence was insufficient to support the theory that craniectomy close to the midline increases the risk of developing hydrocephalus after DC. Well-conducted randomized clinical trials are required to verify this issue. PMID:26818161

Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study--secondary analysis of the randomized trial.

PubMed

Uusitupa, Matti; Peltonen, Markku; Lindström, Jaana; Aunola, Sirkka; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Valle, Timo T; Eriksson, Johan G; Tuomilehto, Jaakko

2009-05-21

The Finnish Diabetes Prevention Study (DPS) was a randomized controlled trial, which showed that it is possible to prevent type 2 diabetes by lifestyle changes. The aim of the present study was to examine whether the lifestyle intervention had an effect on the ten-year mortality and cardiovascular morbidity in the DPS participants originally randomized either into an intervention or control group. Furthermore, we compared these results with a population-based cohort comprising individuals of varying glucose tolerance states. Middle-aged, overweight people with IGT (n = 522) were randomized into intensive intervention (including physical activity, weight reduction and dietary counseling), or control "mini-intervention" group. Median length of the intervention period was 4 years and the mean follow-up was 10.6 years. The population-based reference study cohort included 1881 individuals (1570 with normal glucose tolerance, 183 with IGT, 59 with screen-detected type 2 diabetes, 69 with previously known type 2 diabetes) with the mean follow-up of 13.8 years. Mortality and cardiovascular morbidity data were collected from the national Hospital Discharge Register and Causes of Death Register. Among the DPS participants who consented for register linkage (n = 505), total mortality (2.2 vs. 3.8 per 1000 person years, hazard ratio HR = 0.57, 95% CI 0.21-1.58) and cardiovascular morbidity (22.9 vs. 22.0 per 1000 person years, HR = 1.04, 95% CI 0.72-1.51) did not differ significantly between the intervention and control groups. Compared with the population-based cohort with impaired glucose tolerance, adjusted HRs were 0.21 (95% CI 0.09-0.52) and 0.39 (95% CI 0.20-0.79) for total mortality, and 0.89 (95% CI 0.62-1.27) and 0.87 (0.60-1.27) for cardiovascular morbidity in the intervention and control groups of the DPS, respectively. The risk of death in DPS combined cohort was markedly lower than in FINRISK IGT cohort (adjusted HR 0.30, 95% CI 0.17-0.54), but there was no significant difference in the risk of CVD (adjusted HR 0.88, 95% CI 0.64-1.21). Lifestyle intervention among persons with IGT did not decrease cardiovascular morbidity during the first 10 years of follow-up. However, the statistical power may not be sufficient to detect small differences between the intervention and control groups. Low total mortality among participants of the DPS compared with individuals with IGT in the general population could be ascribed to a lower cardiovascular risk profile at baseline and regular follow-up. ClinicalTrials.gov NCT00518167.

Efficacy of Multivitamin/mineral Supplementation to Reduce Chronic Disease Risk: A Critical Review of the Evidence from Observational Studies and Randomized Controlled Trials.

PubMed

Angelo, Giana; Drake, Victoria J; Frei, Balz

2015-01-01

We reviewed recent scientific evidence regarding the effects of multivitamin/mineral (MVM) supplements on risk of chronic diseases, including cancer, cardiovascular disease, and age-related eye diseases. Data from randomized controlled trials (RCTs) and observational, prospective cohort studies were examined. The majority of scientific studies investigating the use of MVM supplements in chronic disease risk reduction reported no significant effect. However, the largest and longest RCT of MVM supplements conducted to date, the Physicians' Health Study II (PHS II), found a modest and significant reduction in total and epithelial cancer incidence in male physicians, consistent with the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) trial. In addition, PHS II found a modest and significant reduction in the incidence of nuclear cataract, in agreement with several other RCTs and observational, prospective cohort studies. The effects of MVM use on other subtypes of cataract and age-related macular degeneration remain unclear. Neither RCTs nor prospective cohort studies are without their limitations. The placebo-controlled trial design of RCTs may be inadequate for nutrient interventions, and residual confounding, measurement error, and the possibility of reverse causality are inherent to any observational study. National surveys show that micronutrient inadequacies are widespread in the US and that dietary supplements, of which MVMs are the most common type, help fulfill micronutrient requirements in adults and children.

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals†

PubMed Central

Rivera, Margarita; Locke, Adam E.; Corre, Tanguy; Czamara, Darina; Wolf, Christiane; Ching-Lopez, Ana; Milaneschi, Yuri; Kloiber, Stefan; Cohen-Woods, Sara; Rucker, James; Aitchison, Katherine J.; Bergmann, Sven; Boomsma, Dorret I.; Craddock, Nick; Gill, Michael; Holsboer, Florian; Hottenga, Jouke-Jan; Korszun, Ania; Kutalik, Zoltan; Lucae, Susanne; Maier, Wolfgang; Mors, Ole; Müller-Myhsok, Bertram; Owen, Michael J.; Penninx, Brenda W. J. H.; Preisig, Martin; Rice, John; Rietschel, Marcella; Tozzi, Federica; Uher, Rudolf; Vollenweider, Peter; Waeber, Gerard; Willemsen, Gonneke; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; Breen, Gerome; McGuffin, Peter

2017-01-01

Background Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT. Results In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO. Conclusions This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression. PMID:28642257

Regional or general anesthesia for fast-track hip and knee replacement - what is the evidence?

PubMed Central

Kehlet, Henrik; Aasvang, Eske Kvanner

2015-01-01

Regional anesthesia for knee and hip arthroplasty may have favorable outcome effects compared with general anesthesia by effectively blocking afferent input, providing initial postoperative analgesia, reducing endocrine metabolic responses, and providing sympathetic blockade with reduced bleeding and less risk of thromboembolic complications but with undesirable effects on lower limb motor and urinary bladder function. Old randomized studies supported the use of regional anesthesia with fewer postoperative pulmonary and thromboembolic complications, and this has been supported by recent large non-randomized epidemiological database cohort studies. In contrast, the data from newer randomized trials are conflicting, and recent studies using modern general anesthetic techniques may potentially support the use of general versus spinal anesthesia. In summary, the lack of properly designed large randomized controlled trials comparing modern general anesthesia and spinal anesthesia for knee and hip arthroplasty prevents final recommendations and calls for prospective detailed studies in this clinically important field. PMID:26918127

Do children with grapheme-colour synaesthesia show cognitive benefits?

PubMed

Simner, Julia; Bain, Angela E

2018-02-01

Grapheme-colour synaesthesia is characterized by conscious and consistent associations between letters and colours, or between numbers and colours (e.g., synaesthetes might see A as red, 7 as green). Our study explored the development of this condition in a group of randomly sampled child synaesthetes. Two previous studies (Simner & Bain, 2013, Frontiers in Human Neuroscience, 7, 603; Simner, Harrold, Creed, Monro, & Foulkes, 2009, Brain, 132, 57) had screened over 600 primary school children to find the first randomly sampled cohort of child synaesthetes. In this study, we evaluate this cohort to ask whether their synaesthesia is associated with a particular cognitive profile of strengths and/or weaknesses. We tested our child synaesthetes at age 10-11 years in a series of cognitive tests, in comparison with matched controls and baseline norms. One previous study (Green & Goswami, 2008, Cognition, 106, 463) had suggested that child synaesthetes might perform differently to non-synaesthetes in such tasks, although those participants may have been a special type of population independent of their synaesthesia. In our own study of randomly sampled child synaesthetes, we found no significant advantages or disadvantages in a receptive vocabulary test and a memory matrix task. However, we found that synaesthetes demonstrated above-average performance in a processing-speed task and a near-significant advantage in a letter-span task (i.e., memory/recall task of letters). Our findings point to advantages for synaesthetes that go beyond those expected from enhanced coding accounts and we present the first picture of the broader cognitive profile of a randomly sampled population of child synaesthetes. © 2017 The British Psychological Society.

Risk of Endophthalmitis and Other Long-Term Complications of Trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS)

PubMed Central

Zahid, Sarwar; Musch, David C.; Niziol, Leslie M.; Lichter, Paul R.

2012-01-01

Purpose To report the risk of endophthalmitis and other long-term complications in patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Design A longitudinal cohort study using data collected from a multicenter, randomized clinical trial. Methods Long-term post-operative complications in the 300 patients randomized to trabeculectomy in CIGTS were tabulated. Kaplan-Meier analyses were used to estimate the time-related probability of blebitis, hypotony, and endophthalmitis. Results 285 patients were included in the final trabeculectomy cohort after accounting for assignment refusal and other early events. Patients were followed for an average of 7.2 years. 163 patients (57%) received 5-fluorouracil (5-FU) intraoperatively. Of the 247 patients with at least 5 years of follow-up, 50 required further treatment for glaucoma. Cataract extraction was performed in 57 patients (20%). Forty patients (14%) required bleb revision at least once. Bleb-related complications included bleb leak (N = 15), blebitis (N = 8), and hypotony (N = 4). Three patients were noted to have endophthalmitis, although the diagnosis in two patients was presumptive. The occurrences of blebitis, hypotony, or endophthalmitis were not significantly associated with 5-FU use. The Kaplan-Meier calculated risks of blebitis and hypotony at 5 years were both 1.5%, while the risk of endophthalmitis was 1.1%. Conclusions The potential efficacy of trabeculectomy must be weighed against the long-term risk of complications, especially endophthalmitis, when selecting treatments for patients with open-angle glaucoma. We report a low 5-year risk of endophthalmitis (1.1%) and other bleb-related complications in the trabeculectomy cohort of the CIGTS. PMID:23246272

Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure.

PubMed

Bostom, Andrew; Steubl, Dominik; Garimella, Pranav S; Franceschini, Nora; Roberts, Mary B; Pasch, Andreas; Ix, Joachim H; Tuttle, Katherine R; Ivanova, Anastasia; Shireman, Theresa; Kim, S Joseph; Gohh, Reginald; Weiner, Daniel E; Levey, Andrew S; Hsu, Chi-Yuan; Kusek, John W; Eaton, Charles B

2018-01-01

Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs. © 2018 S. Karger AG, Basel.

Effects of a laboratory-based skills curriculum on laparoscopic proficiency: a randomized trial.

PubMed

Coleman, Robert L; Muller, Carolyn Y

2002-04-01

The purpose of this study was to determine the effect and validity of an intensive laboratory-based laparoscopic skills training curriculum on operative proficiency in obstetrics and gynecology residents. This was a prospective, randomized, block-design trial of postgraduate year 3 and 4 residents. The following study schedule was used: week 1 (pre-randomization) included an orientation to study objectives, the administration of a laparoscopic experience questionnaire, timed video-laparoscopic drills (5 total), and the performance of a video-recorded laparoscopic partial salpingectomy; during weeks 2 and 3, the skills group residents repeated the laparoscopic drills 30 minutes daily for 10 days, and the control group residents had no formal practice sessions; during week 4, the week 1 evaluation was repeated. Operative proficiency was quantified by the Global Skills Assessment Tool through blinded, independent scoring of videotapes. Twenty-six residents (skills group, 12; control group, 14) consented to the trial. Patient-related issues excluded 8 residents (30%). At week 1, no significant differences existed in previous laparoscopic experience, timed video skills, or resident operative proficiency (Global Skills Assessment Tool score) between cohorts. At week 4, both groups significantly improved their timed drill test scores. The percent reduction in time from baseline was of greater magnitude in the skills group versus control group (51% vs 18%,P <.0001). Laparoscopic performance also improved in both cohorts (P =.002). However, only the skills group demonstrated significant intra-cohort improvement from baseline (mean, 4.9 points; P =.015; 95% CI, 1-7.5). A core curriculum of intensive video laparoscopic skills training improves not only technical but also operative performance among postgraduate year 3 and 4 residents.

Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study

PubMed Central

Handley, Alison; Lloyd, Eric; Roberts, Andrew; Barger, Bruce

2016-01-01

Abstract This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5–25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics. PMID:26817604

Allgöwer-Donati Versus Vertical Mattress Suture Technique Impact on Perfusion in Ankle Fracture Surgery: A Randomized Clinical Trial Using Intraoperative Angiography.

PubMed

Shannon, Steven F; Houdek, Matthew T; Wyles, Cody C; Yuan, Brandon J; Cross, William W; Cass, Joseph R; Sems, Stephen A

2017-02-01

The purpose of this study was to evaluate which primary wound closure technique for ankle fractures affords the most robust perfusion as measured by laser-assisted indocyanine green angiography: Allgöwer-Donati or vertical mattress. Prospective, randomized. Level 1 Academic Trauma Center. Thirty patients undergoing open reduction internal fixation for ankle fractures were prospectively randomized to Allgöwer-Donati (n = 15) or vertical mattress (n = 15) closure. Demographics were similar for both cohorts with respect to age, sex, body mass index, surgical timing, and OTA/AO fracture classification. Skin perfusion (mean incision perfusion and mean perfusion impairment) was quantified in fluorescence units with laser-assisted indocyanine green angiography along the lateral incision as well as anterior and posterior to the incision at 30 separate locations. Minimum follow-up was 3 months with a mean follow-up 4.7 months. Allgöwer-Donati enabled superior perfusion compared with the vertical mattress suture technique. Mean incision perfusion for Allgöwer-Donati was 51 (SD = 13) and for vertical mattress was 28 (SD = 10, P < 0.0001). Mean perfusion impairment was less in the Allgöwer-Donati cohort (12.8, SD = 9) compared with that in the vertical mattress cohort (23.4, SD = 14; P = 0.03). One patient in each cohort experienced a wound complication. The Allgöwer-Donati suture technique offers improved incision perfusion compared with vertical mattress closure after open reduction internal fixation of ankle fractures. Theoretically, this may enhance soft tissue healing and decrease the risk of wound complications. Surgeons may take this into consideration when deciding closure techniques for ankle fractures. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Vitamin D status and the risk of type 2 diabetes: the Melbourne Collaborative Cohort Study.

PubMed

Heath, Alicia K; Williamson, Elizabeth J; Hodge, Allison M; Ebeling, Peter R; Eyles, Darryl W; Kvaskoff, David; O'Dea, Kerin; Giles, Graham G; English, Dallas R

2018-05-18

Inverse associations between vitamin D status and risk of type 2 diabetes observed in epidemiological studies could be biased by confounding and reverse causality. We investigated the prospective association between vitamin D status and type 2 diabetes and the possible role of reverse causality. We conducted a case-cohort study within the Melbourne Collaborative Cohort Study (MCCS), including a random sample of 628 participants who developed diabetes and a sex-stratified random sample of the cohort (n=1,884). Concentration of 25-hydroxyvitamin D (25(OH)D) was measured using liquid chromatography-tandem mass spectrometry in samples collected at recruitment. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of type 2 diabetes for quartiles of 25(OH)D relative to the lowest quartile and per 25 nmol/L increase in 25(OH)D, adjusting for confounding variables. The ORs for the highest versus lowest 25(OH)D quartile and per 25 nmol/L increase in 25(OH)D were 0.60 (95% CI: 0.44, 0.81) and 0.76 (95% CI: 0.63, 0.92; p=0.004), respectively. In participants who reported being in good/very good/excellent health approximately four years after recruitment, ORs for the highest versus lowest 25(OH)D quartile and per 25 nmol/L increase in 25(OH)D were 0.46 (95% CI: 0.29, 0.72) and 0.71 (95% CI: 0.56, 0.89; p=0.003), respectively. In this sample of middle-aged Australians, vitamin D status was inversely associated with the risk of type 2 diabetes, and this association did not appear to be explained by reverse causality. Copyright © 2018. Published by Elsevier B.V.

Cultivating cohort studies for observational translational research.

PubMed

Ransohoff, David F

2013-04-01

"Discovery" research about molecular markers for diagnosis, prognosis, or prediction of response to therapy has frequently produced results that were not reproducible in subsequent studies. What are the reasons, and can observational cohorts be cultivated to provide strong and reliable answers to those questions? Experimental Selected examples are used to illustrate: (i) what features of research design provide strength and reliability in observational studies about markers of diagnosis, prognosis, and response to therapy? (ii) How can those design features be cultivated in existing observational cohorts, for example, within randomized controlled clinical trial (RCT), other existing observational research studies, or practice settings like health maintenance organization (HMOs)? Examples include a study of RNA expression profiles of tumor tissue to predict prognosis of breast cancer, a study of serum proteomics profiles to diagnose ovarian cancer, and a study of stool-based DNA assays to screen for colon cancer. Strengths and weaknesses of observational study design features are discussed, along with lessons about how features that help assure strength might be "cultivated" in the future. By considering these examples and others, it may be possible to develop a process of "cultivating cohorts" in ongoing RCTs, observational cohort studies, and practice settings like HMOs that have strong features of study design. Such an effort could produce sources of data and specimens to reliably answer questions about the use of molecular markers in diagnosis, prognosis, and response to therapy.

Dietary Cholesterol Intake and Risk of Lung Cancer: A Meta-Analysis.

PubMed

Lin, Xiaojing; Liu, Lingli; Fu, Youyun; Gao, Jing; He, Yunyun; Wu, Yang; Lian, Xuemei

2018-02-08

Multiple epidemiologic studies have evaluated the relationship between dietary cholesterol and lung cancer risk, but the association is controversial and inconclusive. A meta-analysis of case-control studies and cohort studies was conducted to evaluate the relationship between dietary cholesterol intake and lung cancer risk in this study. A relevant literature search up to October 2017 was performed in Web of Science, PubMed, China National Knowledge Infrastructure, Sinomed, and VIP Journal Integration Platform. Ten case-control studies and six cohort studies were included in the meta-analysis, and the risk estimates were pooled using either fixed or random effects models. The case-control studies with a total of 6894 lung cancer cases and 29,736 controls showed that dietary cholesterol intake was positively associated with lung cancer risk (Odds Ratio = 1.70, 95% Confidence Interval: 1.43-2.03). However, there was no evidence of an association between dietary cholesterol intake and risk of lung cancer among the 241,920 participants and 1769 lung cancer cases in the cohort studies (Relative Risk = 1.08, 95% Confidence Interval: 0.94-1.25). Due to inconsistent results from case-control and cohort studies, it is difficult to draw any conclusion regarding the effects of dietary cholesterol intake on lung cancer risk. Carefully designed and well-conducted cohort studies are needed to identify the association between dietary cholesterol and lung cancer risk.

Parent-Infant Vocalisations at 12 Months Predict Psychopathology at 7 Years

ERIC Educational Resources Information Center

Allely, C. S.; Purves, D.; McConnachie, A.; Marwick, H.; Johnson, P.; Doolin, O.; Puckering, C.; Golding, J.; Gillberg, C.; Wilson, P.

2013-01-01

This study investigated the utility of adult and infant vocalisation in the prediction of child psychopathology. Families were sampled from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Vocalisation patterns were obtained from 180 videos (60 cases and 120 randomly selected sex-matched controls) of parent-infant…

The Role of Advanced High School Coursework in Increasing STEM Career Interest

ERIC Educational Resources Information Center

Sadler, Philip M.; Sonnert, Gerhard; Hazari, Zahra; Tai, Robert

2014-01-01

Several avenues are open to students who wish to study advanced science or mathematics in high school, which include Advanced Placement courses and teacher-designed courses unaffiliated with organized programs. We employ a retrospective cohort study of 4,691 nationally representative college students at 34 randomly selected, colleges and…

Increased appropriateness of customized alert acknowledgement reasons for overridden medication alerts in a computerized provider order entry system.

PubMed

Dekarske, Brian M; Zimmerman, Christopher R; Chang, Robert; Grant, Paul J; Chaffee, Bruce W

2015-12-01

Computerized provider order entry systems commonly contain alerting mechanisms for patient allergies, incorrect doses, or drug-drug interactions when ordering medications. Providers have the option to override (bypass) these alerts and continue with the order unchanged. This study examines the effect of customizing medication alert override options on the appropriateness of override selection related to patient allergies, drug dosing, and drug-drug interactions when ordering medications in an electronic medical record. In this prospective, randomized crossover study, providers were randomized into cohorts that required a reason for overriding a medication alert from a customized or non-customized list of override reasons and/or by free-text entry. The primary outcome was to compare override responses that appropriately correlate with the alert type between the customized and non-customized configurations. The appropriateness of a subset of free-text responses that represented an affirmative and active acknowledgement of the alert without further explanation was classified as "indeterminate." Results were analyzed in three different ways by classifying indeterminate answers as either appropriate, inappropriate, or excluded entirely. Secondary outcomes included the appropriateness of override reasons when comparing cohorts and individual providers, reason selection based on order within the override list, and the determination of the frequency of free-text use, nonsensical responses, and multiple selection responses. Twenty-two clinicians were randomized into 2 cohorts and a total of 1829 alerts with a required response were generated during the study period. The customized configuration had a higher rate of appropriateness when compared to the non-customized configuration regardless of how indeterminate responses were classified (p<0.001). When comparing cohorts, appropriateness was significantly higher in the customized configuration regardless of the classification of indeterminate responses (p<0.001) with one exception: when indeterminate responses were considered inappropriate for the cohort of providers that were first exposed to the non-customized list (p=0.103). Free-text use was higher in the customized configuration overall (p<0.001), and there was no difference in nonsensical response between configurations (p=0.39). There is a benefit realized by using a customized list for medication override reasons. Poor application design or configuration can negatively affect provider behavior when responding to important medication alerts. Copyright © 2015. Published by Elsevier Ireland Ltd.

Using social-emotional and character development to improve academic outcomes: a matched-pair, cluster-randomized controlled trial in low-income, urban schools

PubMed Central

Lewis, Kendra M.; DuBois, David L.; Acock, Alan; Vuchinich, Samuel; Silverthorn, Naida; Snyder, Frank J.; Day, Joseph; Ji, Peter; Flay, Brian R.

2013-01-01

BACKGROUND School-based social-emotional and character development (SECD) programs can influence not only SECD, but also academic-related outcomes. This study evaluated the impact of one SECD program, Positive Action (PA), on educational outcomes among low-income, urban youth. METHODS The longitudinal study used a matched-pair, cluster-randomized controlled design. Student-reported disaffection with learning and academic grades, and teacher ratings of academic ability and motivation were assessed for a cohort followed from grades 3 to 8. Aggregate school records were used to assess standardized test performance (for entire school, cohort, and demographic subgroups) and absenteeism (entire school). Multilevel growth-curve analyses tested program effects. RESULTS PA significantly improved growth in academic motivation and mitigated disaffection with learning. There was a positive impact of PA on absenteeism and marginally significant impact on math performance of all students. There were favorable program effects on reading for African American boys and cohort students transitioning between grades 7 and 8, and on math for girls and low-income students. CONCLUSIONS A school-based SECD program was found to influence academic outcomes among students living in low-income, urban communities. Future research should examine mechanisms by which changes in SECD influence changes in academic outcomes. PMID:24138347

Using social-emotional and character development to improve academic outcomes: a matched-pair, cluster-randomized controlled trial in low-income, urban schools.

PubMed

Bavarian, Niloofar; Lewis, Kendra M; Dubois, David L; Acock, Alan; Vuchinich, Samuel; Silverthorn, Naida; Snyder, Frank J; Day, Joseph; Ji, Peter; Flay, Brian R

2013-11-01

School-based social-emotional and character development (SECD) programs can influence not only SECD but also academic-related outcomes. This study evaluated the impact of one SECD program, Positive Action (PA), on educational outcomes among low-income, urban youth. The longitudinal study used a matched-pair, cluster-randomized controlled design. Student-reported disaffection with learning and academic grades, and teacher ratings of academic ability and motivation were assessed for a cohort followed from grades 3 to 8. Aggregate school records were used to assess standardized test performance (for entire school, cohort, and demographic subgroups) and absenteeism (entire school). Multilevel growth-curve analyses tested program effects. PA significantly improved growth in academic motivation and mitigated disaffection with learning. There was a positive impact of PA on absenteeism and marginally significant impact on math performance of all students. There were favorable program effects on reading for African American boys and cohort students transitioning between grades 7 and 8, and on math for girls and low-income students. A school-based SECD program was found to influence academic outcomes among students living in low-income, urban communities. Future research should examine mechanisms by which changes in SECD influence changes in academic outcomes. © 2013, American School Health Association.

Assessment of fracture risk: value of random population-based samples--the Geelong Osteoporosis Study.

PubMed

Henry, M J; Pasco, J A; Seeman, E; Nicholson, G C; Sanders, K M; Kotowicz, M A

2001-01-01

Fracture risk is determined by bone mineral density (BMD). The T-score, a measure of fracture risk, is the position of an individual's BMD in relation to a reference range. The aim of this study was to determine the magnitude of change in the T-score when different sampling techniques were used to produce the reference range. Reference ranges were derived from three samples, drawn from the same region: (1) an age-stratified population-based random sample, (2) unselected volunteers, and (3) a selected healthy subset of the population-based sample with no diseases or drugs known to affect bone. T-scores were calculated using the three reference ranges for a cohort of women who had sustained a fracture and as a group had a low mean BMD (ages 35-72 yr; n = 484). For most comparisons, the T-scores for the fracture cohort were more negative using the population reference range. The difference in T-scores reached 1.0 SD. The proportion of the fracture cohort classified as having osteoporosis at the spine was 26, 14, and 23% when the population, volunteer, and healthy reference ranges were applied, respectively. The use of inappropriate reference ranges results in substantial changes to T-scores and may lead to inappropriate management.

Self-Reported Functional Status among the Old-Old: A Comparison of Two Israeli Cohorts

PubMed Central

Litwin, Howard; Shrira, Amit; Shmotkin, Dov

2012-01-01

OBJECTIVES To examine differences in functional status among two successive cohorts. METHODS The study was a comparative analysis of Jewish respondents aged 75–94 from two nationwide random samples: the Cross-Sectional and Longitudinal Aging Study (1989–1992; N =1200) and the Survey of Health, Ageing, and Retirement in Europe (2005–2006; N =379). Self-reported functional limitation and disability were compared by means of logistic regressions and MANCOVA, controlling for age, gender, origin, education, marital status, income, self-rated health, and home care receipt. RESULTS Reported functional limitation decreased in the later cohort (SHARE-Israel), but ADL- and IADL-disability increased. Receipt of home care moderated these effects. ADL- and IADL-disability increased among home-care-receiving respondents in the later cohort whereas functional limitation decreased among respondents not in receipt of home care. DISCUSSION The findings suggest that different measures used to assess the disablement process capture different aspects, and that contextual factors influence how older people rate their own functional capacity. PMID:22422761

A Randomized, Clinical Trial of Preadmission Chlorhexidine Skin Preparation for Lower Extremity Total Joint Arthroplasty.

PubMed

Kapadia, Bhaveen H; Elmallah, Randa K; Mont, Michael A

2016-12-01

Periprosthetic infections are devastating postoperative complications of total joint arthroplasty (TJA), with native skin flora commonly identified as causative organisms. We compared 2% chlorhexidine gluconate-impregnated cloths to standard-of-care antiseptic bathing in patients before TJA, to evaluate periprosthetic infection risk at 1-year follow-up. This was a prospective, randomized, controlled trial at a single institution of patients undergoing hip or knee arthroplasty. Chlorhexidine-treated patients (275 arthroplasties) applied 2% chlorhexidine gluconate-impregnated cloths the night before and morning of admission. The standard-of-care cohort (279 arthroplasties) bathed with soap and water preadmission. Patients were excluded according to the following: (1) unable to comply with study requirements, (2) pregnant, (3) <18 years, (4) medical history of immunosuppression or steroid use, (5) chronic hepatitis B/C infection, (6) had infection around joint requiring surgery, or (7) chose not to participate. A total of 539 patients (554 arthroplasties) were included in the final population. There were no significant differences in American Society of Anesthesiologists grade, cut time, risk scores, or diabetes and smoking prevalence between cohorts (P > .05). A lower periprosthetic infection rate was found in the chlorhexidine cohort (0.4%) when compared to standard-of-care cohorts (2.9%). The infection odds ratio was 8.15 (95% confidence interval = 1.01-65.6; P = .049) for the standard-of-care cohort compared to the chlorhexidine cohort. No differences in assessed risk factors were found between groups. No severe adverse events were observed. Preoperative chlorhexidine cloth use decreased the risk of periprosthetic infection. This may be an appropriate antiseptic protocol to implement for patients undergoing lower extremity TJA. Copyright © 2016 Elsevier Inc. All rights reserved.

Change in social status and risk of low birth weight in Denmark: population based cohort study.

PubMed Central

Basso, O.; Olsen, J.; Johansen, A. M.; Christensen, K.

1997-01-01

OBJECTIVE: To estimate the risk of having a low birthweight infant associated with changes in social, environmental, and genetic factors. DESIGN: Population based, historical cohort study using the Danish medical birth registry and Statistic Denmark's fertility database. SUBJECTS: All women who had a low birthweight infant (< 2500 g) (index birth) and a subsequent liveborn infant (outcome birth) in Denmark between 1980 and 1992 (exposed cohort, n = 11,069) and a random sample of the population who gave birth to an infant weighing > or = 2500 g and to a subsequent liveborn infant (unexposed cohort, n = 10,211). MAIN OUTCOME MEASURES: Risk of having a low birthweight infant in the outcome birth as a function of changes in male partner, area of residence, type of job, and social status between the two births. RESULTS: Women in the exposed cohort showed a high risk (18.5%) of having a subsequent low birthweight infant while women in the unexposed cohort had a risk of 2.8%. After adjustment for initial social status, a decline in social status increased the absolute risk of having a low birthweight infant by about 5% in both cohorts, though this was significant only in the unexposed cohort. Change of male partner did not modify the risk of low birth weight in either cohort. CONCLUSION: Having had a low birthweight infant and a decline in social status are strong risk factors for having a low birthweight infant subsequently. PMID:9420490

Habitual coffee consumption and risk of cognitive decline/dementia: A systematic review and meta-analysis of prospective cohort studies.

PubMed

Liu, Qing-Ping; Wu, Yan-Feng; Cheng, Hong-Yu; Xia, Tao; Ding, Hong; Wang, Hui; Wang, Ze-Mu; Xu, Yun

2016-06-01

Findings from epidemiologic studies of coffee consumption and risk for cognitive decline or dementia are inconclusive. The aim of this study was to conduct a meta-analysis of prospective studies to assess the association between coffee consumption and the risk for cognitive decline and dementia. Relevant studies were identified by searching PubMed and Embase databases between 1966 and December 2014. Prospective cohorts that reported relative risk (RRs) and 95% confidence intervals (CIs) for the association of coffee consumption with dementia incidence or cognitive changing were eligible. Study-specific RRs were combined by using a random-effects model. Eleven prospective studies, including 29,155 participants, were included in the meta-analysis. The combined RR indicated that high coffee consumption was not associated with the different measures of cognitive decline or dementia (summary RR, 0.97; 95% CI, 0.84-1.11). Subgroup analyses suggested a significant inverse association between highest coffee consumption and the risk for Alzheimer disease (summary RR, 0.73; 95% CI, 0.55-0.97). The dose-response analysis, including eight studies, did not show an association between the increment of coffee intake and cognitive decline or dementia risk (an increment of 1 cup/d of coffee consumed; summary RR, 1.00; 95% CI, 0.98-1.02). The present study suggests that higher coffee consumption is associated with reduced risk for Alzheimer disease. Further randomized controlled trials or well-designed cohort studies are needed to determine the association between coffee consumption and cognitive decline or dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

Design innovations and baseline findings in a long-term Parkinson’s trial: NET-PD LS-1

PubMed Central

2012-01-01

Background Based on the pre-clinical and the results of a phase 2 futility study, creatine was selected for an efficacy trial in Parkinson’s disease (PD). We present the design rationale and a description of the study cohort at baseline. Methods A randomized, multicenter, double-blind, parallel group, placebo controlled Phase 3 study of creatine (10 gm daily) in participants with early, treated PD, the Long-term Study – 1 (LS-1) is being conducted by the NINDS Exploratory Trials in Parkinson’s Disease (NET-PD) network. The study utilizes a global statistical test (GST) encompassing multiple clinical rating scales to provide a multidimensional assessment of disease progression. Results A total of 1,741 PD participants from 45 sites in the U.S. and Canada were randomized 1:1 to either 10-gm creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. Conclusions LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. PMID:23079770

Topical Iodine And Fluoride Varnish Combined Is More Effective Than Fluoride Varnish Alone For Protecting Erupting First Permanent Molars: A Retrospective Cohort Study

PubMed Central

Tut, Ohnmar K.; Milgrom, Peter M.

2010-01-01

Objective This communication examines the combined effect of topical PVP-iodine plus fluoride varnish in prevention of tooth decay in erupting first permanent molars in an on-going public health program. Methods The evaluation employed a retrospective cohort design with two groups of children 60–83 months. Cohort 1 (2004–05) received three times per school year topical fluoride varnish, and Cohort 2 (2008–09) received topical application of 10% PVP-iodine followed at each visit with topical fluoride varnish. The children were examined clinically at the beginning and end of the school year. Results The proportion of children with caries-free first permanent molars in Cohort 2 (PVP-iodine plus fluoride varnish) was .883 and was greater than that in Cohort 1 (varnish), which was .785 (Chi-square=1.000E1, df 1, p<.002). Conclusions This evaluation of an on-going dental public health program adds evidence that topical antiseptics applied at the same time as fluoride varnish are more effective than varnish alone. Randomized trials are needed. PMID:20337902

Weight-Gain Reduction Among 2-Year College Students: The CHOICES RCT.

PubMed

Lytle, Leslie A; Laska, Melissa N; Linde, Jennifer A; Moe, Stacey G; Nanney, Marilyn S; Hannan, Peter J; Erickson, Darin J

2017-02-01

The young adult years have been recognized as an influential period for excess weight gain. Non-traditional students and those attending 2-year community colleges are at particularly high risk for a range of adverse weight-related outcomes. Choosing Healthy Options in College Environments and Settings was an RCT with students randomly assigned into a control or intervention condition after baseline assessment. The study was designed to evaluate if a 24-month weight-gain prevention intervention reduces the expected increase in BMI and overweight prevalence in young adults attending 2-year colleges. Two cohorts were recruited, corresponding to the fall and spring semesters. Data collection occurred at four time points for each cohort, with baseline occurring in fall 2011 for Cohort 1 and spring 2012 for Cohort 2. The 24-month follow-up occurred in fall 2013 for Cohort 1 and spring 2014 for Cohort 2. Data analysis occurred in 2015-2016. This research was conducted with 441 students from three community colleges in Minnesota. The 24-month intervention began with a 1-credit college course on healthy weight behaviors. A social networking and social support website was introduced as part of the course and participation encouraged for the duration of the trial. Changes in BMI, weight, body fat percentage, waist circumference, and weight status were assessed. Retention of the cohorts at 24 months was 83.4%. There was not a statistically significant difference in BMI between conditions at the end of the trial. However, there was a statically significant difference in the prevalence of overweight/obesity between treatment conditions at 24 months. Also, participants randomized to the intervention who were overweight or obese at baseline were more than three times as likely to transition to a healthy weight by the end of the trial as compared with control students. The intervention was not successful in achieving BMI differences between treatment groups. However, an 8% reduction in the prevalence of overweight and obesity over time may have population-level significance. This study is registered at www.clinicaltrials.gov NCT01134783. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Uranium and other natural radionuclides in drinking water and risk of leukemia: a case-cohort study in Finland.

PubMed

Auvinen, Anssi; Kurttio, Päivi; Pekkanen, Juha; Pukkala, Eero; Ilus, Taina; Salonen, Laina

2002-11-01

We assessed the effect of natural uranium and other radionuclides in drinking water on risk of leukemia. The subjects (n = 144,627) in the base cohort had lived outside the municipal tapwater system during 1967-1980. A subcohort was formed as a stratified random sample of the base cohort and subjects using drinking water from drilled wells prior to 1981 were identified. A case-cohort design was used comparing exposure among cases with leukemia (n = 35) with a stratified random sample (n = 274) from the subcohort. Activity concentrations of uranium, radium-226, and radon in the drinking water were analyzed using radiochemical and alpha-spectrometric methods. The median activity concentration of uranium in well water was 0.08 Bq/L for the leukemia cases and 0.06 Bq/L for the reference group, radon concentrations 80 and 130 Bq/L, respectively, and radium-226 concentrations 0.01 Bq/L for both groups. The hazard ratio of leukemia for uranium was 0.91 (95% confidence interval 0.73-1.13) per Bq/L. for radon 0.79 per Bq/L (95% CI 0.27-2.29), and for radium-226 0.80 (95% CI 0.46-1.39) per Bq/L. Our results do not indicate an increased risk of leukemia from ingestion of natural uranium or other radionuclides through drinking water at these exposure levels.

Validation of the pooled cohort risk score in an Asian population - a retrospective cohort study.

PubMed

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2014-11-20

The Pooled Cohort Risk Equation was introduced by the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 in their Blood Cholesterol Guideline to estimate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. However, absence of Asian ethnicity in the contemporary cohorts and limited studies to examine the use of the risk score limit the applicability of the equation in an Asian population. This study examines the validity of the pooled cohort risk score in a primary care setting and compares the cardiovascular risk using both the pooled cohort risk score and the Framingham General Cardiovascular Disease (CVD) risk score. This is a 10-year retrospective cohort study of randomly selected patients aged 40-79 years. Baseline demographic data, co-morbidities and cardiovascular (CV) risk parameters were captured from patient records in 1998. Pooled cohort risk score and Framingham General CVD risk score for each patient were computed. All ASCVD events (nonfatal myocardial infarction, coronary heart disease (CHD) death, fatal and nonfatal stroke) occurring from 1998-2007 were recorded. A total of 922 patients were studied. In 1998, mean age was 57.5 ± 8.8 years with 66.7% female. There were 47% diabetic patients and 59.9% patients receiving anti-hypertensive treatment. More than 98% of patients with pooled cohort risk score ≥7.5% had FRS >10%. A total of 45 CVD events occurred, 22 (7.2%) in males and 23 (3.7%) in females. The median pooled cohort risk score for the population was 10.1 (IQR 4.7-20.6) while the actual ASCVD events that occurred was 4.9% (45/922). Our study showed moderate discrimination with AUC of 0.63. There was good calibration with Hosmer-Lemeshow test χ2 = 12.6, P = 0.12. The pooled cohort risk score appears to overestimate CV risk but this apparent over-prediction could be a result of treatment. In the absence of a validated score in an untreated population, the pooled cohort risk score appears to be appropriate for use in a primary care setting.

Outcomes of Mini vs Roux-en-Y gastric bypass: A meta-analysis and systematic review.

PubMed

Wang, Fu-Gang; Yan, Wen-Mao; Yan, Ming; Song, Mao-Min

2018-05-10

Mini gastric bypass has been proved to be capable of achieving excellent metabolic results by numerous published studies. Compared to Roux-en-Y gastric bypass, mini gastric bypass is a technically simpler and reversible procedure. However, comparative outcomes of the effectiveness between Mini gastric bypass and Roux-en-Y gastric bypass remain unclear. A systematic literature search was performed in Pubmed, Embase, Cochrane library from inception to February 9, 2018. For assessment of method quality, NOS (Newcastle-Ottawa Scale) and Cochrane Collaboration's tool for assessing risk of bias were used for cohort study and randomized controlled trials, respectively. The meta-analysis was performed by RevMan 5.3 software. 10 cohort studies and 1 randomized controlled trial was included in our meta-analysis. The method quality of the 10 cohort studies was proved as high quality according to the Newcastle-Ottawa Scale. The randomized controlled trial was proved to have a low risk of bias according to Cochrane Collaboration's assessment. Patients receiving mini-gastric bypass had multiple advantageous indexes as compared with patients receiving Roux-en-Y gastric bypass. Examples include: a higher 1-year EWL% (P < 0.05), higher 2-year EWL% (P < 0.05), higher type 2 diabetes mellitus remission rate, as well as a shorter operation time (P < 0.05). No significant statistical difference was observed in hypertension remission rate, mortality, leakage rate, GERD rate, or hospital stay between mini gastric bypass and Roux-en-Y gastric bypass. Mini gastric bypass seems to be a simpler procedure with a better weight reduction effect. This seems to also be the case regarding remission rates of type 2 diabetes mellitus when using Mini gastric bypass in comparison to Roux-en-Y gastric bypass. A small sample size and biased data may have influenced the stability of our results. In light of this, surgeons should treat our results in a conservative way. Larger sample size and multi-center randomized control trials are needed to compare the effectiveness and safety between mini-gastric bypass and Roux-en-Y gastric bypass. Copyright © 2018. Published by Elsevier Ltd.

Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis.

PubMed

Truong, J; Lee, E K; Trudeau, M E; Chan, K K W

2016-04-01

Guidelines recommend primary prophylaxis (PP) with granulocyte-colony-stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. Practitioners often use FN rates of regimens based on data from randomized, controlled trials (RCTs), which are often comprised of highly selected patients. Patients in the community setting may be at higher risk of FN. A systematic literature search was conducted for full-length articles reporting FN rates for breast cancer-related chemotherapies between January 1996 and February 2014. A regimen was included if there was at least one RCT and one observational study. Meta-regression was used to model the odds of FN. 130 studies involving 29 regimens and 50 069 patients were identified. Sixty-five observational study (n = 7812) and 110 RCT (n = 42 257) cohorts were included. The unadjusted FN rate was 11.7% in observational and 7.9% in RCT cohorts. The univariable odds ratio (OR) for FN in the observational study compared with RCT cohorts was 1.58 [95% confidence interval (CI) 1.09-2.28; P = 0.017]. The FN rates remained significantly higher in the observational study compared with RCT cohorts (OR = 1.74; 95% CI 1.15-2.62; P = 0.012) after adjusting for age, chemotherapy intent, and regimen; this meant that a 13% (95% CI 8.7% to 17.9%) FN rate in RCT would translate into 20% FN rate in observational study. FN rates in the observational studies are significantly higher than suggested by RCTs. Guidelines should clarify how FN rates from RCTs should be applied in clinical practice. Large population-based studies are needed to confirm FN rates in the real world. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Variation in adherence to medications across the healthcare system in two comparative effectiveness research cohorts.

PubMed

Franklin, Jessica M; Donneyong, Macarius M; Desai, Rishi J; Markson, Leona; Girman, Cynthia J; McKay, Caroline; Patel, Mehul D; Mavros, Panagiotis; Schneeweiss, Sebastian

2017-10-01

To assess heterogeneity in adherence to medications in two example comparative effectiveness research studies. We analyzed data from commercially insured patients initiating a statin or anticoagulant during 2005-2012. We calculated the cross-validated R 2 from a series of hierarchical linear models to assess variation in 1-year adherence. There was less heterogeneity in adherence in the statin cohort compared with the anticoagulant cohort, where patient characteristics explained 7.2% of variation in adherence, and adding therapy and provider characteristics increased the proportion of variation explained to 8.0 and 8.5%, cumulatively. Random effects provided essentially no explanatory power, even in the statin cohort with large numbers of patients clustered within each pharmacy, prescriber and provider. The dependence of adherence on the healthcare system was stronger when the healthcare system influenced treatment choice and patient access to medication and when indications for treatment were strong.

Screening for asymptomatic bacteriuria in adults: evidence for the U.S. Preventive Services Task Force reaffirmation recommendation statement.

PubMed

Lin, Kenneth; Fajardo, Kevin

2008-07-01

Asymptomatic bacteriuria is common, and screening for this condition in pregnant women is a well-established, evidence-based standard of current medical practice. Screening other groups of adults has not been shown to improve outcomes. To review new and substantial evidence on screening for asymptomatic bacteriuria, to support the work of the U.S. Preventive Services Task Force. English-language studies of adults (age >18 years) indexed in PubMed and the Cochrane Library and published from 1 January 2002 through 30 April 2007. For benefits of screening or treatment for screened populations, systematic reviews; meta-analyses; and randomized, controlled trials were included. For harms of screening, systematic reviews; meta-analyses; randomized, controlled trials; cohort studies; case-control studies; and case series of large multisite databases were included. Two reviewers independently reviewed titles, abstracts, and full articles for inclusion. Two reviewers extracted data from studies on benefits of screening and treatment (including decreases in the incidence of adverse maternal and fetal outcomes, symptomatic urinary tract infections, hypertension, and renal function decline). An updated Cochrane systematic review of 14 randomized, controlled trials of treatment supports screening for asymptomatic bacteriuria in pregnant women. A randomized, controlled trial and a prospective cohort study show that screening nonpregnant women with diabetes for asymptomatic bacteriuria is unlikely to produce benefits. No new evidence on screening men for asymptomatic bacteriuria or on harms of screening was found. The focused search strategy may have missed some smaller studies on the benefits and harms of screening for asymptomatic bacteriuria. The available evidence continues to support screening for asymptomatic bacteriuria in pregnant women, but not in other groups of adults.

Should patients with asymptomatic significant carotid stenosis undergo simultaneous carotid and cardiac surgery?

PubMed Central

Ogutu, Peter; Werner, Raphael; Oertel, Frank; Beyer, Michael

2014-01-01

A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether patients with severe asymptomatic carotid and coronary artery diseases should undergo simultaneous carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). A total of 624 papers were found using the reported search, of which 20 represent the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study results of these papers are tabulated. Previous cohort studies showed mixed results, while advocating for the necessity of a randomized controlled trial (RCT). A recent RCT showed that patients undergoing prophylactic or simultaneous CEA + CABG had lower rates of stroke (0%) compared with delayed CEA 1–3 months after CABG (7.7%), without significant perioperative mortality difference. This study included patients with unilateral severe (>70%) asymptomatic carotid stenosis requiring CABG. An earlier partly randomized trial also showed better outcomes for patients undergoing simultaneous procedures (P = 0.045). Interestingly, systematic reviews previously failed to show compelling evidence supporting prophylactic CEA. This could be partly due to the fact that these reviews collectively analyse different cohort qualities. Neurological studies have, however, shown reduced cognitive and phonetic quality and function in patients with unilateral and bilateral asymptomatic carotid artery stenosis. Twenty-one RCTs comparing lone carotid artery stenting (CAS) and CEA informed the American Heart Association guidelines, which declared CAS comparable with CEA for symptomatic and asymptomatic carotid stenosis (CS). However, the risk of death/stroke for CAS alone is double that for CEA alone in the acute phase following onset of symptoms, while CEA alone is associated with a doubled risk of myocardial infarction. There is, however, no significant difference for combined 30-day risk of death/stroke/myocardial infarction. Outcomes of hybrid or simultaneous CAS/CABG procedures show comparable results, albeit from rather small cohorts. While current evidence leans towards simultaneous CEA/CABG, the emergence of hybrid operating theatres in various institutions may allow larger cohorts with subsequent significant data on simultaneous CAS/CABG. A randomized controlled trial comparing both approaches would be crucial in informing future updates of existing guidelines. PMID:24368551

Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

PubMed Central

Ruha, Anne-Michelle; Seifert, Steven A.; Morgan, David L.; Lewis, Brandon J.; Arnold, Thomas C.; Clark, Richard F.; Meggs, William J.; Toschlog, Eric A.; Borron, Stephen W.; Figge, Gary R.; Sollee, Dawn R.; Shirazi, Farshad M.; Wolk, Robert; de Chazal, Ives; Quan, Dan; García-Ubbelohde, Walter; Alagón, Alejandro; Gerkin, Richard D.; Boyer, Leslie V.

2015-01-01

Background. Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm3, fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. Results. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation. PMID:25361165

Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial.

PubMed

Bush, Sean P; Ruha, Anne-Michelle; Seifert, Steven A; Morgan, David L; Lewis, Brandon J; Arnold, Thomas C; Clark, Richard F; Meggs, William J; Toschlog, Eric A; Borron, Stephen W; Figge, Gary R; Sollee, Dawn R; Shirazi, Farshad M; Wolk, Robert; de Chazal, Ives; Quan, Dan; García-Ubbelohde, Walter; Alagón, Alejandro; Gerkin, Richard D; Boyer, Leslie V

2015-01-01

Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Do the Effects of Transcutaneous Electrical Nerve Stimulation on Knee Osteoarthritis Pain and Function Last?

PubMed

Cherian, Jeffrey Jai; Harrison, Paige E; Benjamin, Samantha A; Bhave, Anil; Harwin, Steven F; Mont, Michael A

2016-08-01

Transcutaneous electrical nerve stimulation (TENS) has been shown to decrease pain associated with knee osteoarthritis, which potentially leads to better function, improved quality of life, and postpones the need for surgical intervention. The purpose of this study was to perform a 1-year follow-up of a previous prospective group of patients with knee osteoarthritis, randomized to TENS or standard of care, who were asked to rate their changes in: (1) patient pain perception; (2) subjective medication use; (3) subjective functional abilities; (4) quality of life; (5) device use; and (6) conversion to TKA. A population of 70 patients were randomized to receive either a TENS device or a standard conservative therapy regimen. Patients were evaluated based on various subjective outcomes at minimum 1-year (mean, 19 months) follow-up. The TENS cohort had lower visual analog pain scores compared with the matching cohort. Subjective functional outcomes, as well as functional and activity scores, were also greater in the TENS cohort. Patients in TENS cohort showed significant improvements in their subjective and functional outcomes as compared with their initial status, while the control group did not show significant change. A majority of the TENS patients were able to reduce the amount of pain medications. Additionally, a large portion of the patients assigned to the TENS group continue to use the device, after completion of the trial. This study demonstrated the benefit of TENS for improving subjective outcomes in patients with pain due to knee osteoarthritis, compared with standard conservative treatments. The results of the study suggest that TENS is a safe and effective adjunct as part of the spectrum of current nonoperative treatment methods for knee osteoarthritis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Malignant transformation of oral submucous fibrosis in Taiwan: A nationwide population-based retrospective cohort study.

PubMed

Yang, Po-Yu; Chen, Yi-Tzu; Wang, Yu-Hsun; Su, Ni-Yu; Yu, Hui-Chieh; Chang, Yu-Chao

2017-11-01

Oral submucous fibrosis (OSF) is one of the well-recognized oral potentially malignant disorders. In this study, we investigated the malignant transformation of OSF in a Taiwanese population. A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort was randomly frequency-matched with the OSF cohort according to age, sex, and index year. Oral leukoplakia (OL) was further stratified to evaluate for the possible synergistic effects of OSF-associated malignant transformation. In this cohort, 71 (9.13%) of 778 cases of OSF were observed to transform into oral cancer. The malignant transformation rate was 29.26-fold in the OSF cohort than in the comparison cohort after adjustment (95% confidence intervals 20.55-41.67). To further stratify with OL, OSF with OL (52.46%; 95% confidence intervals 34.88-78.91) had higher risk of malignant transformation rate than OSF alone (29.84%; 95% confidence intervals 20.99-42.42). The Kaplan-Meier plot revealed the rate free of malignant transformation was significant over the 13-year follow-up period (log-rank test, P<.001). The mean duration of malignant transformation was 5.1, 2.7, and 2.2 years for non-OSF, OSF alone, and OSF with OL, respectively. Oral submucous fibrosis patients exhibited a significantly higher risk of malignant transformation than those without OSF. OL could enhance malignant transformation in patients with OSF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Substantia nigra depigmentation and exposure to encephalitis lethargica.

PubMed

Hack, Nawaz; Jicha, Gregory A; Abell, Annalisa; Dean, Dawson; Vitek, Jerrold L; Berger, Joseph R

2012-12-01

Parkinsonism has occasionally been reported as a consequence of infectious diseases. The present study examines the clinical and pathological correlates of parkinsonism across birth cohorts in relation to critical exposure to the encephalitis lethargica epidemic in the early 1900s. The study population consisted of 678 participants in the Nun Study, of whom 432 died and came to autopsy. Qualitative indices of substantia nigra (SN) depigmentation were verified in a subset of 40 randomly selected subjects using quantitative stereological techniques. SN depigmentation, detected neuropathologically, was correlated with clinical parameters of Parkinson disease, age, and birth cohort. SN depigmentation was detected in 57 (13.2%) of the cohort. Although qualitative SN depigmentation correlated modestly with age (p = 0.02), it correlated best with birth cohort (p = 0.009) for women born in the years 1895-1899. Quantitative measures of SN depigmentation were increased in this birth cohort compared to age matched subjects from flanking birth cohorts 1890-1894 and 1900-1904 (p < 0.001). SN depigmentation correlated with speed of 6- and 50-foot walk (p < 0.0001), up and go test (p < 0.0001), and hand coordination (p < 0.0001). Subjects in the birth cohort 1895-1899 would have been in their late teens and 20s at the onset and during the peak of the encephalitis lethargica epidemic. These were precisely the age ranges of persons who were most often affected by the illness. These data suggest the possibility that the coexistence of parkinsonism and SN depigmentation in this birth cohort may have resulted from the yet undetermined infectious agent responsible for encephalitis lethargica. Copyright © 2012 American Neurological Association.

A Classroom Observational Study of Qatar's Independent Schools: Instruction and School Reform

ERIC Educational Resources Information Center

Palmer, Douglas J.; Sadiq, Hissa M.; Lynch, Patricia; Parker, Dawn; Viruru, Radhika; Knight, Stephanie; Waxman, Hersh; Alford, Beverly; Brown, Danielle Bairrington; Rollins, Kayla; Stillisano, Jacqueline; Abu-Tineh, Abdullah M. Hamdan; Nasser, Ramzi; Allen, Nancy; Al-Binali, Hessa; Ellili, Maha; Al-Kateeb, Haithem; Al-Kubaisi, Huda

2016-01-01

Qatar initiated a K-12 national educational reform in 2001. However, there is limited information on the instructional practices of the teachers in the reform schools. This project was an observational study of classrooms with a stratified random sample of the first six cohorts of reform schools. Specifically, 156 classrooms were observed in 29…

Interventions to Reduce Distress in Adult Victims of Rape and Sexual Violence: A Systematic Review

ERIC Educational Resources Information Center

Regehr, Cheryl; Alaggia, Ramona; Dennis, Jane; Pitts, Annabel; Saini, Michael

2013-01-01

Objectives: This article presents a systematic evaluation of the effectiveness of interventions aimed at reducing distress in adult victims of rape and sexual violence. Method: Studies were eligible for the review if the assignment of study participants to experimental or control groups was by random allocation or parallel cohort design. Results:…

A systematic review on zinc for the prevention and treatment of age-related macular degeneration.

PubMed

Vishwanathan, Rohini; Chung, Mei; Johnson, Elizabeth J

2013-06-12

The objective of this systematic review was to examine the evidence on zinc intake from foods and supplements in the primary prevention and treatment of AMD. Randomized controlled trials (RCTs), prospective cohort, retrospective cohort, and case-control studies that investigated zinc intake from foods and/or supplements, and AMD in men and women with a mean age of 50 years or older were included. Medline and Cochrane Central were searched from inception to February 2012 and November 2012, respectively. Data extraction and quality appraisal were done on all eligible studies. TEN STUDIES WERE INCLUDED: four RCTs, four prospective cohort, and two retrospective cohort studies. Age-related Eye Disease Study (AREDS) showed zinc treatment to significantly reduce the risk of progression to advanced AMD. The risk of visual acuity loss was of similar magnitude, but not statistically significant. Two RCTs reported statistically significant increases in visual acuity in early AMD patients and one RCT showed no effect of zinc treatment on visual acuity in advanced AMD patients. Results from six cohort studies on associations between zinc intake and incidence of AMD were inconsistent. Current evidence on zinc intake for the prevention of AMD is inconclusive. Based on the strength of AREDS, we can conclude that zinc treatment may be effective in preventing progression to advanced AMD. Zinc supplementation alone may not be sufficient to produce clinically meaningful changes in visual acuity.

Observational studies are complementary to randomized controlled trials.

PubMed

Grootendorst, Diana C; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

2010-01-01

Randomized controlled trials (RCTs) are considered the gold standard study design to investigate the effect of health interventions, including treatment. However, in some situations, it may be unnecessary, inappropriate, impossible, or inadequate to perform an RCT. In these special situations, well-designed observational studies, including cohort and case-control studies, may provide an alternative to doing nothing in order to obtain estimates of treatment effect. It should be noted that such studies should be performed with caution and correctly. The aims of this review are (1) to explain why RCTs are considered the optimal study design to evaluate treatment effects, (2) to describe the situations in which an RCT is not possible and observational studies are an adequate alternative, and (3) to explain when randomization is not needed and can be approximated in observational studies. Examples from the nephrology literature are used for illustration. Copyright 2009 S. Karger AG, Basel.

Retention of Statistical Concepts in a Preliminary Randomization-Based Introductory Statistics Curriculum

ERIC Educational Resources Information Center

Tintle, Nathan; Topliff, Kylie; VanderStoep, Jill; Holmes, Vicki-Lynn; Swanson, Todd

2012-01-01

Previous research suggests that a randomization-based introductory statistics course may improve student learning compared to the consensus curriculum. However, it is unclear whether these gains are retained by students post-course. We compared the conceptual understanding of a cohort of students who took a randomization-based curriculum (n = 76)…

Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study.

PubMed

Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Sung, Fung-Chang; Kao, Chia-Hung

2015-10-01

The association between enterovirus infections in children and risk of leukaemia is unclear. We aimed to assess the risk of leukaemia after enterovirus infection in children. We did a nationwide retrospective cohort study by analysing data from the National Health Insurance Research Database (NHIRD) in Taiwan. Children with enterovirus infections aged younger than 18 years were identified. With use of computer-generated random numbers, children not infected with enterovirus were randomly selected and frequency matched (1:1) with children infected with enterovirus by sex, age, urbanisation level, parental occupation, and index year of enterovirus infection. We only included children with complete baseline data for age and sex and who had at least three clinic visits with the diagnosis of enterovirus infection. The diagnosis date of the first clinic visit for the enterovirus infection was defined as the index date for initiation of follow-up person-year measurement and participants. All study patients were followed up until they developed leukaemia, were lost to follow-up, withdrew from the NHI programme, or until the end of the study without leukaemia (censored). Our primary endpoint was a diagnosis of leukaemia during follow-up. Insurance claims data for 3 054 336 children younger than 18 years were randomly selected from all insured children in the NHIRD. We identified 282 360 children infected with enterovirus and 282 355 children not infected with enterovirus between Jan 1, 2000, and Dec 31, 2007. The incidence density rates of leukaemia were 3·26 per 100 000 person-years for the enterovirus-infected and 5·84 per 100 000 person-years for the non-enterovirus-infected cohorts. The risk of leukaemia was significantly lower in the enterovirus-infected cohort than in the non-enterovirus-infected cohort (adjusted subhazard ratio [SHR] 0·44, 95% CI 0·31-0·60; p<0·0001). Children infected with enterovirus have a reduced risk of both lymphocytic leukaemia (adjusted SHR 0·44, 0·30-0·65; p<0·0001) and acute myeloid leukaemia (adjusted SHR 0·40, 0·17-0·97; p=0·04). Herpangina and hand-foot-and-mouth disease were the main diseases associated with the reduced risk of leukaemia. The association between enterovirus infection and the reduced risk of developing leukaemia supports Greaves' delayed infection hypothesis for the cause of childhood leukaemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Alcoholic Intoxication on the Risk of Inflammatory Bowel Disease: A Nationwide Retrospective Cohort Study

PubMed Central

Hsu, Tai-Yi; Shih, Hong-Mo; Wang, Yu-Chiao; Lin, Leng-Chieh; He, Guan-Yi; Chen, Chih-Yu; Kao, Chia-Hung; Chen, Chao-Hsien

2016-01-01

Purpose This study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan. Methods This retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI. Results The incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19–4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001). Conclusion The risk of IBD was higher in patients with AI and increased with the length of hospital stay. PMID:27802288

Association of Traditional Chinese Medicine Therapy and the Risk of Vascular Complications in Patients With Type II Diabetes Mellitus: A Nationwide, Retrospective, Taiwanese-Registry, Cohort Study.

PubMed

Lee, Ai-Lin; Chen, Bor-Chyuan; Mou, Chih-Hsin; Sun, Mao-Feng; Yen, Hung-Rong

2016-01-01

With an increasing use of traditional Chinese medicine (TCM) in type 2 diabetes mellitus (T2DM), evidence of long-term benefit with adjunctive TCM treatment is limited. This study investigated whether the concurrent TCM treatment reduces the risk of vascular complications in T2DM patients by using a large population from National Health Insurance Research Database (NHIRD).We identified 33,457 adult patients with newly diagnosed T2DM using anti-diabetic agents from a random sample of one million beneficiaries in the NHIRD between January 1, 2000 and December 31, 2011. We recruited 1049 TCM users (received TCM over 30 days with a diagnosis of T2DM) and randomly selected 4092 controls as the non-TCM cohort at a ratio of 1:4 frequency-matched by age, sex, hypertension, hyperlipidemia, and index year. We investigated the prescription pattern of TCM and conducted a Cox proportional hazards regression to calculate the hazard ratios (HRs) of stroke, chronic kidney diseases (CKD), and diabetic foot between the 2 cohorts.In the TCM cohort, the prescription pattern of TCM was different between insulin and noninsulin patients. The most common herbs were Dan-Shen (Radix Salviae Miltiorrhizae) in noninsulin group and Da-Huang (Radix et Rhizoma Rhei) in insulin group. The most common formulae were Liu-Wei-Di-Huang-Wan in noninsulin group and Yu-Quan-Wan in insulin group. Although no significant reduction in the hazard ratio of CKD and diabetic foot, the incidence rate of stroke was 7.19 per 1000 person-years in the TCM cohort and 10.66 per 1000 person-years in the control cohort, respectively. After adjustment of age, sex, hypertension, hyperlipidemia, and antidiabetes agent use (including sulfonylureas, α-glucosidase, metformin, meglitinide, thiazolidinediones, and insulin), TCM cohorts were found to have a 33% decreased risk of stroke (95% CI = 0.46-0.97; P < 0.05).This population-based retrospective study showed that the complementary TCM therapy might associate with the decreased risk of stroke in T2DM, suggesting TCM as an adjunctive therapy for T2DM to prevent subsequent stroke.

Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and meta-analysis.

PubMed

Cintron, Dahima; Rodriguez-Gutierrez, Rene; Serrano, Valentina; Latortue-Albino, Paula; Erwin, Patricia J; Murad, Mohammad Hassan

2017-02-01

Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twenty-five studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04-0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82-13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.

The Porto Alegre Early Life Nutrition and Health Study.

PubMed

Chaffee, Benjamin Wilk; Vítolo, Márcia Regina; Feldens, Carlos Alberto

2014-12-01

Early childhood caries is a persistent worldwide problem. The etiologic contribution of feeding practices has been less frequently investigated in prospective studies of young children. The Porto Alegre Early Life Nutrition and Health Study has followed a birth cohort of 715 mother-child pairs, recruited from municipal health centers, originally involved in a cluster-randomized controlled trial of healthcare worker training. The birth cohort links prospectively collected socio-demographic, infant feeding, and general and oral health information. To date, oral health data, including caries status and oral health-related quality of life, have been collected for 458 children at the age of 2-3 years. Studies are underway to investigate possible determinants and consequences of oral health among these children.

Electronic Health Records and Information Portability: A Pilot Study in a Rural Primary Healthcare Center in India

PubMed Central

Radhakrishna, Kedar; Goud, B. Ramakrishna; Kasthuri, Arvind; Waghmare, Abijeet; Raj, Tony

2014-01-01

Clinical documentation and health information portability pose unique challenges in urban and rural areas of India. This article presents findings of a pilot study conducted in a primary health center in rural India. In this article, we focus on primary care in rural India and how a portable health record system could facilitate the availability of medical information at the point of care. We followed a geriatric cohort and a maternal cohort of 308 participants over a nine-month period. Physician encounters were entered into a web-based electronic health record. This information was made available to all study participants through a short messaging service (SMS). Additionally, 135 randomly selected participants from the cohort were issued a USB-based memory card that contained their detailed health records and could be viewed on most computers. The dual portability model implemented in the pilot study demonstrates the utility of the concept. PMID:25214819

Shift work, night work, and the risk of prostate cancer: A meta-analysis based on 9 cohort studies.

PubMed

Du, Hong-Bing; Bin, Kai-Yun; Liu, Wen-Hong; Yang, Feng-Sheng

2017-11-01

Epidemiology studies suggested that shift work or night work may be linked to prostate cancer (PCa); the relationship, however, remains controversy. PubMed, ScienceDirect, and Embase (Ovid) databases were searched before (started from the building of the databases) February 4, 2017 for eligible cohort studies. We pooled the evidence included by a random- or fixed-effect model, according to the heterogeneity. A predefined subgroup analysis was conducted to see the potential discrepancy between groups. Sensitivity analysis was used to test whether our results were stale. Nine cohort studies were eligible for meta-analysis with 2,570,790 male subjects. Our meta-analysis showed that, under the fixed-effect model, the pooled relevant risk (RR) of PCa was 1.05 (95% confidence interval [CI]: 1.00, 1.11; P = .06; I = 24.00%) for men who had ever engaged in night shift work; and under the random-effect model, the pooled RR was 1.08 (0.99, 1.17; P = .08; I = 24.00%). Subgroup analysis showed the RR of PCa among males in western countries was 1.05 (95% CI: 0.99, 1.11; P = .09; I = 0.00%), while among Asian countries it was 2.45 (95% CI: 1.19, 5.04; P = .02; I = 0.00%); and the RR was 1.04 (95% CI: 0.95, 1.14; P = .40; I = 29.20%) for the high-quality group compared with 1.21 (95% CI: 1.03, 1.41; P = .02; I = 0.00%) for the moderate/low-quality group. Sensitivity analysis showed robust results. Based on the current evidence of cohort studies, we found no obvious association between night shift work and PCa. However, our subgroup analysis suggests that night shift work may increase the risk of PCa in Asian men. Some evidence of a small study effect was observed in this meta-analysis.

The effect of two lottery-style incentives on response rates to postal questionnaires in a prospective cohort study in preschool children at high risk of asthma: a randomized trial.

PubMed

van der Mark, Lonneke B; van Wonderen, Karina E; Mohrs, Jacob; Bindels, Patrick Je; Puhan, Milo A; Ter Riet, Gerben

2012-12-18

In research with long-term follow-up and repeated measurements, quick and complete response to questionnaires helps ensure a study's validity, precision and efficiency. Evidence on the effect of non-monetary incentives on response rates in observational longitudinal research is scarce. To study the impact of two strategies to enhance completeness and efficiency in observational cohort studies with follow-up durations of around 2 years. METHOD AND INTERVENTION: In a factorial design, 771 children between 2 and 5 years old and their parents participating in a prospective cohort study were randomized to three intervention groups and a control group. Three types of lotteries were run: (i) daytrip tickets for the whole family to a popular amusement park if they returned all postal questionnaires, (ii) €12.50-worth gift vouchers for sending back the questionnaire on time after each questionnaire round and (iii) a combination of (i) and (ii). Primary outcome was the proportion of participants who returned all questionnaires without any reminder. Secondary outcomes were '100% returned with or without reminder', 'probability of 100% non-response', 'probability of withdrawal', 'proportion of returned questionnaires' and 'overall number of reminders sent'. After testing for interaction between the two lottery interventions, the two trials were analysed separately. We calculated risk differences (RD) and numbers needed to "treat" and their 95% confidence intervals. Daytrip nor voucher intervention had an effect on the proportion of participants who returned all questionnaires (RD -0.01; 95% CI-0.07 - 0.06) and (RD 0.02; 95% CI-0.50 - 0.08), respectively. No effects were found on the secondary outcomes. Our findings do not support the idea that lottery-style incentives lead to more complete response to postal questionnaires in observational cohort studies with repeated data collection and follow-up durations of around 2 years.

Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

PubMed

Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

2017-03-28

Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1.

PubMed

Elm, Jordan J

2012-10-01

Based on the preclinical data and the results of a phase II futility study, creatine was selected for an efficacy trial in Parkinson's disease (PD). We present the design rationale and a description of the study cohort at baseline. A randomized, multicenter, double-blind, parallel-group, placebo-controlled phase III study of creatine (10 g daily) in participants with early, treated PD, the Long-term Study-1 (LS-1), is being conducted by the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease network. The study utilizes a global statistical test (GST) encompassing five clinical rating scales to provide a multidimensional assessment of disease progression. A total of 1,741 PD participants from 45 sites in the United States and Canada were randomized 1:1 to either 10 g of creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10 g/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5-year follow-up visit against the background of dopaminergic therapy and best PD care. Copyright © 2012 Movement Disorder Society.

Across-cohort QC analyses of GWAS summary statistics from complex traits.

PubMed

Chen, Guo-Bo; Lee, Sang Hong; Robinson, Matthew R; Trzaskowski, Maciej; Zhu, Zhi-Xiang; Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Kutalik, Zoltán; Loos, Ruth J F; Frayling, Timothy M; Hirschhorn, Joel N; Yang, Jian; Wray, Naomi R; Visscher, Peter M

2016-01-01

Genome-wide association studies (GWASs) have been successful in discovering SNP trait associations for many quantitative traits and common diseases. Typically, the effect sizes of SNP alleles are very small and this requires large genome-wide association meta-analyses (GWAMAs) to maximize statistical power. A trend towards ever-larger GWAMA is likely to continue, yet dealing with summary statistics from hundreds of cohorts increases logistical and quality control problems, including unknown sample overlap, and these can lead to both false positive and false negative findings. In this study, we propose four metrics and visualization tools for GWAMA, using summary statistics from cohort-level GWASs. We propose methods to examine the concordance between demographic information, and summary statistics and methods to investigate sample overlap. (I) We use the population genetics F st statistic to verify the genetic origin of each cohort and their geographic location, and demonstrate using GWAMA data from the GIANT Consortium that geographic locations of cohorts can be recovered and outlier cohorts can be detected. (II) We conduct principal component analysis based on reported allele frequencies, and are able to recover the ancestral information for each cohort. (III) We propose a new statistic that uses the reported allelic effect sizes and their standard errors to identify significant sample overlap or heterogeneity between pairs of cohorts. (IV) To quantify unknown sample overlap across all pairs of cohorts, we propose a method that uses randomly generated genetic predictors that does not require the sharing of individual-level genotype data and does not breach individual privacy.

Across-cohort QC analyses of GWAS summary statistics from complex traits

PubMed Central

Chen, Guo-Bo; Lee, Sang Hong; Robinson, Matthew R; Trzaskowski, Maciej; Zhu, Zhi-Xiang; Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Kutalik, Zoltán; Loos, Ruth J F; Frayling, Timothy M; Hirschhorn, Joel N; Yang, Jian; Wray, Naomi R; Visscher, Peter M

2017-01-01

Genome-wide association studies (GWASs) have been successful in discovering SNP trait associations for many quantitative traits and common diseases. Typically, the effect sizes of SNP alleles are very small and this requires large genome-wide association meta-analyses (GWAMAs) to maximize statistical power. A trend towards ever-larger GWAMA is likely to continue, yet dealing with summary statistics from hundreds of cohorts increases logistical and quality control problems, including unknown sample overlap, and these can lead to both false positive and false negative findings. In this study, we propose four metrics and visualization tools for GWAMA, using summary statistics from cohort-level GWASs. We propose methods to examine the concordance between demographic information, and summary statistics and methods to investigate sample overlap. (I) We use the population genetics Fst statistic to verify the genetic origin of each cohort and their geographic location, and demonstrate using GWAMA data from the GIANT Consortium that geographic locations of cohorts can be recovered and outlier cohorts can be detected. (II) We conduct principal component analysis based on reported allele frequencies, and are able to recover the ancestral information for each cohort. (III) We propose a new statistic that uses the reported allelic effect sizes and their standard errors to identify significant sample overlap or heterogeneity between pairs of cohorts. (IV) To quantify unknown sample overlap across all pairs of cohorts, we propose a method that uses randomly generated genetic predictors that does not require the sharing of individual-level genotype data and does not breach individual privacy. PMID:27552965

Risk of thyroid cancer in patients with thyroiditis: a population-based cohort study.

PubMed

Liu, Chien-Liang; Cheng, Shih-Ping; Lin, Hui-Wen; Lai, Yuen-Liang

2014-03-01

The causative relationship between autoimmune thyroiditis and thyroid cancer remains a controversial issue. The aim of this population-based study was to investigate the risk of thyroid cancer in patients with thyroiditis. From the Longitudinal Health Insurance Database 2005 (LHID2005) of Taiwan, we identified adult patients newly diagnosed with thyroiditis between 2004 and 2009 (n = 1,654). The comparison cohort (n = 8,270) included five randomly selected age- and sex-matched controls for each patient in the study cohort. All patients were followed up from the date of cohort entry until they developed thyroid cancer or to the end of 2010. Multivariate Cox regression was used to assess the risk of developing thyroid cancer. A total of 1,000 bootstrap replicates were created for internal validation. A total of 35 patients developed thyroid cancer during the study period, of whom 24 were from the thyroiditis cohort and 11 were from the comparison cohort (incidence 353 and 22 per 100,000 person-years, respectively). After adjusting for potential confounding factors, the hazard ratio (HR) for thyroid cancer in patients with thyroiditis was 13.24 (95 % CI 6.40-27.39). Excluding cancers occurring within 1 year of follow-up, the HR remained significantly increased (6.64; 95 % CI 2.35-18.75). Hypothyroidism was not an independent factor associated with the occurrence of thyroid cancer. We found an increased risk for the development of thyroid cancer after a diagnosis of thyroiditis, independent of comorbidities.

Primary Sjogren's syndrome and the risk of acute pancreatitis: a nationwide cohort study.

PubMed

Chang, Chi-Ching; Chang, Yu-Sheng; Wang, Shu-Hung; Lin, Shyr-Yi; Chen, Yi-Hsuan; Chen, Jin Hua

2017-08-11

Studies on the risk of acute pancreatitis in patients with primary Sjogren's syndrome (pSS) are limited. We evaluated the effects of pSS on the risk of acute pancreatitis in a nationwide, population-based cohort in Taiwan. Population-based retrospective cohort study. We studied the claims data of the >97% Taiwan population from 2002 to 2012. We identified 9468 patients with pSS by using the catastrophic illness registry of the National Health Insurance Database in Taiwan. We also selected 37 872 controls that were randomly frequency matched by age (in 5 year bands), sex and index year from the general population. We analysed the risk of acute pancreatitis by using Cox proportional hazards regression models including sex, age and comorbidities. From 23.74 million people in the cohort, 9468 patients with pSS (87% women, mean age=55.6 years) and 37 872 controls were followed-up for 4.64 and 4.74 years, respectively. A total of 44 cases of acute pancreatitis were identified in the pSS cohort versus 105 cases in the non-pSS cohort. Multivariate Cox regression analysis indicated that the incidence rate of acute pancreatitis was significantly higher in the pSS cohort than in the non-pSS cohort (adjusted HR (aHR) 1.48, 95% CI 1.03 to 2.12). Cyclophosphamide use increased the risk of acute pancreatitis (aHR 5.27, 95% CI 1.16 to 23.86). By contrast, hydroxychloroquine reduced the risk of acute pancreatitis (aHR 0.23, 95% CI 0.09 to 0.55). This nationwide, retrospective cohort study demonstrated that the risk of acute pancreatitis was significantly higher in patients with pSS than in the general population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Plasma and Dietary Antioxidant Status as Cardiovascular Disease Risk Factors: A Review of Human Studies

PubMed Central

Wang, Ying; Chun, Ock K.; Song, Won O.

2013-01-01

Extensive evidence has demonstrated that many antioxidants such as vitamin C, vitamin E, carotenoids and polyphenols have protective effects in preventing cardiovascular disease (CVD), a chronic disease that is mediated by oxidative stress and inflammation. This review focuses on evidence from prospective cohort studies and clinical trials in regard to the associations between plasma/dietary antioxidants and cardiovascular events. Long-term, large-scale, population-based cohort studies have found that higher levels of serum albumin, bilirubin, glutathione, vitamin E, vitamin C, and carotenoids were associated with a lower risk of CVD. Evidence from the cohort studies in regard to dietary antioxidants also supported the protective effects of dietary vitamin E, vitamin C, carotenoids, and polyphenols on CVD risk. However, results from large randomized controlled trials did not support long-term use of single antioxidant supplements for CVD prevention due to their null or even adverse effects on major cardiovascular events or cancer. Diet quality indexes that consider overall diet quality rather than single nutrients have been drawing increasing attention. Cohort studies and intervention studies that focused on diet patterns such as high total antioxidant capacity have documented protective effects on CVD risk. This review provides a perspective for future studies that investigate antioxidant intake and risk of CVD. PMID:23912327

The incident user design in comparative effectiveness research.

PubMed

Johnson, Eric S; Bartman, Barbara A; Briesacher, Becky A; Fleming, Neil S; Gerhard, Tobias; Kornegay, Cynthia J; Nourjah, Parivash; Sauer, Brian; Schumock, Glen T; Sedrakyan, Art; Stürmer, Til; West, Suzanne L; Schneeweiss, Sebastian

2013-01-01

Comparative effectiveness research includes cohort studies and registries of interventions. When investigators design such studies, how important is it to follow patients from the day they initiated treatment with the study interventions? Our article considers this question and related issues to start a dialogue on the value of the incident user design in comparative effectiveness research. By incident user design, we mean a study that sets the cohort's inception date according to patients' new use of an intervention. In contrast, most epidemiologic studies enroll patients who were currently or recently using an intervention when follow-up began. We take the incident user design as a reasonable default strategy because it reduces biases that can impact non-randomized studies, especially when investigators use healthcare databases. We review case studies where investigators have explored the consequences of designing a cohort study by restricting to incident users, but most of the discussion has been informed by expert opinion, not by systematic evidence. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Dinitrotoluene exposure in the copper mining industry and renal cancer: a case-cohort study.

PubMed

Seidler, Andreas; Harth, Volker; Taeger, Dirk; Möhner, Matthias; Gawrych, Katarzyna; Bergmann, Annekatrin; Haerting, Johannes; Kahmann, Hans-Joachim; Bolt, Hermann Maximilian; Straif, Kurt; Brüning, Thomas

2014-04-01

To evaluate the association between dinitrotoluene (DNT) exposure and renal cancer in a case-cohort study. This case-cohort study was conducted among men born between 1920 and 1974 (n=16 441) who were gainfully employed between 1953 and 1990 in one of two copper mines in Mansfeld, Saxony-Anhalt, former German Democratic Republic, and followed up till 31 December 2006. The study included 109 cases with renal cancer identified by record linkage with the Common Cancer Registry of the New Federal States of Germany (GKR) or by a network of pathology institutes. A comparison subcohort of 999 cohort members was selected at random from the total cohort. Duration and intensity of inhalation and dermal exposure to DNT were assessed on the basis of a job exposure matrix. A time-dependent Cox proportional hazards model modified for case-cohort design was used to assess the relationship between cumulative inhalation and dermal DNT exposure and renal cancer. Elevated risks were found for medium (HR=2.73; 95% CI 1.00 to 7.42) and high (HR=1.81; 95% CI 0.75 to 4.33) dermal exposure to DNT. Relative risks for medium inhalation exposure to DNT were not increased (HR=0.93; 95% CI 0.48 to 1.79) while relative risks for high inhalation exposure to DNT were elevated to 1.36 (95% CI 0.84 to 2.21). We found a statistically significant HR of 2.12 (95% CI 1.03 to 4.37) for combined medium or high inhalation and medium or high dermal exposure to DNT. According to our case-cohort study, dermal and inhalation exposure to DNT is associated with increased renal cancer risk.

Setting up a Cohort Study in Speech and Language Therapy: Lessons from the UK Cleft Collective Speech and Language (CC-SL) Study

ERIC Educational Resources Information Center

Wren, Yvonne; Humphries, Kerry; Stock, Nicola Marie; Rumsey, Nichola; Lewis, Sarah; Davies, Amy; Bennett, Rhiannon; Sandy, Jonathan

2018-01-01

Background: Efforts to increase the evidence base in speech and language therapy are often limited by methodological factors that have restricted the strength of the evidence to the lower levels of the evidence hierarchy. Where higher graded studies, such as randomized controlled trials, have been carried out, it has sometimes been difficult to…

The association between the combined oral contraceptive pill and insulin resistance, dysglycemia and dyslipidemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of observational studies.

PubMed

Halperin, Ilana J; Kumar, Shoba Sujana; Stroup, Donna F; Laredo, Sheila E

2011-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of young women. First-line treatment is often the oral contraceptive pill (OC), but evidence suggests that OC may worsen metabolic outcomes in this population. We undertook this meta-analysis of observational studies and cohorts from within randomized controlled studies to investigate the association between OC use and dysglycemia, dyslipidemia and insulin resistance (IR) in women with PCOS. We searched MEDLINE (1966-April 2010), EMBASE (1980-April 2010) and All EBM Reviews. We included prospective cohorts and RCTs that treated women, aged 13-44, with PCOS with OC for at least 3 months. Blinded quality assessment and data extraction were conducted on 35 included studies by two independent reviewers. We used random effects methods to calculate weighted mean differences as the effect size. We investigated heterogeneity using sequential removal of studies, subgroup analysis and meta-regression. OC use was significantly associated with an increase in high-density lipoprotein cholesterol (HDL-C) (P = 0.004) and triglycerides (P = 0.004). Significant heterogeneity was found in glucose, cholesterol, HDL-C, low-density lipoprotein cholesterol triglycerides, fasting glucose to insulin ratios and homeostatic model assessments-IR. Study characteristics such as mean BMI, mean age and duration of study could explain some of the heterogeneity. Use of OC was not associated with clinically significant adverse metabolic consequences. Because of limitations of the underlying studies, further research including rigorously designed randomized trials would more definitively confirm our findings.

A systematic review of the association between consumption of sugar-containing beverages and excess weight gain among children under age 12.

PubMed

Frantsve-Hawley, Julie; Bader, James D; Welsh, Jean A; Wright, J Timothy

2017-06-01

A systematic review was conducted to address this clinical question: Does consumption of (non-dairy) sugar-containing beverages (SCBs) among children under age 12 result in excess weight gain? The authors searched four databases for controlled trials (randomized and non-randomized) and cohort studies published in English through March 29, 2016: PubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL. Initial and full-text screening, data abstraction, and risk of bias assessment were performed independently and in duplicate. Thirty-eight studies met inclusion criteria for this systematic review. One was a randomized controlled trial, and 37 were cohort studies. Though the results of these studies were mixed, the majority demonstrated a statistically significant positive association between SCB consumption in children under age 12 and total adiposity and central adiposity. In contrast, most studies that assessed 100 percent fruit juice consumption only with either total adiposity or central adiposity did not support an association. Among only children under age 5 at baseline, no studies examined central adiposity, but nearly all studies examining SCBs and total adiposity, and a majority examining only fruit juice consumption, demonstrated a statistically significant positive association. Our results support a statistically significant positive association between SCBs and total and central adiposity among children under age 12. This association is most consistent for total adiposity among children <5. Our results for 100 percent fruit juice only suggest differences by age, as most studies among those < 12 were negative but most among those <5 were positive. © 2017 American Association of Public Health Dentistry.

SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

PubMed

Swoboda, Kathryn J; Scott, Charles B; Crawford, Thomas O; Simard, Louise R; Reyna, Sandra P; Krosschell, Kristin J; Acsadi, Gyula; Elsheik, Bakri; Schroth, Mary K; D'Anjou, Guy; LaSalle, Bernard; Prior, Thomas W; Sorenson, Susan L; Maczulski, Jo Anne; Bromberg, Mark B; Chan, Gary M; Kissel, John T

2010-08-19

Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo. Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures. At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007). This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials. Clinicaltrials.gov NCT00227266.

A Comparison Study of the Effectiveness of the Lexia Reading Programme

ERIC Educational Resources Information Center

Ness, Mike; Couperus, Josh; Willey, Matthew

2013-01-01

This study evaluates the efficacy of the Lexia Reading (LR) programme with a cohort of 37 students in a Decile 1 primary school. The students were randomly assigned to experimental (who used LR) and control groups (who did not use LR). The WIAT-II was used to provide pre and post measures of literacy skills. Results indicated that students who…

What Works Clearinghouse Quick Review of the Report "Reading and Language Outcomes of a Five-Year Randomized Evaluation of Transitional Bilingual Education"

ERIC Educational Resources Information Center

What Works Clearinghouse, 2010

2010-01-01

The study examined how the English reading performance of predominantly Spanish-speaking students in transitional bilingual education compared with the performance of predominantly Spanish-speaking students in structured English immersion. The study analyzed data on three cohorts of students in six schools in Los Angeles; Denver; Albuquerque; St.…

Social adjustment and competence 35 years after onset of childhood epilepsy: a prospective controlled study.

PubMed

Jalava, M; Sillanpää, M; Camfield, C; Camfield, P

1997-06-01

To study the effect of childhood-onset epilepsy without other neurologic deficit on adult social adjustment and competence. Social competence was studied in a prospective, population-based cohort of childhood-onset epilepsy after a mean follow-up of 35 years. One hundred patients (60% of the total cohort) had no other neurologic problems ("epilepsy only"), and for each patient, two matched controls, a "random" control and an "employee" control were chosen. Good social outcome was significantly reduced in the "epilepsy only" cohort compared with random controls: education [cumulative odds ratio (COR), 2.4; 95% confidence interval (CI), 1.4-4.1]; employability (COR, 7.3; 95% CI, 2.7-20.0); and marriage rate (COR, 3.7; 95% CI, 1.9-7.3). The patients with epilepsy rated their own ability to control their lives as "poor or missing" four times more frequently than the employee controls. Patients receiving antiepileptic polytherapy, but not monotherapy, were significantly less satisfied with their present life (OR, 6.7; 95% CI, 1.9-24.1) and felt their general health was significantly poorer (OR, 5.1; 95% CI, 1.2-21.3) than did the employee controls. Furthermore, patients with continuing seizures were significantly less satisfied with their present life (OR, 4.1; 95% CI, 1.1-15.1) than were employee controls. Many patients with "epilepsy only" beginning in childhood have persistent and significant social-adjustment and competence problems in adulthood.

Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study

PubMed Central

Ganna, Andrea; Brandmaier, Stefan; Broeckling, Corey D.; Prenni, Jessica E.; Wang-Sattler, Rui; Peters, Annette; Strauch, Konstantin; Meitinger, Thomas; Giedraitis, Vilmantas; Ärnlöv, Johan; Berne, Christian; Gieger, Christian; Ripatti, Samuli; Lind, Lars; Sundström, Johan; Ingelsson, Erik

2016-01-01

Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining “gold standard” measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development. PMID:27768686

Chronic Use of Theophylline and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-analysis.

PubMed

Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

2016-05-01

Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated. Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I(2)<50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio. We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I(2)=42%, P=.11) and publication bias (Begg's test r=0.21, P=.662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P=.003). This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

The Inconvenience of Convenience Cohorts: Rhabdomyosarcoma and the PAX-FOXO1 Biomarker

PubMed Central

Rosenberg, Abby R.; Skapek, Stephen X.; Hawkins, Douglas S.

2012-01-01

“Convenience cohorts” comprise individuals thought to represent the general population, but chosen because they are readily available for evaluation, rather than at random. As such, these methods are subject to bias and may be misleading. Convenience cohorts have been used to investigate the prognostic significance of chromosomal translocations between the PAX3 or PAX7 and the FOXO1 genes in rhabdomyosarcoma, the most common pediatric sarcoma. However, retrospective studies assessing the role of PAX-FOXO1 translocations have yielded inconsistent results. This review highlights the findings from several clinical correlation studies of the PAX-FOXO1 biomarker and illustrates the challenges of using such methods to draw clinical conclusions. PMID:22564868

Hypnosis versus diazepam for embryo transfer: a randomized controlled study.

PubMed

Catoire, Patrick; Delaunay, Laurent; Dannappel, Thomas; Baracchini, Dominique; Marcadet-Fredet, Sabine; Moreau, Olivier; Pacaud, Luc; Przyrowski, Daniel; Marret, Emmanuel

2013-04-01

Levitas et al. (2006) showed in a cohort study that hypnosis during embryo transfer (ET) increased pregnancy ratio by 76%. In order to evaluate hypnosis during ET in a general population, the authors performed a randomized prospective controlled study comparing diazepam (usual premedication) administered before ET plus muscle relaxation versus hypnosis plus placebo in 94 patients. Additionally, the authors studied anxiety pre and post ET. Anxiety scores were not different in the two groups before and after ET. No difference in pregnancy and birth ratio was found in the two groups. Hypnosis during ET is as effective as diazepam in terms of pregnancy ratio and anxiolytic effects, but with fewer side effects and should be routinely available.

Lack of Association Between Maternal or Neonatal Vitamin D Status and Risk of Childhood Type 1 Diabetes: A Scandinavian Case-Cohort Study.

PubMed

Thorsen, Steffen U; Mårild, Karl; Olsen, Sjurdur F; Holst, Klaus K; Tapia, German; Granström, Charlotta; Halldorsson, Thorhallur I; Cohen, Arieh S; Haugen, Margaretha; Lundqvist, Marika; Skrivarhaug, Torild; Njølstad, Pål R; Joner, Geir; Magnus, Per; Størdal, Ketil; Svensson, Jannet; Stene, Lars C

2018-06-01

Studies on vitamin D status during pregnancy and risk of type 1 diabetes mellitus (T1D) lack consistency and are limited by small sample sizes or single measures of 25-hydroxyvitamin D (25(OH)D). We investigated whether average maternal 25(OH)D plasma concentrations during pregnancy are associated with risk of childhood T1D. In a case-cohort design, we identified 459 children with T1D and a random sample (n = 1,561) from the Danish National Birth Cohort (n = 97,127) and Norwegian Mother and Child Cohort Study (n = 113,053). Participants were born between 1996 and 2009. The primary exposure was the estimated average 25(OH)D concentration, based on serial samples from the first trimester until delivery and on umbilical cord plasma. We estimated hazard ratios using weighted Cox regression adjusting for multiple confounders. The adjusted hazard ratio for T1D per 10-nmol/L increase in the estimated average 25(OH)D concentration was 1.00 (95% confidence interval: 0.90, 1.10). Results were consistent in both cohorts, in multiple sensitivity analyses, and when we analyzed mid-pregnancy or cord blood separately. In conclusion, our large study demonstrated that normal variation in maternal or neonatal 25(OH)D is unlikely to have a clinically important effect on risk of childhood T1D.

Increased risk of lung cancer in patients with eczema: a nationwide cohort study in Taiwan.

PubMed

Juan, Chao-Kuei; Shen, Jui-Lung; Lin, Cheng-Li; Kim, Karen Wang; Chen, Wen-Chi

2016-09-01

The association between lung cancer and eczema remains controversial. Previous studies have yielded conflicting results. This retrospective population-based cohort study is aimed at clarifying the risk of lung cancer associated with eczema. By using the Taiwan National Health Insurance Research Database, we identified 43,719 patients who had been newly diagnosed with eczema in the years 2000 to 2010. The comparison cohort included 87,438 randomly selected, age-matched patients without eczema. The cases of these two cohorts were followed until 2011. The Cox proportional hazard regression model was used to calculate the risk of lung cancer in eczema patients. The database did not contain any information regarding smoking, alcohol consumption, socioeconomic status, or family history. After adjusting for age and comorbidity, the population with eczema had a 2.80-fold greater risk of developing lung cancer compared with the population in the comparison cohort (adjusted hazard ratio 2.80, 95 % confidence interval 2.59-3.03). Eczema patients with comorbid diseases including asthma, chronic obstructive -pulmonary disease, alcoholic liver damage, or diabetes were at a higher risk of lung cancer compared with the non-eczema patients without comorbidity. Eczema is associated with a greater risk for the development of lung cancer. Further studies with more comprehensive information on potential confounders are warranted. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Impact of Probiotics on Necrotizing Enterocolitis

PubMed Central

Underwood, Mark A.

2016-01-01

A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention. PMID:27836423

Risk of subsequent attention deficit-hyperactivity disorder in children with febrile seizures.

PubMed

Ku, Yi-Chia; Muo, Chih-Hsin; Ku, Chin-Shein; Chen, Chao-Huei; Lee, Wen-Yuan; Shen, Ein-Yiao; Chang, Yen-Jung; Kao, Chia-Hung

2014-04-01

In this study, we obtained relevant data from a nationwide cohort database to investigate the risk of attention deficit-hyperactivity disorder (ADHD) in children with a history of febrile seizures (FS). We identified 1081 children with FS as the case cohort, and the date of diagnosis was used as an index date. Four controls were matched randomly with each case based on age, sex, urbanisation level, parents' occupation, and index date. We applied Cox's proportional hazards regression to estimate the HR and CI of FS-associated ADHD. After 11 years of follow-up, the incidence of ADHD for the FS and control cohorts is 7.83 and 4.72 per 1000 person-years, respectively. The FS cohort was 1.66 times more at risk of ADHD occurrence (95% CI 1.27 to 2.18) than the control cohort. The risk of developing ADHD increased in conjunction with the frequency of FS-related visits. FS may increase the risk of subsequent ADHD occurrence in children. Children who visited physicians for FS more than twice had a significantly higher cumulative incidence of ADHD.

Prediction of Waitlist Mortality in Adult Heart Transplant Candidates: The Candidate Risk Score.

PubMed

Jasseron, Carine; Legeai, Camille; Jacquelinet, Christian; Leprince, Pascal; Cantrelle, Christelle; Audry, Benoît; Porcher, Raphael; Bastien, Olivier; Dorent, Richard

2017-09-01

The cardiac allocation system in France is currently based on urgency and geography. Medical urgency is defined by therapies without considering objective patient mortality risk factors. This study aimed to develop a waitlist mortality risk score from commonly available candidate variables. The study included all patients, aged 16 years or older, registered on the national registry CRISTAL for first single-organ heart transplantation between January 2010 and December 2014. This population was randomly divided in a 2:1 ratio into derivation and validation cohorts. The association of variables at listing with 1-year waitlist death or delisting for worsening medical condition was assessed within the derivation cohort. The predictors were used to generate a candidate risk score (CRS). Validation of the CRS was performed in the validation cohort. Concordance probability estimation (CPE) was used to evaluate the discriminative capacity of the models. During the study period, 2333 patients were newly listed. The derivation (n =1 555) and the validation cohorts (n = 778) were similar. Short-term mechanical circulatory support, natriuretic peptide decile, glomerular filtration rate, and total bilirubin level were included in a simplified model and incorporated into the score. The Concordance probability estimation of the CRS was 0.73 in the derivation cohort and 0.71 in the validation cohort. The correlation between observed and expected 1-year waitlist mortality in the validation cohort was 0.87. The candidate risk score provides an accurate objective prediction of waitlist mortality. It is currently being used to develop a modified cardiac allocation system in France.

Oral health in a life-course: birth-cohorts from 1929 to 2006 in Norway.

PubMed

Holst, D; Schuller, A A

2012-06-01

The purpose of the work was to study the influence of the oral health environment at age 10, of adolescent and adulthood dental behaviours and of social status on oral health of three birth-cohorts in 1983 and two of the three birth-cohorts in 2006 in Norway. The material comprised data from random samples of three birth-cohorts living in the counties of Sør- and Nord-Trøndelag in 1983. The birth-cohorts were 1929-1938, 1939-1948 and 1959-1960. In 2006 two samples were drawn from the 1929-1938 and 1959-1960 birth-cohort. The data collection comprised standard clinical measurements and self-administered questionnaires. The early oral health environment and social status and gender were related to oral health in 1983 by multiple regressions. The impact of social status was studied in combined datafiles from 1983 and 2006. The oral health environment in childhood was important for adults' oral health. The attention from parents and the local environment lead to a better oral health outcome in adulthood. Social status affected choices leading to better oral health. Regular dental visits were important especially for the eldest birth-cohort. Good oral health behaviours early and during adulthood were also important for oral health. Judged by number of tooth surfaces the difference between social status groups had not increased by 2006. A life-course perspective provides an opportunity to understand oral health over time. The present study supports the assumption that oral health is continuously exposed to environmental and behavioural risks that lead to accumulated diseases in the dental tissues.

Early Adult Outcomes of Adolescents Who Deliberately Poisoned Themselves

ERIC Educational Resources Information Center

Harrington, Richard; Pickles, Andrew; Aglan, Azza; Harrington, Val; Burroughs, Heather; Kerfoot, Michael

2006-01-01

Objective: To describe the early adult psychopathological and social outcomes of adolescents who deliberately poisoned themselves. Method: Prospective cohort study with a 6-year follow-up of 132 of 158 (84%) adolescents who, between ages 11 and 16 years, had taken part in a randomized trial of a brief family intervention after deliberate…

Theory-Driven Process Evaluation of a Complementary Feeding Trial in Four Countries

ERIC Educational Resources Information Center

Newman, Jamie E.; Garces, Ana; Mazariegos, Manolo; Hambidge, K. Michael; Manasyan, Albert; Tshefu, Antoinette; Lokangaka, Adrien; Sami, Neelofar; Carlo, Waldemar A.; Bose, Carl L.; Pasha, Omrana; Goco, Norman; Chomba, Elwyn; Goldenberg, Robert L.; Wright, Linda L.; Koso-Thomas, Marion; Krebs, Nancy F.

2014-01-01

We conducted a theory-driven process evaluation of a cluster randomized controlled trial comparing two types of complementary feeding (meat versus fortified cereal) on infant growth in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo. We examined process evaluation indicators for the entire study cohort (N = 1236) using chi-square…

Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

ERIC Educational Resources Information Center

Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

2009-01-01

Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

Efficacy of Rich Vocabulary Instruction in Fourth- and Fifth-Grade Classrooms

ERIC Educational Resources Information Center

Vadasy, Patricia F.; Sanders, Elizabeth A.; Logan Herrera, Becky

2015-01-01

A multi-cohort cluster randomized trial was conducted to estimate effects of rich vocabulary classroom instruction on vocabulary and reading comprehension. A total of 1,232 fourth- and fifth-grade students from 61 classrooms in 24 schools completed the study. Students received instruction in 140 Tier Two vocabulary words featured in two…

Impact of TimeSlips creative expression program on behavioral symptoms and psychotropic medication use in persons with dementia in long-term care: a cluster-randomized pilot study.

PubMed

Houser, Winona S; George, Daniel R; Chinchilli, Vernon M

2014-04-01

To evaluate whether involvement in TimeSlips, a creative storytelling program, reduced mood and behavioral symptoms as well as psychotropic medication use in persons with dementia. A cluster-randomized pilot study compared two discrete dementia care units in one nursing home. The control cohort (N = 10) received standard-of-care activity programming, and the intervention cohort (N = 10) received standard-of-care plus two one-hour TimeSlips sessions per week for six weeks. Data on mood and behavioral symptoms and psychotropic drug prescriptions were collected, and within-group and between-group comparisons were performed. Between-group comparisons did not reveal statistically significant differences in mood and behavioral symptoms. No differences in psychotropic drug prescriptions were found. Larger trials of longer duration are needed to determine whether involvement in TimeSlips reduces mood and behavioral symptoms that compromise quality of life for persons with dementia. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Ion channel gene expression predicts survival in glioma patients

PubMed Central

Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

2015-01-01

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. PMID:26235283

Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies.

PubMed

Aune, Dagfinn; Sen, Abhijit; Vatten, Lars J

2017-04-07

A history of hypertension has been associated with increased risk of endometrial cancer in several studies, but the results have not been consistent. We conducted a systematic review and meta-analysis of case-control and cohort studies to clarify the association between hypertension and endometrial cancer risk. PubMed and Embase databases were searched up to 27 th of February 2016. Prospective and case-control studies which reported adjusted relative risk estimates and 95% confidence intervals of endometrial cancer associated with a hypertension diagnosis were included. Summary relative risks were estimated using a random effects model. Nineteen case-control studies and 6 cohort studies were included. The summary RR was 1.61 (95% CI: 1.41-1.85, I 2  = 86%) for all studies, 1.73 (95% CI: 1.45-2.06, I 2  = 89%) for case-control studies and 1.32 (95% CI: 1.12-1.56, I 2  = 47%) for cohort studies. The association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for smoking, BMI, oral contraceptive use, and parity, compared to studies without such adjustment. This meta-analysis suggest an increased risk of endometrial cancer among patients with hypertension, however, further studies with more comprehensive adjustments for confounders are warranted to clarify the association.

Transmission parameters estimated for Salmonella typhimurium in swine using susceptible-infectious-resistant models and a Bayesian approach

PubMed Central

2014-01-01

Background Transmission models can aid understanding of disease dynamics and are useful in testing the efficiency of control measures. The aim of this study was to formulate an appropriate stochastic Susceptible-Infectious-Resistant/Carrier (SIR) model for Salmonella Typhimurium in pigs and thus estimate the transmission parameters between states. Results The transmission parameters were estimated using data from a longitudinal study of three Danish farrow-to-finish pig herds known to be infected. A Bayesian model framework was proposed, which comprised Binomial components for the transition from susceptible to infectious and from infectious to carrier; and a Poisson component for carrier to infectious. Cohort random effects were incorporated into these models to allow for unobserved cohort-specific variables as well as unobserved sources of transmission, thus enabling a more realistic estimation of the transmission parameters. In the case of the transition from susceptible to infectious, the cohort random effects were also time varying. The number of infectious pigs not detected by the parallel testing was treated as unknown, and the probability of non-detection was estimated using information about the sensitivity and specificity of the bacteriological and serological tests. The estimate of the transmission rate from susceptible to infectious was 0.33 [0.06, 1.52], from infectious to carrier was 0.18 [0.14, 0.23] and from carrier to infectious was 0.01 [0.0001, 0.04]. The estimate for the basic reproduction ration (R 0 ) was 1.91 [0.78, 5.24]. The probability of non-detection was estimated to be 0.18 [0.12, 0.25]. Conclusions The proposed framework for stochastic SIR models was successfully implemented to estimate transmission rate parameters for Salmonella Typhimurium in swine field data. R 0 was 1.91, implying that there was dissemination of the infection within pigs of the same cohort. There was significant temporal-cohort variability, especially at the susceptible to infectious stage. The model adequately fitted the data, allowing for both observed and unobserved sources of uncertainty (cohort effects, diagnostic test sensitivity), so leading to more reliable estimates of transmission parameters. PMID:24774444

Association of Traditional Chinese Medicine Therapy and the Risk of Vascular Complications in Patients With Type II Diabetes Mellitus

PubMed Central

Lee, Ai-Lin; Chen, Bor-Chyuan; Mou, Chih-Hsin; Sun, Mao-Feng; Yen, Hung-Rong

2016-01-01

Abstract With an increasing use of traditional Chinese medicine (TCM) in type 2 diabetes mellitus (T2DM), evidence of long-term benefit with adjunctive TCM treatment is limited. This study investigated whether the concurrent TCM treatment reduces the risk of vascular complications in T2DM patients by using a large population from National Health Insurance Research Database (NHIRD). We identified 33,457 adult patients with newly diagnosed T2DM using anti-diabetic agents from a random sample of one million beneficiaries in the NHIRD between January 1, 2000 and December 31, 2011. We recruited 1049 TCM users (received TCM over 30 days with a diagnosis of T2DM) and randomly selected 4092 controls as the non-TCM cohort at a ratio of 1:4 frequency-matched by age, sex, hypertension, hyperlipidemia, and index year. We investigated the prescription pattern of TCM and conducted a Cox proportional hazards regression to calculate the hazard ratios (HRs) of stroke, chronic kidney diseases (CKD), and diabetic foot between the 2 cohorts. In the TCM cohort, the prescription pattern of TCM was different between insulin and noninsulin patients. The most common herbs were Dan-Shen (Radix Salviae Miltiorrhizae) in noninsulin group and Da-Huang (Radix et Rhizoma Rhei) in insulin group. The most common formulae were Liu-Wei-Di-Huang-Wan in noninsulin group and Yu-Quan-Wan in insulin group. Although no significant reduction in the hazard ratio of CKD and diabetic foot, the incidence rate of stroke was 7.19 per 1000 person-years in the TCM cohort and 10.66 per 1000 person-years in the control cohort, respectively. After adjustment of age, sex, hypertension, hyperlipidemia, and antidiabetes agent use (including sulfonylureas, α-glucosidase, metformin, meglitinide, thiazolidinediones, and insulin), TCM cohorts were found to have a 33% decreased risk of stroke (95% CI = 0.46–0.97; P < 0.05). This population-based retrospective study showed that the complementary TCM therapy might associate with the decreased risk of stroke in T2DM, suggesting TCM as an adjunctive therapy for T2DM to prevent subsequent stroke. PMID:26817897

Dietary fat intake and ovarian cancer risk: a meta-analysis of epidemiological studies

PubMed Central

Qiu, Wenlong; Lu, Heng; Qi, Yana; Wang, Xiuwen

2016-01-01

Observational studies assessing the association of dietary fat and risk of ovarian cancer yield discrepant results. Pertinent prospective cohort studies were identified by a PubMed search from inception to December 2015. Sixteen independent case-control and nine cohort studies on dietary fat intake were included, with approximately 900,000 subjects in total. Relative risks (RRs) with 95% confidence intervals were pooled using a random effects model. Heterogeneity, sensitivity analysis and publication bias were assessed; subgroup analysis and analysis stratified by EOC histology were conducted. The reported studies showed a significant increase of ovarian cancer risk with high consumption of total-, saturated-, and trans-fats, while serous ovarian cancer was more susceptible to dietary fat consumption than other pathological subtypes. No evidence of positive association between dietary fat intake and ovarian cancer risk was provided by cohort studies. Menopausal status, hormone replacement therapy, body mass index (BMI), and pregnancy times, modified the objective associations. In conclusion, the meta-analysis findings indicate that high consumption of total, saturated and trans-fats increase ovarian cancer risk, and different histological subtypes have different susceptibility to dietary fat. PMID:27119509

Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.

PubMed

Austin, Peter C; Mamdani, Muhammad M; Juurlink, David N; Hux, Janet E

2006-09-01

To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.

Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study.

PubMed

Villumsen, Marie; Sørup, Signe; Jess, Tine; Ravn, Henrik; Relander, Thomas; Baker, Jennifer L; Benn, Christine Stabell; Sørensen, Thorkild I A; Aaby, Peter; Roth, Adam

2009-11-16

Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines. In a background cohort (N=47,622) from the Copenhagen School Health Records Register, cases of leukaemia (N=20) and lymphoma (N=51) were identified through the Danish Cancer Registry. The vaccination status of the cases was compared with the vaccination status of a 5% random sample (N=2073) of the background cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas.

Analysis of multivariate longitudinal kidney function outcomes using generalized linear mixed models.

PubMed

Jaffa, Miran A; Gebregziabher, Mulugeta; Jaffa, Ayad A

2015-06-14

Renal transplant patients are mandated to have continuous assessment of their kidney function over time to monitor disease progression determined by changes in blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR). Multivariate analysis of these outcomes that aims at identifying the differential factors that affect disease progression is of great clinical significance. Thus our study aims at demonstrating the application of different joint modeling approaches with random coefficients on a cohort of renal transplant patients and presenting a comparison of their performance through a pseudo-simulation study. The objective of this comparison is to identify the model with best performance and to determine whether accuracy compensates for complexity in the different multivariate joint models. We propose a novel application of multivariate Generalized Linear Mixed Models (mGLMM) to analyze multiple longitudinal kidney function outcomes collected over 3 years on a cohort of 110 renal transplantation patients. The correlated outcomes BUN, Cr, and eGFR and the effect of various covariates such patient's gender, age and race on these markers was determined holistically using different mGLMMs. The performance of the various mGLMMs that encompass shared random intercept (SHRI), shared random intercept and slope (SHRIS), separate random intercept (SPRI) and separate random intercept and slope (SPRIS) was assessed to identify the one that has the best fit and most accurate estimates. A bootstrap pseudo-simulation study was conducted to gauge the tradeoff between the complexity and accuracy of the models. Accuracy was determined using two measures; the mean of the differences between the estimates of the bootstrapped datasets and the true beta obtained from the application of each model on the renal dataset, and the mean of the square of these differences. The results showed that SPRI provided most accurate estimates and did not exhibit any computational or convergence problem. Higher accuracy was demonstrated when the level of complexity increased from shared random coefficient models to the separate random coefficient alternatives with SPRI showing to have the best fit and most accurate estimates.

Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline.

PubMed

Copeland, Kenneth C; Zeitler, Philip; Geffner, Mitchell; Guandalini, Cindy; Higgins, Janine; Hirst, Kathryn; Kaufman, Francine R; Linder, Barbara; Marcovina, Santica; McGuigan, Paul; Pyle, Laura; Tamborlane, William; Willi, Steven

2011-01-01

The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort represents the largest and best-characterized national sample of American youth with recent-onset type 2 diabetes. The objective of the study was to describe the baseline characteristics of participants in the TODAY randomized clinical trial. Participants were recruited over 4 yr at 15 clinical centers in the United States (n = 704) and enrolled, randomized, treated, and followed up 2-6 yr. The study was conducted at pediatric diabetes care clinics and practices. Eligible participants were aged 10-17 yr inclusive, diagnosed with type 2 diabetes for less than 2 yr and had a body mass index at the 85th percentile or greater. After baseline data collection, participants were randomized to one of the following groups: 1) metformin alone, 2) metformin plus rosiglitazone, or 3) metformin plus a lifestyle program of weight management. Baseline data presented include demographics, clinical/medical history, biochemical measurements, and clinical and biochemical abnormalities. At baseline the cohort included the following: 64.9% were female; mean age was 14.0 yr; mean diabetes duration was 7.8 months; mean body mass index Z-score was 2.15; 89.4% had a family history of diabetes; 41.1% were Hispanic, 31.5% were non-Hispanic black; 38.8% were living with both biological parents; 41.5% had a household annual income of less than $25,000; 26.3% had a highest education level of parent/guardian less than a high school degree; 26.3% had a blood pressure at the 90th percentile or greater; 13.6% had a blood pressure at the 95th percentile or greater; 13.0% had microalbuminuria; 79.8% had a low high-density lipoprotein level; and 10.2% had high triglycerides. The TODAY cohort is predominantly from racial/ethnic minority groups, with low socioeconomic status and a family history of diabetes. Clinical and biochemical abnormalities and comorbidities are prevalent within 2 yr of diagnosis. These findings contribute greatly to our understanding of American youth with type 2 diabetes.

Association between Kawasaki Disease and Autism: A Population-Based Study in Taiwan

PubMed Central

Kuo, Ho-Chang; Wu, Chung-Min; Chang, Wei-Pin; Kuo, Chun-Nan; Yeter, Deniz; Lin, Chun-Yi; Pai, Jei-Tsung; Chi, Ying-Chen; Lin, Chia-Hsien; Wang, Liang-Jen; Chang, Wei-Chiao

2014-01-01

Objective: The association between Kawasaki disease and autism has rarely been studied in Asian populations. By using a nationwide Taiwanese population-based claims database, we tested the hypothesis that Kawasaki disease may increase the risk of autism in Taiwan. Materials and Methods: Our study cohort consisted of patients who had received the diagnosis of Kawasaki disease (ICD-9-CM: 446.1) between 1997 and 2005 (N = 563). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 2,815). All subjects were tracked for 5 years from the date of cohort entry to identify whether they had developed autism (ICD-9-CM code 299.0) or not. Cox proportional hazard regressions were then performed to evaluate 5-year autism-free survival rates. Results: The main finding of this study was that patients with Kawasaki disease seem to not be at increased risk of developing autism. Of the total patients, four patients developed autism during the 5-year follow-up period, among whom two were Kawasaki disease patients and two were in the comparison cohort. Further, the adjusted hazard ratios (AHR) (AHR: 4.81; 95% confidence interval: 0.68–34.35; P = 0.117) did not show any statistical significance between the Kawasaki disease group and the control group during the 5-year follow-up. Conclusion: Our study indicated that patients with Kawasaki disease are not at increased risk of autism. PMID:24705358

Higher Strength Lanthanum Carbonate Provides Serum Phosphorus Control With a Low Tablet Burden and Is Preferred by Patients and Physicians: A Multicenter Study

PubMed Central

Mehrotra, Rajnish; Martin, Kevin J.; Fishbane, Steven; Sprague, Stuart M.; Zeig, Steven; Anger, Michael

2008-01-01

Background and objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. Design, setting, participants, & measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with ≤3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B. Results: At the end of week 4, 54% of patients achieved serum phosphorus control at dosages ≤3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication. Conclusions: Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden. PMID:18579668

Effects of Estrogen Receptor and Human Epidermal Growth Factor Receptor-2 Levels on the Efficacy of Trastuzumab: A Secondary Analysis of the HERA Trial.

PubMed

Loi, Sherene; Dafni, Urania; Karlis, Dimitris; Polydoropoulou, Varvara; Young, Brandon M; Willis, Scooter; Long, Bradley; de Azambuja, Evandro; Sotiriou, Christos; Viale, Giuseppe; Rüschoff, Josef; Piccart, Martine J; Dowsett, Mitch; Michiels, Stefan; Leyland-Jones, Brian

2016-08-01

A number of studies suggest that response to antihuman epidermal growth factor receptor-2 (currently known as ERBB2, butreferred to asHER2 in this study) agents differs by estrogen receptor (ER) level status. The clinical relevance of this is unknown. To determine the magnitude of trastuzumab benefit according to quantitative levels of ER and HER2 in the HERceptin Adjuvant (HERA) trial. The HERA trial was an international, multicenter, randomized trial that included 5099 patients with early-stage HER2-positive breast cancer, randomized between 2001 and 2005 to receive either no trastuzumab or trastuzumab, after adjuvant chemotherapy. This is a secondary analysis of the HERA study. Local ER immunohistochemical (IHC) analyses, HER2 fluorescence in situ hybridization (FISH) ratio, and copy number results were available for 3037 patients (59.6%) randomized to observation and trastuzumab (1 or 2 years) (cohort 1). Transcript levels of ESR1 and HER2 genes were available for 615 patients (12.1%) (cohort 2). Patients were randomized to receive either no trastuzumab or 1 year vs 2 years of trastuzumab. Endocrine therapy was given to patients with hormone receptor-positive disease as per local guidelines. Disease-free survival (DFS) and overall survival (OS) were the primary and secondary end points in the intent-to-treat population (ITT). Analyses adjusting for crossover (censored and inverse probability weighted [IPW]) were also performed. Interactions among treatment, ER status, and HER2 amplification using predefined cutoffs were assessed in Cox proportional hazards regression models. Median follow-up time was 8 years. Levels of FISH and HER2 copy numbers were significantly higher in ER-negative patients (P < .001). In cohort 1, for DFS and OS, a significant treatment effect was found for all ER, IHC, and FISH levels, except for the ER-positive/HER2 low FISH ratio (≥2 to <5) group (DFS: 3-way ITT Pvalue for interaction = .07; censored = .02; IPW = .03; OS ITT Pvalue for interaction = .007; censored = .04; IPW = .03). In cohort 2, consistent with cohort 1, a significant predictive effect of the ESR1 gene for both end points was also observed (DFS Pvalue for interaction = .06; OS = .02), indicating that breast cancers with higher ESR1 levels also derive less benefit from trastuzumab. Patients with HER2-positive breast cancers that are ER-positive by IHC analyses with low FISH ratio (≥2 to <5), or with higher ESR1 levels derive significantly less benefit from adjuvant trastuzumab after chemotherapy. These data may explain heterogeneity in response to anti-HER2 agents in HER2-positive, ER-positive breast cancers as some may be more luminal-like than HER2 driven. clinicaltrials.gov Identifier: NCT00045032.

Primary aldosteronism and thyroid disorders in atrial fibrillation: A Swedish nationwide case-control study.

PubMed

Mourtzinis, Georgios; Adamsson Eryd, Samuel; Rosengren, Annika; Björck, Lena; Adiels, Martin; Johannsson, Gudmundur; Manhem, Karin

2018-05-01

Background Atrial fibrillation is associated with hyperthyroidism. Patients with primary aldosteronism have an increased prevalence of atrial fibrillation. However, the prevalence of primary aldosteronism in the atrial fibrillation population is unknown. Aim This nationwide case-control study aimed to compare the prevalence of primary aldosteronism and thyroid disorders in patients with atrial fibrillation with that of age- and sex-matched controls. Methods We identified all atrial fibrillation cases in Sweden between 1987 and 2013 ( n = 713,569) by using the Swedish National Patient Register. A control cohort without atrial fibrillation was randomly selected from the Swedish Total Population Register with a case to control ratio of 1:2. This control cohort was matched for age, sex and place of birth ( n = 1,393,953). Results The prevalence of primary aldosteronism in December 2013 was 0.056% in the atrial fibrillation cohort and 0.024% in controls. At the same time, the prevalence of hypothyroidism was 5.9% in the atrial fibrillation cohort and 3.7% in controls. The prevalence of hyperthyroidism was 2.3% in the atrial fibrillation cohort and 0.8% in controls. Conclusion This study shows, for the first time, a doubled prevalence of primary aldosteronism in a large cohort of patients with atrial fibrillation compared with the general population. There is also an increased prevalence of hypo- and hyper-thyroidism in patients with atrial fibrillation compared with the general population.

Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.

PubMed

Santagostino, E; Pol, S; Olveira, A; Reesink, H W; van Erpecum, K; Bogomolov, P; Xu, D; Critelli, L; Srinivasan, S; Cooney, E

2016-09-01

This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants. Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts. Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC. © 2016 John Wiley & Sons Ltd.

Malignant transformation of Taiwanese patients with oral leukoplakia: A nationwide population-based retrospective cohort study.

PubMed

Wang, Tung-Yuan; Chiu, Yu-Wei; Chen, Yi-Tzu; Wang, Yu-Hsun; Yu, Hui-Chieh; Yu, Chuan-Hang; Chang, Yu-Chao

2018-05-01

Oral leukoplakia (OL) is one of the clinically diagnosed oral potentially malignant disorders (OPMDs) with an increased risk of oral cancer development. In this study, we investigated the malignant transformation of OL in Taiwanese population. A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort was randomly frequency-matched with the OL cohort according to age, sex, and index year. Oral submucous fibrosis (OSF) and oral lichen planus (OLP) were further stratified to evaluate the possible synergistic effects for OL-associated malignant transformation. In this cohort, 102 (5.374%) of 1898 OL patients were observed to transform into oral cancer. The malignant transformation rate was 26.40-fold in the OL cohort than in the comparison cohort after adjustment (95% confidence intervals 18.46-37.77). To further stratify with OSF and OLP, OL with OSF (58.38; 95% confidence intervals 34.61-98.50) and OL with OLP (36.88; 95% confidence intervals 8.90-152.78) had higher risk of malignant transformation rate than OL alone (27.01; 95% confidence intervals 18.91-38.59). The Kaplan-Meier plot revealed the free of malignant transformation rate was significant over the 13 years follow-up period (log-rank test, p < 0.001). OL patients exhibited a significantly higher risk of malignant transformation than those without OL. In addition, both OSF and OLP could enhance malignant transformation in patients with OL. However, further studies are required to identify the histopathological and clinical parameters in the pathogenesis of malignant transformation among OPMDs. Copyright © 2018. Published by Elsevier B.V.

Comparison of metal ion concentrations and implant survival after total hip arthroplasty with metal-on-metal versus metal-on-polyethylene articulations

PubMed Central

Dahlstrand, Henrik; Stark, André; Wick, Marius C; Anissian, Lucas; Hailer, Nils P; Weiss, Rüdiger J

2017-01-01

Background and purpose Large metal-on-metal (MoM) articulations are associated with metal wear and corrosion, leading to increased metal ion concentrations and unacceptable revision rates. There are few comparative studies of 28-mm MoM articulations with conventional metal-on-polyethylene (MoP) couplings. We present a long-term follow-up of a randomized controlled trial comparing MoM versus MoP 28-mm articulations, focused on metal ions and implant survival. Patients and methods 85 patients with a mean age of 65 years at surgery were randomized to a MoM (Metasul) or a MoP (Protasul) bearing. After 16 years, 38 patients had died and 4 had undergone revision surgery. 13 patients were unavailable for clinical follow-up, leaving 30 patients (n = 14 MoM and n = 16 MoP) for analysis of metal ion concentrations and clinical outcome. Results 15-year implant survival was similar in both groups (MoM 96% [95% CI 88–100] versus MoP 97% [95% CI 91–100]). The mean serum cobalt concentration was 4-fold higher in the MoM (1.5 μg/L) compared with the MoP cohort (0.4 μg/L, p < 0.001) and the mean chromium concentration was double in the MoM (2.2 μg/L) compared with the MoP cohort (1.0 μg/L, p = 0.05). Mean creatinine levels were similar in both groups (MoM 93 μmol/L versus MoP 92 μmol/L). Harris hip scores differed only marginally between the MoM and MoP cohorts. Interpretation This is the longest follow-up of a randomized trial on 28-mm MoM articulations, and although implant survival in the 2 groups was similar, metal ion concentrations remained elevated in the MoM cohort even in the long term. PMID:28699417

Crohn's disease and ulcerative colitis are associated with elevated standardized mortality ratios: a meta-analysis.

PubMed

Bewtra, Meenakshi; Kaiser, Lisa M; TenHave, Tom; Lewis, James D

2013-03-01

Evidence regarding all-cause and cause-specific mortality in inflammatory bowel disease (IBD) is conflicting, and debate exists over appropriate study design to examine these important outcomes. We conducted a comprehensive meta-analysis of all-cause and cause-specific mortality in both Crohn's disease (CD) and ulcerative colitis (UC), and additionally examined various effects of study design on this outcome. A systematic search of PubMed and EMBASE was conducted to identify studies examining mortality rates relative to the general population. Pooled summary standardized mortality ratios (SMR) were calculated using random effect models. Overall, 35 original articles fulfilled the inclusion and exclusion criteria, reporting all-cause mortality SMRs varying from 0.44 to 7.14 for UC and 0.71 to 3.20 for CD. The all-cause mortality summary SMR for inception cohort and population cohort UC studies was 1.19 (95% confidence interval, 1.06-1.35). The all-cause mortality summary SMR for inception cohort and population cohort CD studies was 1.38 (95% confidence interval, 1.23-1.55). Mortality from colorectal cancer, pulmonary disease, and nonalcoholic liver disease was increased, whereas mortality from cardiovascular disease was decreased. Patients with UC and CD have higher rates of death from all causes, colorectal-cancer, pulmonary disease, and nonalcoholic liver disease.

Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention.

PubMed

Thompson, Patricia; Roe, Denise J; Fales, Liane; Buckmeier, Julie; Wang, Fang; Hamilton, Stanley R; Bhattacharyya, Achyut; Green, Sylvan; Hsu, Chiu-Hsieh; Chow, H-H Sherry; Ahnen, Dennis J; Boland, C Richard; Heigh, Russell I; Fay, David E; Martinez, Maria Elena; Jacobs, Elizabeth; Ashbeck, Erin L; Alberts, David S; Lance, Peter

2012-12-01

COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported. ©2012 AACR

Antiplatelet Regimen for Patients With Breakthrough Strokes While on Aspirin: A Systematic Review and Meta-Analysis.

PubMed

Lee, Meng; Saver, Jeffrey L; Hong, Keun-Sik; Rao, Neal M; Wu, Yi-Ling; Ovbiagele, Bruce

2017-09-01

Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis. We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model. Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit. Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke. © 2017 American Heart Association, Inc.

Understanding trends in Australian alcohol consumption-an age-period-cohort model.

PubMed

Livingston, Michael; Raninen, Jonas; Slade, Tim; Swift, Wendy; Lloyd, Belinda; Dietze, Paul

2016-09-01

To decompose Australian trends in alcohol consumption into their age, period (survey year) and cohort (birth year/generation) components. In particular, we aimed to test whether recent declines in overall consumption have been influenced by reductions in drinking among recently born cohorts. Seven cross-sectional waves of the Australian National Drug Strategy Household Survey (1995-2013). Age, period and cohort effects were estimated using a linear and logistic cross-classified random-effects models (CCREMs). Australia A total of 124 440 Australians (69 193 females and 55 257 males), aged 14-79 years. Whether or not respondents consumed alcohol in the 12 months prior to the survey and, for those who did, the estimated volume of pure alcohol consumed, derived using standard quantity-frequency survey questions. Controlling for age and period effects, there was significant variation in drinking participation and drinking volume by birth cohort. In particular, male cohorts born between the 1965 and 1974 and female cohorts born between 1955 and 1974 reported higher rates of drinking participation (P < 0.05), while the most recent cohorts (born in the 1990s) had lower rates of participation (P < 0.01). Among drinkers, the most recently born cohort also had sharply lower average consumption volumes than older cohorts for both men and women (P < 0.01). Recent birth cohorts (born between 1995 and 1999) in Australia report significantly lower rates of both drinking participation and drinking volume than previous cohorts, controlling for their age distribution and overall changes in population drinking. These findings suggest that the recent decline in alcohol consumption in Australia has been driven by declines in drinking among these recently born cohorts. These trends are consistent with international shifts in youth drinking. © 2016 Society for the Study of Addiction.

Is a sleeve lobectomy significantly better than a pneumonectomy?

PubMed

Stallard, Joseph; Loberg, Anna; Dunning, Joel; Dark, John

2010-11-01

A best evidence topic was written according to a structured protocol. The question addressed was 'whether a sleeve lobectomy results in a better survival rate than a pneumonectomy in suitable patients?' Altogether, more than 327 papers were found using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude in the biggest meta-analysis of nearly 3000 patients, the five-year survival was 50% for sleeve lobectomy compared to 30% for pneumonectomy. Operative mortality was 3% vs. 6% for pneumonectomy, and locoregional recurrence was 17% vs. 30%. These results are broadly consistent across all the 13 cohort studies presented here many of which document a 20-year single centre experience or more. There are significant issues in all cohort studies on this subject as, due to their non-randomized nature, the reason for not performing a sleeve resection may well have been more advanced disease, which would necessarily mean that the pneumonectomy patients would have a lower expected survival and higher local recurrence. In addition, there have been many large cohort studies to date and thus no more are required, as future studies are unlikely to resolve this issue. Thus, the only study that would adequately correct for this issue would be a randomized trial, but to prove a 10% increase in five-year survival a 300 patient study would be needed. This is bigger than any study ever done in this area and as some centres took 30 years to collect these numbers of potential sleeve patients an RCT is not a realistic possibility. Therefore, we conclude that no more cohort studies should be performed, as the results will be consistent with the meta-analyses and an RCT to eliminate their bias is unattainable, and thus no more research should be done on this topic and surgeons should use the figures presented above and in more detail in this best evidence topic to govern their management in the future.

External validation of a risk assessment model for venous thromboembolism in the hospitalised acutely-ill medical patient (VTE-VALOURR).

PubMed

Mahan, Charles E; Liu, Yang; Turpie, A Graham; Vu, Jennifer T; Heddle, Nancy; Cook, Richard J; Dairkee, Undaleeb; Spyropoulos, Alex C

2014-10-01

Venous thromboembolic (VTE) risk assessment remains an important issue in hospitalised, acutely-ill medical patients, and several VTE risk assessment models (RAM) have been proposed. The purpose of this large retrospective cohort study was to externally validate the IMPROVE RAM using a large database of three acute care hospitals. We studied 41,486 hospitalisations (28,744 unique patients) with 1,240 VTE hospitalisations (1,135 unique patients) in the VTE cohort and 40,246 VTE-free hospitalisations (27,609 unique patients) in the control cohort. After chart review, 139 unique VTE patients were identified and 278 randomly-selected matched patients in the control cohort. Seven independent VTE risk factors as part of the RAM in the derivation cohort were identified. In the validation cohort, the incidence of VTE was 0.20%; 95% confidence interval (CI) 0.18-0.22, 1.04%; 95%CI 0.88-1.25, and 4.15%; 95%CI 2.79-8.12 in the low, moderate, and high VTE risk groups, respectively, which compared to rates of 0.45%, 1.3%, and 4.74% in the three risk categories of the derivation cohort. For the derivation and validation cohorts, the total percentage of patients in low, moderate and high VTE risk occurred in 68.6% vs 63.3%, 24.8% vs 31.1%, and 6.5% vs 5.5%, respectively. Overall, the area under the receiver-operator characteristics curve for the validation cohort was 0.7731. In conclusion, the IMPROVE RAM can accurately identify medical patients at low, moderate, and high VTE risk. This will tailor future thromboprophylactic strategies in this population as well as identify particularly high VTE risk patients in whom multimodal or more intensive prophylaxis may be beneficial.

Reduced frequency and severity of residential fires following delivery of fire prevention education by on-duty fire fighters: cluster randomized controlled study.

PubMed

Clare, Joseph; Garis, Len; Plecas, Darryl; Jennings, Charles

2012-04-01

In 2008, Surrey Fire Services, British Columbia, commenced a firefighter-delivered, door-to-door fire-prevention education and smoke alarm examination/installation initiative with the intention of reducing the frequency and severity of residential structure fires in the City of Surrey. High-risk zones within the city were identified and 18,473 home visits were undertaken across seven temporal delivery cohorts (13.8% of non-apartment dwellings in the city). The frequency and severity of fires pre- and post- the home visit intervention was examined in comparison to randomized high-risk cluster controls. Overall, the frequency of fires was found to have reduced in the city overall, however, the reduction in the intervention cohorts was significantly larger than for controls. Furthermore, when fires did occur within the intervention cohorts, smoke detectors were activated more frequently and the fires were confined to the object of origin more often post-home visits. No equivalent pattern was observed for the cluster control. On-duty fire fighters can reduce the frequency and severity of residential fires through targeted, door-to-door distribution of fire prevention education in high-risk areas. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Netherlands Cohort Study – Meat Investigation Cohort; a population-based cohort over-represented with vegetarians, pescetarians and low meat consumers

PubMed Central

2013-01-01

Background Vegetarian diets have been associated with lower risk of chronic disease, but little is known about the health effects of low meat diets and the reliability of self-reported vegetarian status. We aimed to establish an analytical cohort over-represented with vegetarians, pescetarians and 1 day/week meat consumers, and to describe their lifestyle and dietary characteristics. In addition, we were able to compare self-reported vegetarians with vegetarians whose status has been confirmed by their response on the extensive food frequency questionnaire (FFQ). Study methods Embedded within the Netherlands Cohort Study (n = 120,852; including 1150 self-reported vegetarians), the NLCS-Meat Investigation Cohort (NLCS-MIC) was defined by combining all FFQ-confirmed-vegetarians (n = 702), pescetarians (n = 394), and 1 day/week meat consumers (n = 1,396) from the total cohort with a random sample of 2–5 days/week- and 6–7 days/week meat consumers (n = 2,965 and 5,648, respectively). Results Vegetarians, pescetarians, and 1 day/week meat consumers had more favorable dietary intakes (e.g. higher fiber/vegetables) and lifestyle characteristics (e.g. lower smoking rates) compared to regular meat consumers in both sexes. Vegetarians adhered to their diet longer than pescetarians and 1 day/week meat consumers. 75% of vegetarians with a prevalent cancer at baseline had changed to this diet after diagnosis. 50% of self-reported vegetarians reported meat or fish consumption on the FFQ. Although the misclassification that occurred in terms of diet and lifestyle when merely relying on self-reporting was relatively small, the impact on associations with disease risk remains to be studied. Conclusion We established an analytical cohort over-represented with persons at the lower end of the meat consumption spectrum which should facilitate prospective studies of major cancers and causes of death using ≥20.3 years of follow-up. PMID:24289207

Long-term followup of a phase I/II randomized, placebo-controlled trial of palifermin to prevent graft-versus-host disease (GVHD) after related donor allogeneic hematopoietic cell transplantation (HCT)

PubMed Central

Levine, John E.; Blazar, Bruce R.; DeFor, Todd; Ferrara, James L.M.; Weisdorf, Daniel J.

2008-01-01

We previously conducted a randomized, double-blind, placebo-controlled study conducted from 2000–2003 of palifermin, a recombinant human keratinocyte growth factor, dosed from 240 mcg/kg to 720 mcg/kg, in 100 allogeneic hematopoietic stem cell transplantation (HCT) recipients. Treatment with palifermin showed beneficial effects on mucositis, but no significant effect on engraftment, acute GVHD, or early survival. In addition to the effect of palifermin on mucosa, other pleotrophic effects, including more rapid immune reconstitution, have been seen in experimental transplant models. Therefore, we investigated whether with longer follow-up we could detect additional differences between the palifermin treated and placebo cohorts. We found no differences in CMV or invasive fungal infections, chronic GVHD, or long-term survival between cohorts. We conclude that the benefits of palifermin appear to primarily be limited to ameliorating mucotoxicity when given to allogeneic HCT recipients. PMID:18721764

Improving ECG Competence in Medical Trainees in a UK District General Hospital

PubMed Central

McAloon, Christopher; Leach, Helen; Gill, Simrat; Aluwalia, Arun; Trevelyan, Jasper

2014-01-01

Background Competency in electrocardiogram (ECG) interpretation is central to undergraduate and postgraduate clinical training. Studies have demonstrated ECGs are interpreted sub-optimally. Our study compares the effectiveness of two learning strategies to improve competence and confidence. Method A 1-month prospective randomized study compared the strategies in two cohorts: undergraduate third year medical students and postgraduate foundation year one (FY1) doctors. Both had blinded randomization to one of these learning strategies: focused teaching program (FTP) and self-directed learning (SDL). All volunteers completed a confidence questionnaire before and after allocation learning strategy and an ECG recognition multiple choice question (MCQ) paper at the end of the learning period. Results The FTP group of undergraduates demonstrated a significant difference in successfully interpreting “ventricular tachycardia” (P = 0.046) and “narrow complex tachycardia” (P = 0.009) than the SDL group. Participant confidence increased in both learning strategies. FTP confidence demonstrated a greater improvement than SDL for both cohorts. Conclusion A dedicated teaching program can improve trainee confidence and competence in ECG interpretation. A larger benefit is observed in undergraduates and those undertaking a FTP. PMID:28392875

A primary health-care intervention on pre- and postnatal risk factor behavior to prevent childhood allergy. The Prevention of Allergy among Children in Trondheim (PACT) study.

PubMed

Storrø, Ola; Oien, Torbjørn; Dotterud, Christian K; Jenssen, Jon A; Johnsen, Roar

2010-07-28

This study aimed to evaluate the impact of a primary prevention intervention program on risk behavior for allergic diseases among children up to 2 years of age. The setting was in ordinary pre- and postnatal primary health care in Trondheim, Norway. The Prevention of Allergy among Children in Trondheim, Norway (PACT) study invited all pregnant women and parents to children up to 2 years of age in the community to participate in a non-randomized, controlled, multiple life-style intervention study. Interventional topics was increased dietary intake of cod liver oil and oily fish for women during pregnancy and for infants during the first 2 years of life, reduced parental smoking and reduced indoor dampness. A control cohort was established prior to the intervention cohort with "follow up as usual". Questionnaires were completed in pregnancy, 6 weeks after birth and at 1 and 2 years of age. Trends in exposure and behavior are described. Intake of oily fish and cod liver oil increased statistically significantly among women and infants in the intervention cohort compared to the control cohort. There was a low postnatal smoking prevalence in both cohorts, with a trend towards a decreasing smoking prevalence in the control cohort. There was no change in indoor dampness or in behavior related to non- intervened life-style factors. The dietary intervention seemed to be successful. The observed reduced smoking behavior could not be attributed to the intervention program, and the latter had no effect on indoor dampness. (Current Controlled Trials registration number: ISRCTN28090297).

Comparative effectiveness, safety and acceptability of medical abortion at home and in a clinic: a systematic review

PubMed Central

Park, Min Hae; Shakur, Haleema; Free, Caroline

2011-01-01

Abstract Objective To compare medical abortion practised at home and in clinics in terms of effectiveness, safety and acceptability. Methods A systematic search for randomized controlled trials and prospective cohort studies comparing home-based and clinic-based medical abortion was conducted. The Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE and Popline were searched. Failure to abort completely, side-effects and acceptability were the main outcomes of interest. Odds ratios and their 95% confidence intervals (CIs) were calculated. Estimates were pooled using a random-effects model. Findings Nine studies met the inclusion criteria (n = 4522 participants). All were prospective cohort studies that used mifepristone and misoprostol to induce abortion. Complete abortion was achieved by 86–97% of the women who underwent home-based abortion (n = 3478) and by 80–99% of those who underwent clinic-based abortion (n = 1044). Pooled analyses from all studies revealed no difference in complete abortion rates between groups (odds ratio = 0.8; 95% CI: 0.5–1.5). Serious complications from abortion were rare. Pain and vomiting lasted 0.3 days longer among women who took misoprostol at home rather than in clinic. Women who chose home-based medical abortion were more likely to be satisfied, to choose the method again and to recommend it to a friend than women who opted for medical abortion in a clinic. Conclusion Home-based abortion is safe under the conditions in place in the included studies. Prospective cohort studies have shown no differences in effectiveness or acceptability between home-based and clinic-based medical abortion across countries. PMID:21556304

The Quantitative Effect of Students Using Podcasts in a First Year Undergraduate Exercise Physiology Module

ERIC Educational Resources Information Center

Abt, Grant; Barry, Tim

2007-01-01

This study reports the quantitative effect of students using podcasts in a 1st year undergraduate exercise physiology module. From a cohort of 70 students, 50 volunteered and completed the study. Using a pre-post random allocation research design, students were allocated to either a podcast group (PG) or control group (CG) based on a 32-question…

Association between appendectomy and subsequent colorectal cancer development: an Asian population study.

PubMed

Wu, Shih-Chi; Chen, William Tzu-Liang; Muo, Chih-Hsin; Ke, Tao-Wei; Fang, Chu-Wen; Sung, Fung-Chang

2015-01-01

The appendix may modulate colon microbiota and bowel inflammation. We investigated whether appendectomy alters colorectal cancer risk. We identified a cohort of 75,979 patients who underwent appendectomy between 1997 and 1999 based on the insurance claims of Taiwan. A comparison cohort of 303,640 persons without appendectomy was selected randomly, frequency matched by age, sex, comorbidity and entry year was also selected. We monitored subsequent colorectal cancer development in both cohorts. The overall colorectal cancer incidence was 14% higher in the appendectomy patients than in the comparison cohort (p <0.05): the highest incidence was observed for rectal cancer, and the lowest incidence was observed for cancer of the cecum-ascending colon for both cohorts. Men were at higher risk than women. Subjects ≥ 60 years had an HR of 12.8 compared to those <60 years. The incidence of colorectal cancer was much higher in 1.5-3.5 years post appendectomy follow-up than for the comparisons (HR of 2.13). Patients who received an incidental appendectomy had an HR of 2.90 when compared to the comparisons. Results of our study suggest that appendectomy in patients with appendicitis is likely associated with the development of colorectal cancer in the post-surgery period.

Tubal anastomosis after previous sterilization: a systematic review.

PubMed

van Seeters, Jacoba A H; Chua, Su Jen; Mol, Ben W J; Koks, Carolien A M

2017-05-01

Female sterilization is one of the most common contraceptive methods. A small number of women, however, opt for reversal of sterilization procedures after they experience regret. Procedures can be performed by laparotomy or laparoscopy, with or without robotic assistance. Another commonly utilized alternative is IVF. The choice between surgery and IVF is often influenced by reimbursement politics for that particular geographic location. We evaluated the fertility outcomes of different surgical methods available for the reversal of female sterilization, compared these to IVF and assessed the prognostic factors for success. Two search strategies were employed. Firstly, we searched for randomized and non-randomized clinical studies presenting fertility outcomes of sterilization reversal up to July 2016. Data on the following outcomes were collected: pregnancy rate, ectopic pregnancy rate, cost of the procedure and operative time. Eligible study designs included prospective or retrospective studies, randomized controlled trials, cohort studies, case-control studies and case series. No age restriction was applied. Exclusion criteria were patients suffering from tubal infertility from any other reason (e.g. infection, endometriosis and adhesions from previous surgery) and studies including <10 participants. The following factors likely to influence the success of sterilization reversal procedures were then evaluated: female age, BMI and duration and method of sterilization. Secondly, we searched for randomized and non-randomized clinical studies that compared reversal of sterilization to IVF and evaluated them for pregnancy outcomes and cost effectiveness. We included 37 studies that investigated a total of 10 689 women. No randomized controlled trials were found. Most studies were retrospective cohort studies of a moderate quality. The pooled pregnancy rate after sterilization reversal was 42-69%, with heterogeneity seen from the different methods utilized. The reported ectopic pregnancy rate was 4-8%. The only prognostic factor affecting the chance of conception was female age. The surgical approach (i.e. laparotomy [microscopic], laparoscopy or robotic) had no impact on the outcome, with the exception of the macroscopic laparotomic technique, which had inferior results and is not currently utilized. For older women, IVF could be a more cost-effective alternative for the reversal of sterilization. However, direct comparative data are lacking and a cut-off age cannot be stated. In sterilized women who suffer regret, surgical tubal re-anastomosis is an effective treatment, especially in younger women. However, there is a need for randomized controlled trials comparing the success rates and costs of surgical reversal with IVF. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

What's in a Name? The Incorrect Use of Case Series as a Study Design Label in Studies Involving Dogs and Cats.

PubMed

Sargeant, J M; O'Connor, A M; Cullen, J N; Makielski, K M; Jones-Bitton, A

2017-07-01

Study design labels are used to identify relevant literature to address specific clinical and research questions and to aid in evaluating the evidentiary value of research. Evidence from the human healthcare literature indicates that the label "case series" may be used inconsistently and inappropriately. Our primary objective was to determine the proportion of studies in the canine and feline veterinary literature labeled as case series that actually corresponded to descriptive cohort studies, population-based cohort studies, or other study designs. Our secondary objective was to identify the proportion of case series in which potentially inappropriate inferential statements were made. Descriptive evaluation of published literature. One-hundred published studies (from 19 journals) labeled as case series. Studies were identified by a structured literature search, with random selection of 100 studies from the relevant citations. Two reviewers independently characterized each study, with disagreements resolved by consensus. Of the 100 studies, 16 were case series. The remaining studies were descriptive cohort studies (35), population-based cohort studies (36), or other observational or experimental study designs (13). Almost half (48.8%) of the case series or descriptive cohort studies, with no control group and no formal statistical analysis, included inferential statements about the efficacy of treatment or statistical significance of potential risk factors. Authors, peer-reviewers, and editors should carefully consider the design elements of a study to accurately identify and label the study design. Doing so will facilitate an understanding of the evidentiary value of the results. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Efficacy and Safety of Indacaterol/Glycopyrronium (IND/GLY) Versus Salmeterol/Fluticasone in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: The Chinese Cohort from the LANTERN Study.

PubMed

Zhong, Nanshan; Wang, Changzheng; Zhou, Xiangdong; Zhang, Nuofu; Humphries, Michael; Wang, Linda; Patalano, Francesco; Banerji, Donald

2016-12-01

Inhaled indacaterol/glycopyrronium fixed-dose combination (IND/GLY) is approved in over 80 countries, including the EU, Japan, Australia and Switzerland and the US. The LANTERN study evaluated the efficacy of IND/GLY compared with inhaled long-acting β 2 -agonist (LABA)/inhaled corticosteroid (ICS) or salmeterol/fluticasone (SFC) in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. Here we present the efficacy and safety of IND/GLY versus SFC in the Chinese cohort from the LANTERN study. LANTERN was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group study conducted in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. The patients were randomized (1:1) to once-daily IND/GLY (110/50 μg) or twice-daily SFC (50/500 μg). The primary endpoint was non-inferiority of IND/GLY versus SFC in terms of trough FEV 1 . Of the total 744 patients randomized in the LANTERN study, 598 (80.4%) were from Mainland China and randomized to IND/GLY (n = 298) or SFC (n = 300), and 553 (92.5%) completed the study. IND/GLY showed superiority over SFC with a statistically significant and clinically meaningful improvement in trough FEV 1 , FEV 1 AUC 0-4h , peak FEV 1 and trough forced vital capacity (FVC) change from the baseline. Annualized rate of moderate or severe COPD exacerbations was significantly lower (43%) with IND/GLY compared with SFC (rate ratio: 0.57, p = 0.015). Overall, adverse events were lower for IND/GLY (34.6%) versus SFC (43.1%). IND/GLY was superior in achieving bronchodilation versus SFC in a Chinese subgroup of patients from this study. Clinicaltrials.gov identifier: NCT01709903.

The HERrespect intervention to address violence against female garment workers in Bangladesh: study protocol for a quasi-experimental trial.

PubMed

Al Mamun, Mahfuz; Parvin, Kausar; Yu, Marat; Wan, Jessica; Willan, Samantha; Gibbs, Andrew; Jewkes, Rachel; Naved, Ruchira Tabassum

2018-04-18

Women in Bangladesh experience high rates of Intimate Partner Violence (IPV). IPV is more prevalent against income earning women compared to their non-earning counterparts, and Workplace Violence (WPV) is also common. Such violence is a violation of women's rights, and also constrains them from contributing to their personal growth, household, community and the economy at large. There is limited evidence on what works to prevent IPV and WPV amongst garment workers. This paper describes an evaluation of HERrespect, an intervention which aims to reduce IPV and WPV against female garment workers in and around Dhaka, Bangladesh. The trial employs a quasi-experimental design, with four intervention and four control factories. In the intervention factories a randomly selected cohort of married female line workers, a cohort of male line workers, and all middle management staff received the intervention. The intervention strategies involved (1) gender transformative group-based training for workers and management staff; (2) joint session between workers (15 female and male) and middle-management staff; (3) factory-wide activities; (4) awareness raising among top management; (5) factory policy review and development and 6) a community based campaign. For the evaluation, a cohort of randomly selected female workers and a cohort of selected management staff have been established. All workers (n = 800) and management staff (n = 395) from these cohorts were interviewed at baseline using two different questionnaires, and will be interviewed in the endline, 24 months post-baseline. Intention to treat analysis will be used for assessing the impact of HERrespect, comparing the intervention and control factories. To our knowledge this is the first study that seeks to evaluate the impact on IPV and WPV, of group sessions with female workers, male workers, and management; factory-wide campaigns and a community intervention among female garment workers in Bangladesh. Apart from informing programmers and policy makers about intervention effectiveness in reducing IPV and WPV against female garment workers this study will also present evidence on an intervention tailored to the situation in the garment sector, which makes HERrespect scalable. ClinicalTrials.gov NCT03304015, retrospectively registered on October 06, 2017.

Two-year changes in refractive error and related biometric factors in an adult Chinese population.

PubMed

He, Mingguang; Kong, Xiangbin; Chen, Qianyun; Zeng, Yangfa; Huang, Yuanzhou; Zhang, Jian; Morgan, Ian G; Meltzer, Mirjam E; Jin, Ling; Congdon, Nathan

2014-08-01

This article provides, to our knowledge, the first longitudinal population-based data on refractive error (RE) in Chinese persons. To study cohort effects and changes associated with aging in REs among Chinese adults. A 2-year, longitudinal population-based cohort study was conducted in southern China. Participants, identified using cluster random sampling, included residents of Yuexiu District, Guangzhou, China, aged 35 years or older who had undergone no previous eye surgery. Participants underwent noncycloplegic automated refraction and keratometry in December 2008 and December 2010; in a random 50% sample of the participants, anterior segment ocular coherence tomography measurement of lens thickness, as well as measurement of axial length and anterior chamber depth by partial coherence laser interferometry, were performed. Two-year change in spherical equivalent refraction (RE), lens thickness, axial length, and anterior chamber depth in the right eye. A total of 745 individuals underwent biometric testing in both 2008 and 2010 (2008 mean [SD] age, 52.2 [11.5] years; 53.7% women). Mean RE showed a 2-year hyperopic shift from -0.44 (2.21) to -0.31 (2.26) diopters (D) (difference, +0.13; 95% CI, 0.11 to 0.16). A consistent 2-year hyperopic shift of 0.09 to 0.22 D was observed among participants aged 35 to 64 years when stratifying by decade, suggesting that a substantial change in RE with aging may occur during this 30-year period. Cross-sectionally, RE increased only in the cohort younger than 50 years (0.11 D/y; 95% CI, 0.06 to 0.16). In the cross-sectional data, axial length decreased at -0.06 mm/y (95% CI, -0.09 to -0.04), although the 2-year change in axial length was positive and thus could not explain the cross-sectional difference. These latter results suggest a cohort effect, with greater myopia developing among younger persons. This first Chinese population-based longitudinal study of RE provides evidence for both important longitudinal aging changes and cohort effects, most notably greater myopia prevalence among younger persons.

Text messaging research participants as a follow-up strategy to decrease emergency department study attrition.

PubMed

Varner, Catherine; McLeod, Shelley; Nahiddi, Negine; Borgundvaag, Bjug

2018-01-01

Collecting patient-reported follow-up data for prospective studies in the emergency department (ED) is challenging in this minimal continuity setting. The objective of this study was to determine whether text messaging study participants involved in an ongoing randomized trial resulted in a lower rate of attrition as compared to conventional telephone follow-up. This was a nested cohort analysis of research participants enrolled in a randomized controlled trial assessing head injury discharge instructions. During the first 4 months of study follow-up, participants were contacted by a conventional telephone call. For the final 3 months, participants were contacted by text messaging following the first failed telephone attempt. A total of 118 patients were enrolled in the study (78 underwent conventional follow-up, and 40 received text messages). During the period of conventional follow-up, 3 participants withdrew from the study. Of the remaining 75 participants, 24 (32.0%) at 2 weeks and 32 (42.7%) at 4 weeks were unable to be contacted. Of the 40 participants receiving a reminder text message, 4 (10.0%) at 2 weeks and 10 (25.0%) at 4 weeks were unable to be contacted. Overall, text messaging study participants decreased attrition by 22% (95% CI: 5.9%, 34.7%) and 17.7% (95% CI: -0.8%, 33.3%) at 2- and 4-week follow-ups, respectively. In this ED cohort participating in a randomized trial, text message reminders of upcoming telephone follow-up interviews decreased the rate of attrition. Text messaging is a viable, low-cost communication strategy that can improve follow-up participation in prospective research studies.

Weight Gain Reduction Among 2-Year College Students: The CHOICES RCT

PubMed Central

Lytle, Leslie A.; Laska, Melissa N.; Linde, Jennifer A.; Moe, Stacey G.; Nanney, Marilyn S.; Hannan, Peter J.; Erickson, Darin J.

2016-01-01

Introduction The young adult years have been recognized as an influential period for excess weight gain. Non-traditional students and those attending 2-year community colleges are at particularly high risk for a range of adverse weight-related outcomes. Design Choosing Healthy Options in College Environments and Settings was an RCT with students randomly assigned into a control or intervention condition after baseline assessment. The study was designed to evaluate if a 24-month weight gain prevention intervention reduces the expected increase in BMI and overweight prevalence in young adults attending 2-year colleges. Two cohorts were recruited, corresponding to the fall and spring semesters. Data collection occurred at four time points for each cohort, with baseline occurring in fall 2011 for Cohort 1 and spring 2012 for Cohort 2. The 24-month follow-up occurred in fall 2013 for Cohort 1 and spring 2014 for Cohort 2. Data analysis occurred in 2015–2016. Setting/participants This research was conducted with 441 students from three community colleges in Minnesota. Intervention The 24-month intervention began with a 1-credit college course on healthy weight behaviors. A social networking and social support website was introduced as part of the course and participation encouraged for the duration of the trial. Main outcome measures Changes in BMI, weight, body fat percentage, waist circumference, and weight status were assessed. Results Retention of the cohorts at 24 months was 83.4%. There was not a statistically significant difference in BMI between conditions at the end of the trial. However, there was a statically significant difference in the prevalence of overweight/obesity between treatment conditions at 24 months. Also, participants randomized to the intervention who were overweight or obese at baseline were more than three times as likely to transition to a healthy weight by the end of the trial as compared with control students. Conclusions The intervention was not successful in achieving BMI differences between treatment groups. However, an 8% reduction in the prevalence of overweight and obesity over time may have population-level significance. PMID:27939237

Optimizing lay counsellor services for chronic care in South Africa: a qualitative systematic review.

PubMed

Petersen, Inge; Fairall, Lara; Egbe, Catherine O; Bhana, Arvin

2014-05-01

To conduct a qualitative systematic review on the use of lay counsellors in South Africa to provide lessons on optimizing their use for psychological and behavioural change counselling for chronic long-term care in scare-resource contexts. A qualitative systematic review of the literature on lay counsellor services in South Africa. Twenty-nine studies met the inclusion criteria. Five randomized control trials and two cohort studies reported that lay counsellors can provide behaviour change counselling with good outcomes. One multi-centre cohort study provided promising evidence of improved anti-retroviral treatment adherence and one non-randomized controlled study provided promising results for counselling for depression. Six studies found low fidelity of lay counsellor-delivered interventions in routine care. Reasons for low fidelity include poor role definition, inconsistent remuneration, lack of standardized training, and poor supervision and logistical support. Within resource-constrained settings, adjunct behaviour change and psychological services provided by lay counsellors can be harnessed to promote chronic care at primary health care level. Optimizing lay counsellor services requires interventions at an organizational level that provide a clear role definition and scope of practice; in-service training and formal supervision; and sensitization of health managers to the importance and logistical requirements of counselling. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study.

PubMed

Donneyong, Macarius M; Bykov, Katsiaryna; Bosco-Levy, Pauline; Dong, Yaa-Hui; Levin, Raisa; Gagne, Joshua J

2016-09-30

 To compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs.  Population based cohort study.  Five US databases covering individuals enrolled in private and public health insurance programs from 1995 to 2013.  Two cohorts of women who started taking tamoxifen. In cohort 1, women started taking an SSRI during tamoxifen treatment. In cohort 2, women were already taking an SSRI when they started taking tamoxifen.  All cause mortality in each cohort in women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine) versus other SSRIs. Propensity scores were used to match exposure groups in a variable ratio fashion. Results were measured separately for each cohort and combined hazard ratios calculated from Cox regression models across the two cohorts with random effects meta-analysis.  There were 6067 and 8465 new users of tamoxifen in cohorts 1 and 2, respectively. Mean age was 55. A total of 991 and 1014 deaths occurred in cohorts 1 and 2 during a median follow-up of 2.2 (interquartile range 0.9-4.5) and 2.0 (0.8-3.9) years, respectively. The pooled hazard ratio for death for potent inhibitors (rate 58.6/1000 person years) compared with other SSRIs (rate 57.9/1000 person years) across cohorts 1 and 2 was 0.96 (95% confidence interval 0.88 to 1.06). Results were consistent across sensitivity analyses.  Concomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Surgical versus Non-Operative Treatment for Lumbar Disc Herniation: Eight-Year Results for the Spine Patient Outcomes Research Trial (SPORT)

PubMed Central

Lurie, Jon D.; Tosteson, Tor D.; Tosteson, Anna N. A.; Zhao, Wenyan; Morgan, Tamara S.; Abdu, William A.; Herkowitz, Harry; Weinstein, James N.

2014-01-01

Study Design Concurrent prospective randomized and observational cohort studies. Objective To assess the 8-year outcomes of surgery vs. non-operative care. Summary of Background Data Although randomized trials have demonstrated small short-term differences in favor of surgery, long-term outcomes comparing surgical to non-operative treatment remain controversial. Methods Surgical candidates with imaging-confirmed lumbar intervertebral disc herniation meeting SPORT eligibility criteria enrolled into prospective randomized (501 participants) and observational cohorts (743 participants) at 13 spine clinics in 11 US states. Interventions were standard open discectomy versus usual non-operative care. Main outcome measures were changes from baseline in the SF-36 Bodily Pain (BP) and Physical Function (PF) scales and the modified Oswestry Disability Index (ODI - AAOS/Modems version) assessed at 6 weeks, 3 and 6 months, and annually thereafter. Results Advantages were seen for surgery in intent-to-treat analyses for the randomized cohort for all primary and secondary outcomes other than work status; however, with extensive non-adherence to treatment assignment (49% patients assigned to non-operative therapy receiving surgery versus 60% of patients assigned to surgery) these observed effects were relatively small and not statistically significant for primary outcomes (BP, PF, ODI). Importantly, the overall comparison of secondary outcomes was significantly greater with surgery in the intent-to-treat analysis (sciatica bothersomeness [p > 0.005], satisfaction with symptoms [p > 0.013], and self-rated improvement [p > 0.013]) in long-term follow-up. An as-treated analysis showed clinically meaningful surgical treatment effects for primary outcome measures (mean change Surgery vs. Non-operative; treatment effect; 95% CI): BP (45.3 vs. 34.4; 10.9; 7.7 to 14); PF (42.2 vs. 31.5; 10.6; 7.7 to 13.5) and ODI (−36.2 vs. −24.8; −11.2; −13.6 to −9.1). Conclusion Carefully selected patients who underwent surgery for a lumbar disc herniation achieved greater improvement than non-operatively treated patients; there was little to no degradation of outcomes in either group (operative and non-operative) from 4 to 8 years. PMID:24153171

Fitting parametric random effects models in very large data sets with application to VHA national data

PubMed Central

2012-01-01

Background With the current focus on personalized medicine, patient/subject level inference is often of key interest in translational research. As a result, random effects models (REM) are becoming popular for patient level inference. However, for very large data sets that are characterized by large sample size, it can be difficult to fit REM using commonly available statistical software such as SAS since they require inordinate amounts of computer time and memory allocations beyond what are available preventing model convergence. For example, in a retrospective cohort study of over 800,000 Veterans with type 2 diabetes with longitudinal data over 5 years, fitting REM via generalized linear mixed modeling using currently available standard procedures in SAS (e.g. PROC GLIMMIX) was very difficult and same problems exist in Stata’s gllamm or R’s lme packages. Thus, this study proposes and assesses the performance of a meta regression approach and makes comparison with methods based on sampling of the full data. Data We use both simulated and real data from a national cohort of Veterans with type 2 diabetes (n=890,394) which was created by linking multiple patient and administrative files resulting in a cohort with longitudinal data collected over 5 years. Methods and results The outcome of interest was mean annual HbA1c measured over a 5 years period. Using this outcome, we compared parameter estimates from the proposed random effects meta regression (REMR) with estimates based on simple random sampling and VISN (Veterans Integrated Service Networks) based stratified sampling of the full data. Our results indicate that REMR provides parameter estimates that are less likely to be biased with tighter confidence intervals when the VISN level estimates are homogenous. Conclusion When the interest is to fit REM in repeated measures data with very large sample size, REMR can be used as a good alternative. It leads to reasonable inference for both Gaussian and non-Gaussian responses if parameter estimates are homogeneous across VISNs. PMID:23095325

Student Mobility, Dosage, and Principal Stratification in School-Based RCTs

ERIC Educational Resources Information Center

Schochet, Peter Z.

2013-01-01

In school-based randomized control trials (RCTs), a common design is to follow student cohorts over time. For such designs, education researchers usually focus on the place-based (PB) impact parameter, which is estimated using data collected on all students enrolled in the study schools at each data collection point. A potential problem with this…

Knowledge about HIV and AIDS among Young South Africans in the Capricorn District, Limpopo Province

ERIC Educational Resources Information Center

Melwa, Irene T.; Oduntan, Olalekan A.

2012-01-01

Objective: To assess the basic knowledge about HIV and AIDS among young South Africans in the Capricorn District of Limpopo Province, South Africa. Design: A questionnaire-based cohort study, involving data collection from senior high school students. Setting: Randomly selected high schools in the Capricorn District, Limpopo Province, South…

Predicting School Readiness from Neurodevelopmental Assessments at Age 2 Years after Respiratory Distress Syndrome in Infants Born Preterm

ERIC Educational Resources Information Center

Patrianakos-Hoobler, Athena I.; Msall, Michael E.; Huo, Dezheng; Marks, Jeremy D.; Plesha-Troyke, Susan; Schreiber, Michael D.

2010-01-01

Aim: To determine whether neurodevelopmental outcomes at the age of 2 years accurately predict school readiness in children who survived respiratory distress syndrome after preterm birth. Method: Our cohort included 121 preterm infants who received surfactant and ventilation and were enrolled in a randomized controlled study of inhaled nitric…

Current Status of Renal Denervation in Hypertension.

PubMed

Briasoulis, Alexander; Bakris, George L

2016-11-01

Over the past 7 years, prospective cohorts and small randomized controlled studies showed that renal denervation therapy (RDN) in patients with resistant hypertension is safe but associated with variable effects on BP which are not substantially better than medical therapy alone. The failure of the most rigorously designed randomized sham-control study, SYMPLICITY HTN-3, to meet the efficacy endpoints has raised several methodological concerns. However, recently reported studies and ongoing trials with improved procedural characteristics, identification of patients with true treatment-resistant hypertension on appropriate antihypertensive regimens further explore potential benefits of RDN. The scope of this review is to summarize evidence from currently completed studies on RDN and discuss future perspectives of RDN therapy in patients with resistant hypertension.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. We conducted this systematic review to assess the efficacy and safety of FMT in UC. PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis

PubMed Central

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Background Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. Objective We conducted this systematic review to assess the efficacy and safety of FMT in UC. Data Sources PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. Data Extraction and Synthesis We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Results Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. Conclusion FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition. PMID:27295210

A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated With Development of Erectile Dysfunction Following Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerns, Sarah L.; Departments of Pathology and Genetics, Albert Einstein College of Medicine, Bronx, New York; Stock, Richard

2013-01-01

Purpose: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy. Methods and Materials: A 2-stage genome-wide association study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays. The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays. Results: Twelve SNPs identified in the discovery cohort and validated in themore » replication cohort were associated with development of ED following radiation therapy (Fisher combined P values 2.1 Multiplication-Sign 10{sup -5} to 6.2 Multiplication-Sign 10{sup -4}). Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and signaling) rather than DNA damage repair. In a multivariable model including nongenetic risk factors, the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status (Sommers' D P value = 1.7 Multiplication-Sign 10{sup -29}). A 1-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 (P value = 2.1 Multiplication-Sign 10{sup -19}). The cumulative SNP score model had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiation therapy planning stage. Conclusions: This genome-wide association study identified a set of SNPs that are associated with development of ED following radiation therapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.« less

Wine drinking and epithelial ovarian cancer risk: a meta-analysis

PubMed Central

Kim, Hee Seung; Shouten, Leo J.; Larsson, Susanna C.; Chung, Hyun Hoon; Kim, Yong Beom; Ju, Woong; Park, Noh Hyun; Song, Yong Sang; Kim, Seung Cheol; Kang, Soon-Beom

2010-01-01

Objective Wine has been the focus in the prevention of epithelial ovarian cancer (EOC) development because resveratrol abundant in wine has anti-carcinogenic properties. However, epidemiologic results have been heterogenous in the chemopreventive effect of wine on the development of EOC. Thus, we performed a meta-analysis for comparing EOC risk between wine and never drinkers using previous related studies. Methods After extensive search of the literature between January 1986 and December 2008, we analyzed 10 studies (3 cohort and 7 case control studies) with 135,871 women, who included 65,578 of wine and 70,293 of never drinkers. Results In all studies, there was no significant difference in EOC risk between wine and never drinkers (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.92 to 1.38; random effects). When we performed re-analysis according to the study design, 3 cohort and 7 case control studies showed that there were also no significant differences in EOC risk between wine and never drinkers, respectively (OR, 1.44 and 1.04; 95% CI, 0.74 and 2.82 and 0.88 to 1.22; random effects). In sub-analyses using 2 case-control studies, EOC risk was not different between former and never drinkers (OR, 1.12; 95% CI, 0.87 to 1.44; fixed effect), and between current and former drinkers (OR, 0.74; 95% CI, 0.41 to 1.34; random effects). Conclusion Although resveratrol, abundantly found in wine, is a promising naturally occurring compound with chemopreventive properties on EOC in preclinical studies, this meta-analysis suggests the epidemiologic evidence shows no association between wine drinking and EOC risk. PMID:20613902

Study design and hierarchy of evidence for surgical decision making.

PubMed

Sprague, Sheila; McKay, Paula; Thoma, Achilleas

2008-04-01

This article provides a historical overview of the hierarchy of evidence for surgical decision making and discusses key study designs in the hierarchy of evidence. This encompasses meta-analyses, randomized controlled trials, and observational studies, including cohort and case-controlled studies, case series and case reports, and basic science studies. This article also reviews the principles and importance of evidence-based plastic surgery and describes several systems to rate the strength of the scientific evidence.

Educational Differences in U.S. Adult Mortality: A Cohort Perspective

ERIC Educational Resources Information Center

Masters, Ryan K.; Hummer, Robert A.; Powers, Daniel A.

2012-01-01

We use hierarchical cross-classified random-effects models to simultaneously measure age, period, and cohort patterns of mortality risk between 1986 and 2006 for non-Hispanic white and non-Hispanic black men and women with less than a high school education, a high school education, and more than a high school education. We examine all-cause…

Vitamin C Intake and Pancreatic Cancer Risk: A Meta-Analysis of Published Case-Control and Cohort Studies.

PubMed

Hua, Yong-Fei; Wang, Gao-Qing; Jiang, Wei; Huang, Jing; Chen, Guo-Chong; Lu, Cai-De

2016-01-01

Observational studies inconsistently reported the relationship between vitamin C intake and risk of pancreatic cancer. We conducted a meta-analysis of published case-control and cohort studies to quantify the association. Potentially eligible studies were found on PubMed and EMBASE databases through May 31, 2015. A random-effects model was assigned to compute summary point estimates with corresponding 95% confidence intervals (CIs). Subgroup and meta-regression analyses were also performed to explore sources of heterogeneity. Our final analyses included 20 observational studies comprising nearly 5 thousand cases of pancreatic cancer. When comparing the highest with the lowest categories of vitamin C intake, the summary odds ratio/relative risk for case-control studies (14 studies), cohort studies (6 studies) and all studies combined was 0.58 (95% CI: 0.52-0.66), 0.93 (95% CI: 0.78-1.11) and 0.66 (95% CI: 0.58-0.75), respectively. The difference in the findings between case-control and cohort studies was statistically significant (P < .001). Possible publication bias was shown in the meta-analysis of case-control studies. There is insufficient evidence to conclude any relationship between vitamin C intake and risk of pancreatic cancer. The strong inverse association observed in case-control studies may be affected by biases (eg, recall and selection biases) that particularly affect case-control studies and/or potential publication bias. Future prospective studies of vitamin C intake and pancreatic cancer are needed.

Natural Language Processing for Asthma Ascertainment in Different Practice Settings.

PubMed

Wi, Chung-Il; Sohn, Sunghwan; Ali, Mir; Krusemark, Elizabeth; Ryu, Euijung; Liu, Hongfang; Juhn, Young J

We developed and validated NLP-PAC, a natural language processing (NLP) algorithm based on predetermined asthma criteria (PAC) for asthma ascertainment using electronic health records at Mayo Clinic. To adapt NLP-PAC in a different health care setting, Sanford Children Hospital, by assessing its external validity. The study was designed as a retrospective cohort study that used a random sample of 2011-2012 Sanford Birth cohort (n = 595). Manual chart review was performed on the cohort for asthma ascertainment on the basis of the PAC. We then used half of the cohort as a training cohort (n = 298) and the other half as a blind test cohort to evaluate the adapted NLP-PAC algorithm. Association of known asthma-related risk factors with the Sanford-NLP algorithm-driven asthma ascertainment was tested. Among the eligible test cohort (n = 297), 160 (53%) were males, 268 (90%) white, and the median age was 2.3 years (range, 1.5-3.1 years). NLP-PAC, after adaptation, and the human abstractor identified 74 (25%) and 72 (24%) subjects, respectively, with 66 subjects identified by both approaches. Sensitivity, specificity, positive predictive value, and negative predictive value for the NLP algorithm in predicting asthma status were 92%, 96%, 89%, and 97%, respectively. The known risk factors for asthma identified by NLP (eg, smoking history) were similar to the ones identified by manual chart review. Successful implementation of NLP-PAC for asthma ascertainment in 2 different practice settings demonstrates the feasibility of automated asthma ascertainment leveraging electronic health record data with a potential to enable large-scale, multisite asthma studies to improve asthma care and research. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Long-acting reversible contraceptive acceptability and unintended pregnancy among women presenting for short-acting methods: a randomized patient preference trial.

PubMed

Hubacher, David; Spector, Hannah; Monteith, Charles; Chen, Pai-Lien; Hart, Catherine

2017-02-01

Measures of contraceptive effectiveness combine technology and user-related factors. Observational studies show higher effectiveness of long-acting reversible contraception compared with short-acting reversible contraception. Women who choose long-acting reversible contraception may differ in key ways from women who choose short-acting reversible contraception, and it may be these differences that are responsible for the high effectiveness of long-acting reversible contraception. Wider use of long-acting reversible contraception is recommended, but scientific evidence of acceptability and successful use is lacking in a population that typically opts for short-acting methods. The objective of the study was to reduce bias in measuring contraceptive effectiveness and better isolate the independent role that long-acting reversible contraception has in preventing unintended pregnancy relative to short-acting reversible contraception. We conducted a partially randomized patient preference trial and recruited women aged 18-29 years who were seeking a short-acting method (pills or injectable). Participants who agreed to randomization were assigned to 1 of 2 categories: long-acting reversible contraception or short-acting reversible contraception. Women who declined randomization but agreed to follow-up in the observational cohort chose their preferred method. Under randomization, participants chose a specific method in the category and received it for free, whereas participants in the preference cohort paid for the contraception in their usual fashion. Participants were followed up prospectively to measure primary outcomes of method continuation and unintended pregnancy at 12 months. Kaplan-Meier techniques were used to estimate method continuation probabilities. Intent-to-treat principles were applied after method initiation for comparing incidence of unintended pregnancy. We also measured acceptability in terms of level of happiness with the products. Of the 916 participants, 43% chose randomization and 57% chose the preference option. Complete loss to follow-up at 12 months was <2%. The 12-month method continuation probabilities were 63.3% (95% confidence interval, 58.9-67.3) (preference short-acting reversible contraception), 53.0% (95% confidence interval, 45.7-59.8) (randomized short-acting reversible contraception), and 77.8% (95% confidence interval, 71.0-83.2) (randomized long-acting reversible contraception) (P < .001 in the primary comparison involving randomized groups). The 12-month cumulative unintended pregnancy probabilities were 6.4% (95% confidence interval, 4.1-8.7) (preference short-acting reversible contraception), 7.7% (95% confidence interval, 3.3-12.1) (randomized short-acting reversible contraception), and 0.7% (95% confidence interval, 0.0-4.7) (randomized long-acting reversible contraception) (P = .01 when comparing randomized groups). In the secondary comparisons involving only short-acting reversible contraception users, the continuation probability was higher in the preference group compared with the randomized group (P = .04). However, the short-acting reversible contraception randomized group and short-acting reversible contraception preference group had statistically equivalent rates of unintended pregnancy (P = .77). Seventy-eight percent of randomized long-acting reversible contraception users were happy/neutral with their initial method, compared with 89% of randomized short-acting reversible contraception users (P < .05). However, among method continuers at 12 months, all groups were equally happy/neutral (>90%). Even in a typical population of women who presented to initiate or continue short-acting reversible contraception, long-acting reversible contraception proved highly acceptable. One year after initiation, women randomized to long-acting reversible contraception had high continuation rates and consequently experienced superior protection from unintended pregnancy compared with women using short-acting reversible contraception; these findings are attributable to the initial technology and not underlying factors that often bias observational estimates of effectiveness. The similarly patterned experiences of the 2 short-acting reversible contraception cohorts provide a bridge of generalizability between the randomized group and usual-care preference group. Benefits of increased voluntary uptake of long-acting reversible contraception may extend to wider populations than previously thought. Copyright © 2016 Elsevier Inc. All rights reserved.

Coffee Drinking and the Risk of Endometrial Cancer: An Updated Meta-Analysis of Observational Studies.

PubMed

Lukic, Marko; Guha, Neela; Licaj, Idlir; van den Brandt, Piet A; Stayner, Leslie Thomas; Tavani, Alessandra; Weiderpass, Elisabete

2018-01-01

Several compounds contained in coffee have been found to suppress carcinogenesis in experimental studies. We conducted a dose-response meta-analysis to assess the impact of coffee consumption on the risk of endometrial cancer. We searched MEDLINE and EMBASE databases for studies published up to August 2016. Using random effects models, we estimated summary relative risks (RR) for cohort studies and odds ratios (OR) for case-control studies with 95% confidence intervals (CI). Dose-response analyses were conducted by using generalized least square trend estimation. We identified 12 cohort studies and 8 case-control studies eligible for inclusion, contributing with 11,663 and 2,746 endometrial cancer cases, respectively. The summary RR for highest compared with lowest coffee intake was 0.74 (95% CI: 0.68-0.81; p heterogeneity = 0.09, I 2 = 32%). The corresponding summary RR among cohort studies was 0.78 (95% CI: 0.71-0.85; p heterogeneity = 0.14, I 2 = 31.9%) and 0.63 (95% CI: 0.53-0.76; p heterogeneity = 0.57, I 2 = 0%) for case-control studies. One-cup increment per day was associated with 3% risk reduction (95% CI: 2-4%) in cohort studies and 12% (95% CI: 5-18%) in case-control studies. After pooling the results from 5 cohort studies, the association remained significant only in women with body mass index over 30 (RR = 0.71, 95% CI: 0.61-0.81). The results from our meta-analysis strengthen the evidence of a protective effect of coffee consumption on the risk of EC and further suggest that increased coffee intake might be particularly beneficial for women with obesity.

Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.

PubMed

Laporte, Silvy; Chapelle, Céline; Caillet, Pascal; Beyens, Marie-Noëlle; Bellet, Florelle; Delavenne, Xavier; Mismetti, Patrick; Bertoletti, Laurent

2017-04-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional magnetic resonance imaging of story listening in adolescents and young adults with Down syndrome: evidence for atypical neurodevelopment.

PubMed

Jacola, L M; Byars, A W; Hickey, F; Vannest, J; Holland, S K; Schapiro, M B

2014-10-01

Previous studies have documented differences in neural activation during language processing in individuals with Down syndrome (DS) in comparison with typically developing individuals matched for chronological age. This study used functional magnetic resonance imaging (fMRI) to compare activation during language processing in young adults with DS to typically developing comparison groups matched for chronological age or mental age. We hypothesised that the pattern of neural activation in the DS cohort would differ when compared with both typically developing cohorts. Eleven persons with DS (mean chronological age = 18.3; developmental age range = 4-6 years) and two groups of typically developing individuals matched for chronological (n = 13; mean age = 18.3 years) and developmental (mental) age (n = 12; chronological age range = 4-6 years) completed fMRI scanning during a passive story listening paradigm. Random effects group comparisons were conducted on individual maps of the contrast between activation (story listening) and rest (tone presentation) conditions. Robust activation was seen in typically developing groups in regions associated with processing auditory information, including bilateral superior and middle temporal lobe gyri. In contrast, the DS cohort demonstrated atypical spatial distribution of activation in midline frontal and posterior cingulate regions when compared with both typically developing control groups. Random effects group analyses documented reduced magnitude of activation in the DS cohort when compared with both control groups. Activation in the DS group differed significantly in magnitude and spatial extent when compared with chronological and mental age-matched typically developing control groups during a story listening task. Results provide additional support for an atypical pattern of functional organisation for language processing in this population. © 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Prevalence and characteristics of Shiga toxin-producing Escherichia coli in finishing pigs: Implications on public health.

PubMed

Cha, Wonhee; Fratamico, Pina M; Ruth, Leah E; Bowman, Andrew S; Nolting, Jacqueline M; Manning, Shannon D; Funk, Julie A

2018-01-02

Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, which can cause serious illnesses, including hemorrhagic colitis and hemolytic uremic syndrome. To study the epidemiology of STEC in finishing pigs and examine the potential risks they pose for human STEC infections, we conducted a longitudinal cohort study in three finishing sites. Six cohorts of pigs (2 cohorts/site, 20 pigs/cohort) were randomly selected, and fecal samples (n=898) were collected every two weeks through their finishing period. Eighty-two pigs (68.3%) shed STEC at least once, and the proportion of STEC-positive pigs varied across sites (50-97.5%) and cohorts (15-100%). Clinically important serotypes, O157:H7 (stx 2c , eae) and O26:H11 (stx 1a , eae), were recovered from two pigs at sites C and A, respectively. The most common serotype isolated was O59:H21 (stx 2e ), which was particularly prevalent in site B as it was recovered from all STEC positive pigs (n=39). Each cohort showed different patterns of STEC shedding, which were associated with the prevalent serotype. The median shedding duration of STEC in pigs was 28days, consistent with our prior study. However, among pigs shedding O59:H21 at least once, pigs in cohort B2 had a significantly longer shedding duration of 42days (P<0.05) compared to other cohorts. Stx2e was the most commonly observed stx variant in finishing pigs (93.9%), in accordance with the previous studies. Stx2e has been reported to be significantly associated with edema disease in pigs, however, the pathogenicity in humans warrants further investigations. Nonetheless, our findings affirm that pigs are an important reservoir for human STEC infections, and that the circulating serotypes in a cohort and site management factors may significantly affect the prevalence of STEC. Molecular characterization of STEC isolates and epidemiological studies to identify risk factors for shedding in pigs are strongly warranted to further address the significance to public health and to develop mitigation strategies. Copyright © 2017. Published by Elsevier B.V.

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies.

PubMed

Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira; Katsoulis, Michail; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Bueno-De-Mesquita, H Bas; Chong, Dawn Q; Jensen, Majken K; Wu, Chunsen; Overvad, Kim; Kühn, Tilman; Barrdahl, Myrto; Melander, Olle; Jirström, Karin; Peeters, Petra H; Sieri, Sabina; Panico, Salvatore; Cross, Amanda J; Riboli, Elio; Van Guelpen, Bethany; Myte, Robin; Huerta, José María; Rodriguez-Barranco, Miguel; Quirós, José Ramón; Dorronsoro, Miren; Tjønneland, Anne; Olsen, Anja; Travis, Ruth; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Severi, Gianluca; Bonet, Catalina; Palli, Domenico; Janke, Jürgen; Lee, Young-Ae; Boeing, Heiner; Giovannucci, Edward L; Ogino, Shuji; Fuchs, Charles S; Rimm, Eric; Wu, Kana; Chan, Andrew T; Pischon, Tobias

2017-05-01

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.

Perceived job insecurity as a risk factor for incident coronary heart disease: systematic review and meta-analysis.

PubMed

Virtanen, Marianna; Nyberg, Solja T; Batty, G David; Jokela, Markus; Heikkilä, Katriina; Fransson, Eleonor I; Alfredsson, Lars; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Casini, Annalisa; Clays, Els; De Bacquer, Dirk; Dragano, Nico; Elovainio, Marko; Erbel, Raimund; Ferrie, Jane E; Hamer, Mark; Jöckel, Karl-Heinz; Kittel, France; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Lunau, Thorsten; Madsen, Ida E H; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pahkin, Krista; Pejtersen, Jan H; Pentti, Jaana; Rugulies, Reiner; Salo, Paula; Shipley, Martin J; Siegrist, Johannes; Steptoe, Andrew; Suominen, Sakari B; Theorell, Töres; Toppinen-Tanner, Salla; Väänänen, Ari; Vahtera, Jussi; Westerholm, Peter J M; Westerlund, Hugo; Slopen, Natalie; Kawachi, Ichiro; Singh-Manoux, Archana; Kivimäki, Mika

2013-08-08

To determine the association between self reported job insecurity and incident coronary heart disease. A meta-analysis combining individual level data from a collaborative consortium and published studies identified by a systematic review. We obtained individual level data from 13 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. Four published prospective cohort studies were identified by searches of Medline (to August 2012) and Embase databases (to October 2012), supplemented by manual searches. Prospective cohort studies that reported risk estimates for clinically verified incident coronary heart disease by the level of self reported job insecurity. Two independent reviewers extracted published data. Summary estimates of association were obtained using random effects models. The literature search yielded four cohort studies. Together with 13 cohort studies with individual participant data, the meta-analysis comprised up to 174,438 participants with a mean follow-up of 9.7 years and 1892 incident cases of coronary heart disease. Age adjusted relative risk of high versus low job insecurity was 1.32 (95% confidence interval 1.09 to 1.59). The relative risk of job insecurity adjusted for sociodemographic and risk factors was 1.19 (1.00 to 1.42). There was no evidence of significant differences in this association by sex, age (<50 v ≥ 50 years), national unemployment rate, welfare regime, or job insecurity measure. The modest association between perceived job insecurity and incident coronary heart disease is partly attributable to poorer socioeconomic circumstances and less favourable risk factor profiles among people with job insecurity.

What Works Clearinghouse Quick Review of the Report "Exercise Improves Executive Function and Achievement and Alters Brain Activation in Overweight Children: A Randomized, Controlled Trial"

ERIC Educational Resources Information Center

What Works Clearinghouse, 2012

2012-01-01

The study examined whether exercise offered to sedentary, overweight children ages 7 to 11 improved executive function--defined as strategy execution when presented with a novel task--and academic performance in reading and math. The study authors analyzed data on about 170 students from Georgia who were recruited in five cohorts from 2003 to…

What Has Happened to Iowa's GED Graduates? A Two-, Five-, and Ten-Year Follow-Up Study. Final Report.

ERIC Educational Resources Information Center

Iowa State Dept. of Education, Des Moines. Div. of Community Colleges.

A longitudinal study was conducted to determine the short-term (2-year), intermediate (5-year), and long-term (10-year) impact of earning a high school equivalency diploma by taking the General Educational Development (GED) Tests in Iowa. The random sample of 2,500 GED graduates was drawn from each time cohort (individuals who had passed the GED…

Increased Risk of Restless Legs Syndrome in Patients With Migraine

PubMed Central

Yang, Fu-Chi; Lin, Te-Yu; Chen, Hsuan-Ju; Lee, Jiunn-Tay; Lin, Chun-Chieh; Huang, Wen-Yen; Chen, Hsin-Hung; Kao, Chia-Hung

2016-01-01

Abstract Previous studies suggest that an association between restless legs syndrome (RLS) and migraine exists. However, population-based data are unavailable in Asian cohorts. Our study thus aims to evaluate the association between migraine and RLS in a nationwide, population-based cohort in Taiwan and to examine the effects of age, sex, migraine subtype, and comorbidities on RLS development. Data from the Taiwan National Health Insurance Research Database were used. Patients aged 20 years or older with newly diagnosed migraine from 2000 to 2008 were included; 23,641 patients with newly diagnosed migraine and 94,564 subjects without migraine were randomly selected and followed until RLS development, withdrawal from the National Health Insurance, or until the end of 2011. A multivariate Cox proportional hazards regression model was used to explore the risk of RLS in patients with migraine after adjustment for demographic characteristics and comorbidities. Both cohorts were followed for a mean of 7.38 years. After adjustment for covariates, the risk of RLS was 1.42-fold higher (95% confidence interval = 1.13–1.79) in the migraine cohort than in the nonmigraine cohort (7.19 versus 3.42 years per 10,000 person-years). The increased risk was more prominent in males in the migraine cohort (1.87-fold increased risk, 95% confidence interval 1.22–2.85). Neither comorbidity status nor migraine subtype influenced the RLS risk. This population-based study demonstrated that migraine is associated with an increased risk of RLS compared with those without migraine, particularly in male patients with migraine and regardless of the comorbidity status. PMID:26844484

Validity of the estimates of oral cholera vaccine effectiveness derived from the test-negative design.

PubMed

Ali, Mohammad; You, Young Ae; Sur, Dipika; Kanungo, Suman; Kim, Deok Ryun; Deen, Jacqueline; Lopez, Anna Lena; Wierzba, Thomas F; Bhattacharya, Sujit K; Clemens, John D

2016-01-20

The test-negative design (TND) has emerged as a simple method for evaluating vaccine effectiveness (VE). Its utility for evaluating oral cholera vaccine (OCV) effectiveness is unknown. We examined this method's validity in assessing OCV effectiveness by comparing the results of TND analyses with those of conventional cohort analyses. Randomized controlled trials of OCV were conducted in Matlab (Bangladesh) and Kolkata (India), and an observational cohort design was used in Zanzibar (Tanzania). For all three studies, VE using the TND was estimated from the odds ratio (OR) relating vaccination status to fecal test status (Vibrio cholerae O1 positive or negative) among diarrheal patients enrolled during surveillance (VE= (1-OR)×100%). In cohort analyses of these studies, we employed the Cox proportional hazard model for estimating VE (=1-hazard ratio)×100%). OCV effectiveness estimates obtained using the TND (Matlab: 51%, 95% CI:37-62%; Kolkata: 67%, 95% CI:57-75%) were similar to the cohort analyses of these RCTs (Matlab: 52%, 95% CI:43-60% and Kolkata: 66%, 95% CI:55-74%). The TND VE estimate for the Zanzibar data was 94% (95% CI:84-98%) compared with 82% (95% CI:58-93%) in the cohort analysis. After adjusting for residual confounding in the cohort analysis of the Zanzibar study, using a bias indicator condition, we observed almost no difference in the two estimates. Our findings suggest that the TND is a valid approach for evaluating OCV effectiveness in routine vaccination programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case-control and cohort studies.

PubMed

Gariani, Karim; Mavrakanas, Thomas; Combescure, Christophe; Perrier, Arnaud; Marti, Christophe

2016-03-01

Diabetes mellitus is a well-established risk factor for atherosclerotic disease, but its role in the occurrence of venous thromboembolism (VTE) has not been elucidated. We conducted a meta-analysis of published cohort and case-control studies to assess whether diabetes mellitus is a risk factor for VTE. We systematically searched MEDLINE and EMBASE for case-control and prospective cohort studies assessing association between the risk of venous thromboembolism and diabetes. Odds ratios (OR) from case-control studies were combined while for prospective studies hazard ratios (HR) were combined. Models with random effects were used. Meta-analyses were conducted separately for raw and adjusted measures of association. 24 studies were identified including 10 cohort studies (274,501 patients) and 14 case-control studies (1,157,086 patients). Meta-analysis of the prospective cohort studies demonstrated a significant association between diabetes and VTE (HR 1.60; 95% CI 1.35 to 1.89). This association was no longer present after analysis of multi-adjusted HRs (HR 1.10; 95% CI 0.77 to 1.56). Meta-analysis of case-control studies showed a significant association between diabetes and VTE (OR 1.57; 95%CI 1.17 to 2.12), but this association was no longer present when adjusted ORs were used (OR 1.18; 95%CI 0.89 to 1.56). The increased risk of VTE associated with diabetes mainly results from confounders rather than an intrinsic effect of diabetes on venous thrombotic risk. Therefore, no specific recommendations should apply for the management of diabetic patients at risk for VTE. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Hierarchical Bayesian modeling of heterogeneous variances in average daily weight gain of commercial feedlot cattle.

PubMed

Cernicchiaro, N; Renter, D G; Xiang, S; White, B J; Bello, N M

2013-06-01

Variability in ADG of feedlot cattle can affect profits, thus making overall returns more unstable. Hence, knowledge of the factors that contribute to heterogeneity of variances in animal performance can help feedlot managers evaluate risks and minimize profit volatility when making managerial and economic decisions in commercial feedlots. The objectives of the present study were to evaluate heteroskedasticity, defined as heterogeneity of variances, in ADG of cohorts of commercial feedlot cattle, and to identify cattle demographic factors at feedlot arrival as potential sources of variance heterogeneity, accounting for cohort- and feedlot-level information in the data structure. An operational dataset compiled from 24,050 cohorts from 25 U. S. commercial feedlots in 2005 and 2006 was used for this study. Inference was based on a hierarchical Bayesian model implemented with Markov chain Monte Carlo, whereby cohorts were modeled at the residual level and feedlot-year clusters were modeled as random effects. Forward model selection based on deviance information criteria was used to screen potentially important explanatory variables for heteroskedasticity at cohort- and feedlot-year levels. The Bayesian modeling framework was preferred as it naturally accommodates the inherently hierarchical structure of feedlot data whereby cohorts are nested within feedlot-year clusters. Evidence for heterogeneity of variance components of ADG was substantial and primarily concentrated at the cohort level. Feedlot-year specific effects were, by far, the greatest contributors to ADG heteroskedasticity among cohorts, with an estimated ∼12-fold change in dispersion between most and least extreme feedlot-year clusters. In addition, identifiable demographic factors associated with greater heterogeneity of cohort-level variance included smaller cohort sizes, fewer days on feed, and greater arrival BW, as well as feedlot arrival during summer months. These results support that heterogeneity of variances in ADG is prevalent in feedlot performance and indicate potential sources of heteroskedasticity. Further investigation of factors associated with heteroskedasticity in feedlot performance is warranted to increase consistency and uniformity in commercial beef cattle production and subsequent profitability.

Testing the leadership and organizational change for implementation (LOCI) intervention in substance abuse treatment: a cluster randomized trial study protocol.

PubMed

Aarons, Gregory A; Ehrhart, Mark G; Moullin, Joanna C; Torres, Elisa M; Green, Amy E

2017-03-03

Evidence-based practice (EBP) implementation represents a strategic change in organizations that requires effective leadership and alignment of leadership and organizational support across organizational levels. As such, there is a need for combining leadership development with organizational strategies to support organizational climate conducive to EBP implementation. The leadership and organizational change for implementation (LOCI) intervention includes leadership training for workgroup leaders, ongoing implementation leadership coaching, 360° assessment, and strategic planning with top and middle management regarding how they can support workgroup leaders in developing a positive EBP implementation climate. This test of the LOCI intervention will take place in conjunction with the implementation of motivational interviewing (MI) in 60 substance use disorder treatment programs in California, USA. Participants will include agency executives, 60 program leaders, and approximately 360 treatment staff. LOCI will be tested using a multiple cohort, cluster randomized trial that randomizes workgroups (i.e., programs) within agency to either LOCI or a webinar leadership training control condition in three consecutive cohorts. The LOCI intervention is 12 months, and the webinar control intervention takes place in months 1, 5, and 8, for each cohort. Web-based surveys of staff and supervisors will be used to collect data on leadership, implementation climate, provider attitudes, and citizenship. Audio recordings of counseling sessions will be coded for MI fidelity. The unit of analysis will be the workgroup, randomized by site within agency and with care taken that co-located workgroups are assigned to the same condition to avoid contamination. Hierarchical linear modeling (HLM) will be used to analyze the data to account for the nested data structure. LOCI has been developed to be a feasible and effective approach for organizations to create a positive climate and fertile context for EBP implementation. The approach seeks to cultivate and sustain both effective general and implementation leadership as well as organizational strategies and support that will remain after the study has ended. Development of a positive implementation climate for MI should result in more positive service provider attitudes and behaviors related to the use of MI and, ultimately, higher fidelity in the use of MI. This study is registered with Clinicaltrials.gov ( NCT03042832 ), 2 February 2017, retrospectively registered.

Community-Based Interventions to Improve and Sustain Antiretroviral Therapy Adherence, Retention in HIV Care and Clinical Outcomes in Low- and Middle-Income Countries for Achieving the UNAIDS 90-90-90 Targets

PubMed Central

Adetokunboh, Olatunji; Uthman, Olalekan A.; Knowlton, Amy W.; Altice, Frederick L.; Schechter, Mauro; Galárraga, Omar; Geng, Elvin; Peltzer, Karl; Chang, Larry W.; Van Cutsem, Gilles; Jaffar, Shabbar S.; Ford, Nathan; Mellins, Claude A.; Remien, Robert H.; Mills, Edward J.

2017-01-01

Little is known about the effect of community versus health facility-based interventions to improve and sustain antiretroviral therapy (ART) adherence, virologic suppression, and retention in care among HIV-infected individuals in low-and middle-income countries (LMICs). We systematically searched four electronic databases for all available randomized controlled trials (RCTs) and comparative cohort studies in LMICs comparing community versus health facility-based interventions. Relative risks (RRs) for pre-defined adherence, treatment engagement (linkage and retention in care), and relevant clinical outcomes were pooled using random effect models. Eleven cohort studies and eleven RCTs (N = 97,657) were included. Meta-analysis of the included RCTs comparing community- versus health facility-based interventions found comparable outcomes in terms of ART adherence (RR = 1.02, 95 % CI 0.99 to 1.04), virologic suppression (RR = 1.00, 95 % CI 0.98 to 1.03), and all-cause mortality (RR = 0.93, 95 % CI 0.73 to 1.18). The result of pooled analysis from the RCTs (RR = 1.03, 95 % CI 1.01 to 1.06) and cohort studies (RR = 1.09, 95 % CI 1.03 to 1.15) found that participants assigned to community-based interventions had statistically significantly higher rates of treatment engagement. Two studies found community-based ART delivery model either cost-saving or cost-effective. Community- versus facility-based models of ART delivery resulted in at least comparable outcomes for clinically stable HIV-infected patients on treatment in LMICs and are likely to be cost-effective. PMID:27475643

POOLED ESTIMATES OF INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.

PubMed

Reibaldi, Michele; Pulvirenti, Alfredo; Avitabile, Teresio; Bonfiglio, Vincenza; Russo, Andrea; Mariotti, Cesare; Bucolo, Claudio; Mastropasqua, Rodolfo; Parisi, Guglielmo; Longo, Antonio

2018-01-01

To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review.

PubMed

Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

2010-04-01

After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was in the range of 1.3- to 2-fold greater. Preliminary data also indicate that the highest risk of stroke is related to the first weeks of treatment, and a risk profile for stroke is emerging, such as older age, cognitive impairment and vascular illness. Different pathophysiological pathways may be involved, ranging from the facilitation of thrombosis, pre-existing cardiovascular factors, sedation and a common diathesis for stroke of dementia, schizophrenia and affective illness. Before prescribing an antipsychotic, clinicians should weigh all the risk factors for a given patient and consider not only the indications as provided by the regulatory agencies, but also the overall effectiveness of typical and atypical antipsychotics.

Central venous access by trainees: a systematic review and meta-analysis of the use of simulation to improve success rate on patients.

PubMed

Madenci, Arin L; Solis, Carolina V; de Moya, Marc A

2014-02-01

Simulation training for invasive procedures may improve patient safety by enabling efficient training. This study is a meta-analysis with rigorous inclusion and exclusion criteria designed to assess the real patient procedural success of simulation training for central venous access. Published randomized controlled trials and prospective 2-group cohort studies that used simulation for the training of procedures involving central venous access were identified. The quality of each study was assessed. The primary outcome was the proportion of trainees who demonstrated the ability to successfully complete the procedure. Secondary outcomes included the mean number of attempts to procedural success and periprocedural adverse events. Proportions were compared between groups using risk ratios (RRs), whereas continuous variables were compared using weighted mean differences. Random-effects analysis was used to determine pooled effect sizes. We identified 550 studies, of which 5 (3 randomized controlled trials, 2 prospective 2-group cohort studies) studies of central venous catheter (CVC) insertion were included in the meta-analysis, composed of 407 medical trainees. The simulation group had a significantly larger proportion of trainees who successfully placed CVCs (RR, 1.09; 95% confidence interval [CI], 1.03-1.16, P<0.01). In addition, the simulation group had significantly fewer mean attempts to CVC insertion (weighted mean difference, -1.42; 95% CI, -2.34 to -0.49, P<0.01). There was no significant difference in the rate of adverse events between the groups (RR, 0.50; 95% CI, 0.19-1.29; P=0.15). Training programs should consider adopting simulation training for CVC insertion to improve the real patient procedural success of trainees.

Omega 3 fatty acids for prevention and treatment of cardiovascular disease

PubMed Central

Hooper, Lee; Harrison, Roger A; Summerbell, Carolyn D; Moore, Helen; Worthington, Helen V; Ness, Andrew; Capps, Nigel; Smith, George Davey; Riemersma, Rudolph; Ebrahim, Shah

2014-01-01

Background It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health. Objectives To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies. Search methods Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted. Selection criteria RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated. Data collection and analysis Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data. Main results Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats. Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes. Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded. Authors’ conclusions It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health. There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo. PMID:15495044

Cortisol Correlates with Severity of Illness and Poorly Reflects Adrenal Function in Pediatric Acute Respiratory Distress Syndrome.

PubMed

Yehya, Nadir; Vogiatzi, Maria G; Thomas, Neal J; Srinivasan, Vijay

2016-10-01

To test the association between random cortisol and severity of illness in a "real-world" application of current guidelines. We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels before potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 and ≥ 18 μg/dL, and hydrocortisone use and outcomes compared. Of 357 children with ARDS, 155 (15 nonsurvivors; 10%) had vasopressors initiated with cortisol drawn before possible hydrocortisone use. Patients with cortisol < 18 μg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum P < .05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 μg/dL. In patients with cortisol ≥ 18 μg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 μg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function. Copyright © 2016 Elsevier Inc. All rights reserved.

The Impact of Workers' Compensation on Outcomes of Surgical and Nonoperative Therapy for Patients with a Lumbar Disc Herniation SPORT

PubMed Central

Atlas, Steven J.; Tosteson, Tor D.; Blood, Emily A.; Skinner, Jonathan S.; Pransky, Glenn S.; Weinstein, James N.

2010-01-01

Study Design Prospective randomized and observational cohorts. Objective To compare outcomes of patients with and without workers' compensation who had surgical and nonoperative treatment for a lumbar intervertebral disc herniation (IDH). Summary of Background Data Few studies have examined the association between worker's compensation and outcomes of surgical and nonoperative treatment. Methods Patients with at least 6 weeks of sciatica and a lumbar IDH were enrolled in either a randomized trial or observational cohort at 13 US spine centers. Patients were categorized as workers' compensation or nonworkers' compensation based on baseline disability compensation and work status. Treatment was usual nonoperative care or surgical discectomy. Outcomes included pain, functional impairment, satisfaction and work/disability status at 6 weeks, 3, 6, 12, and 24 months. Results Combining randomized and observational cohorts, 113 patients with workers' compensation and 811 patients without were followed for 2 years. There were significant improvements in pain, function, and satisfaction with both surgical and nonoperative treatment in both groups. In the nonworkers' compensation group, there was a clinically and statistically significant advantage for surgery at 3 months that remained significant at 2 years. However, in the workers' compensation group, the benefit of surgery diminished with time; at 2 years no significant advantage was seen for surgery in any outcome (treatment difference for SF-36 bodily pain [−5.9; 95% CI: −16.7–4.9] and physical function [5.0; 95% CI: −4.9–15]). Surgical treatment was not associated with better work or disability outcomes in either group. Conclusion Patients with a lumbar IDH improved substantially with both surgical and nonoperative treatment. However, there was no added benefit associated with surgical treatment for patients with workers' compensation at 2 years while those in the nonworkers' compensation group had significantly greater improvement with surgical treatment. PMID:20023603

Electronic cigarettes as smoking cessation tool: are we there?

PubMed

Ghosh, Sohini; Drummond, M Bradley

2017-03-01

Electronic cigarette (e-cigarette) use is rapidly increasing, with many users reporting trying e-cigarettes as a method to quit combustible cigarettes. This review highlights recently published studies assessing the use of e-cigarettes as a tool for cessation of combustible cigarettes. When evaluating data from four randomized controlled trials and multiple cohort studies, differential association between e-cigarette use and cessation rates was seen. Cessation rates are highest in UK cohort studies and in studies using a multifaceted approach, such as with the addition of varenicline. The largest evidence base is derived from observational cohort studies. Overall, the current evidence remains too small for conclusive results regarding efficacy of e-cigarettes for combustible cessation. There does appear to be a consistent reduction in daily combustible cigarette use in regular e-cigarette users. Currently, there are conflicting data which can be used to support or dismiss e-cigarettes as a tool for smoking cessation. As larger population-based studies become available, the potential harms and benefits of e-cigarettes will become clearer. In the short term, shared decision-making with combustible cigarette users will be imperative when considering e-cigarettes as a smoking cessation tool.

Effects of Physical Activity on Cancer Survival: A Systematic Review

PubMed Central

Barbaric, Mary; Brooks, Eleanor; Moore, Lisa

2010-01-01

ABSTRACT Purpose: Physical activity (PA) has been suggested to help increase the survival of individuals with cancer. The objective of this review was to systematically evaluate and summarize the available evidence investigating the effect of PA on the survival of individuals with cancer. Methods: Electronic databases (CINAHL, EMBASE, and MEDLINE) were systematically searched for randomized controlled trials and cohort studies. Selected studies were assessed by two independent investigators for methodological quality, using the PEDro scale. Results: Ten prospective cohort studies met the inclusion criteria. Quality-assessment scores averaged 5/10 on the PEDro scale, with two articles obtaining a score of 6/10. The majority of studies found that individuals participating in higher levels of physical activity had a reduced risk of cancer-related mortality. This trend was observed specifically for breast, colon, and colorectal cancers. On average, it appears that engaging in higher levels of metabolic equivalent hours per week may help to improve survival rates among individuals diagnosed with cancer. Conclusion: Patients diagnosed with cancer demonstrated a trend toward increased survival with greater levels of PA. However, because only prospective cohort studies were included in the study, the conclusions drawn should be regarded with caution. PMID:21197176

Screening for Prostate Cancer Starting at Age 50-54. A Population-based Cohort Study

PubMed Central

Carlsson, Sigrid; Assel, Melissa; Ulmert, David; Gerdtsson, Axel; Hugosson, Jonas; Vickers, Andrew; Lilja, Hans

2016-01-01

Background Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective To evaluate the effect of prostate-specific antigen (PSA) screening, versus zero screening, starting at age 50-54, on prostate cancer mortality. Design, Setting, and Participants This is a population-based cohort study comparing 3,479 men aged 50 through 54 randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4,060 unscreened men aged 51 to 55 providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982-1985. Outcome measures and Statistical Analysis Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and Limitation At 17 years, regular PSA-screening in Göteborg of men in their early 50s carried a more than 2-fold higher risk of prostate cancer diagnosis compared to the unscreened men in Malmö (IRR 2.56, 95% CI 2.18, 3.02), but resulted in a substantial decrease in risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10,000 men (95% CI 22, 92) in the screened group. At 17 years, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of two different birth cohorts. Conclusions PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54, with NNI and NND comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55-69 years, at similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50-54. Trial registration The Göteborg randomized population-based prostate cancer screening trial is registered with the ISRCTN registry (isrctn.com). Identifier: ISRCTN54449243. PMID:27084245

Benefits of the Mediterranean diet beyond the Mediterranean Sea and beyond food patterns.

PubMed

Martínez-González, Miguel A

2016-10-14

Abundant and growing evidence has accrued to demonstrate that the traditional Mediterranean diet is likely to be the ideal dietary pattern for the prevention of cardiovascular disease. A landmark randomized trial (PREDIMED) together with many well-conducted long-term observational prospective cohort studies support this causal effect.A new, large British cohort study by Tong et al. assessing the association between adherence to the Mediterranean diet and cardiovascular disease was recently published in BMC Medicine. Using a superb methodology, they followed-up 23,902 participants for 12.2 years on average and observed several thousand incident cases.The results of this cohort study showed a significant beneficial effect of the Mediterranean diet on cardiovascular events. These findings support the transferability of this dietary pattern beyond the shores of the Mediterranean Sea. The authors provided measures of population impact in cardiovascular prevention and estimated that 19,375 cases of cardiovascular death would be prevented each year in the UK by promoting the Mediterranean Diet.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0677-4 .

The Prevalence of Mental Health Problems in Children 1 1/2 Years of Age--The Copenhagen Child Cohort 2000

ERIC Educational Resources Information Center

Skovgaard, Anne Mette; Houmann, Tine; Christiansen, Eva; Landorph, Susanne; Jorgensen, Torben; Olsen, E. M.; Heering, K.; Kaas-Nielsen, S.; Samberg, V.; Lichtenberg, A.

2007-01-01

Background: The Copenhagen Child Cohort, CCC 2000, was established to investigate developmental psychopathology prospectively from birth in a general population. Methods: A random sample of 211 children from the CCC 2000 was investigated when the children were 1 1/2 years of age. The prevalence and associates of mental health problems and…

Contemporary Options for Longitudinal Follow-Up: Lessons Learned from a Cohort of Urban Adolescents

ERIC Educational Resources Information Center

Tobler, Amy L.; Komro, Kelli A.

2011-01-01

This study reports efforts to locate and survey participants in Project Northland Chicago (PNC), a longitudinal, group-randomized trial of an alcohol preventive intervention for racial/ethnic minority, urban, early-adolescents, 3-4 years following the end of the intervention. Data were collected annually among students from 6th-8th grade and then…

Co-Occurring Trajectories of Symptoms of Anxiety, Depression, and Oppositional Defiance from Adolescence to Young Adulthood

ERIC Educational Resources Information Center

Leadbeater, Bonnie; Thompson, Kara; Gruppuso, Vincenza

2012-01-01

This study uses a cohort-sequential longitudinal design to examine the patterns of change and codevelopment of anxiety, depression, and oppositional defiant symptoms (ODS) from late adolescence to young adulthood. Four waves of data were collected biennially by individual interview with a random, community-based sample of 662 youth ages 12 to 18…

Parent Involvement and Child Development: First-Year Results from a School-Randomized Trial in Latino Communities

ERIC Educational Resources Information Center

Gamoran, Adam; Turley, Ruth Lopez; Turner, Alyn; Fish, Rachel

2010-01-01

The purpose of this study is to test the effects on children's social, behavioral, and academic outcomes of an intervention, Families and Schools Together (FAST), when implemented in two novel ways: (a) in schools with predominantly Latino children and (b) on an entire grade-level cohort instead of with individual families targeted for the…

Head Start FACES 2000: A Whole-Child Perspective on Program Performance. Fourth Progress Report.

ERIC Educational Resources Information Center

Zill, Nicholas; Resnick, Gary; Kim, Kwang; O'Donnell, Kevin; Sorongon, Alberto; McKey, Ruth Hubbell; Pai-Samant, Shefali; Clark, Cheryl; O'Brien, Robert; D'Elio, Mary Ann

In 1997, Head Start launched the Family and Child Experiences Survey (FACES), a study of a national random sample of Head Start programs, designed to describe characteristics, experiences, and outcomes for children and families served by Head Start. In 2000, FACES began data collection on a new national cohort of 2,800 children and their families…

Comparison of topical versus intravenous tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized controlled and prospective cohort trials.

PubMed

Wang, Hao; Shen, Bin; Zeng, Yi

2014-12-01

There has been much debate and controversy about the optimal regimen of tranexamic acid in primary total knee arthroplasty. The purpose of this study was to undertake a meta-analysis to compare the efficacy of topical and intravenous regimen of tranexamic acid in primary total knee arthroplasty. A systematic review of the electronic databases PubMed, CENTRAL, Web of Science, and Embase was undertaken. All randomized controlled trials and prospective cohort studies evaluating the effectiveness of topical and intravenous tranexamic acid during primary total knee arthroplasty were included. The focus of the analysis was on the outcomes of blood loss, transfusion rate, and thromboembolic complications. Subgroup analysis was performed when possible. Of 328 papers identified, six trials were eligible for data extraction and meta-analysis comprising 679 patients (739 knees). We found no statistically significant difference between topical and intravenous administration of tranexamic acid in terms of blood loss, transfusion requirements and thromboembolic complications. Topical tranexamic acid has a similar efficacy to intravenous tranexamic acid in reducing both blood loss and transfusion rate without sacrificing safety in primary total knee arthroplasty. II. Copyright © 2014 Elsevier B.V. All rights reserved.

Moving a randomized clinical trial into an observational cohort.

PubMed

Goodman, Phyllis J; Hartline, Jo Ann; Tangen, Catherine M; Crowley, John J; Minasian, Lori M; Klein, Eric A; Cook, Elise D; Darke, Amy K; Arnold, Kathryn B; Anderson, Karen; Yee, Monica; Meyskens, Frank L; Baker, Laurence H

2013-02-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute (NCI) and conducted by the Southwest Oncology Group (SWOG). A total of 35,533 men were assigned randomly to one of the four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, and placebo + placebo). The independent Data and Safety Monitoring Committee (DSMC) recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-Up (CFU) study. The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada, and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants. At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of 31 December 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site institutional review boards (IRBs). However, from this cohort, we estimate that an additional 580 prostate cancer cases and 215 Gleason 7 or higher grade cancers will be identified. Over 109,000 individual items have been mailed to participants. Active SELECT ancillary studies have continued. The substantial SELECT biorepository is available to researchers; requests to use the specimens are reviewed for feasibility and scientific merit. As of April 2012, 12 proposals had been approved. The accrual goal of the follow-up study was not met, limiting our power to address the study objectives satisfactorily. The CFU study is also dependent on a number of factors including continued funding, continued interest of investigators in the biorepository, and the continued contribution of the participants. Our experience may be less pertinent to investigators who wish to follow participants in a treatment trial or participants in prevention trials in other medical areas. Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up.

Moving a Randomized Clinical Trial into an Observational Cohort

PubMed Central

Goodman, Phyllis J.; Hartline, Jo Ann; Tangen, Catherine M.; Crowley, John J.; Minasian, Lori M.; Klein, Eric A.; Cook, Elise D.; Darke, Amy K.; Arnold, Kathryn B.; Anderson, Karen; Yee, Monica; Meyskens, Frank L.; Baker, Laurence H.

2013-01-01

Background The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo. The independent Data and Safety Monitoring Committee recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. Purpose A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-up (CFU) study. Methods The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants. Results At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of December 31, 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site IRBs. However, from this cohort we estimate that an additional 580 prostate cancer cases and 215 Gleason 7 or higher cancers will be identified. Over 109,000 individual items have been mailed to participants. Active SELECT ancillary studies have continued. The substantial SELECT biorepository is available to researchers; requests to use the specimens are reviewed for feasibility and scientific merit. As of April 2012, 12 proposals had been approved. Limitations The accrual goal of the follow-up study was not met, limiting our power to address the study objectives satisfactorily. The CFU study is also dependent on a number of factors including continued funding, continued interest of investigators in the biorepository and the continued contribution of the participants. Our experience may be less pertinent to investigators who wish to follow participants in a treatment trial or participants in prevention trials in other medical areas. Conclusions Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up. PMID:23064404

Association Between Random Measured Glucose Levels in Middle and Old Age and Risk of Dementia-Related Death.

PubMed

Rosness, Tor Atle; Engedal, Knut; Bjertness, Espen; Strand, Bjørn Heine

2016-01-01

To investigate the association between random measured glucose levels in middle and old age and dementia-related death. Population-based cohort study. Norwegian Counties Study (middle-aged individuals; 35-49) and Cohort of Norway participants (older individuals; 65-80). Individuals without (n=74,630) and with (n=3,095) known diabetes mellitus (N=77,725); 67,865 without and 2,341 with diabetes mellitus were included in the complete case analyses (nonmissing for all included covariates), of whom 1,580 without and 131 with diabetes mellitus died from dementia-related causes. Dementia-related death was ascertained according to the Norwegian Cause of Death Registry. Cox regression was used to assess the relationship between random glucose levels (nonfasting) in individuals without and with diabetes mellitus and dementia-related death. Education, smoking, cardiovascular disease, body mass index, cholesterol, blood pressure, and physical activity were adjusted for. Individuals without diabetes mellitus at midlife with glucose levels between 6.5 and 11.0 mmol/L had a significantly greater risk of dementia-related death than those with levels less than 5.1 mmol/L (hazard ratio=1.32, 95% confidence interval=1.04-1.67) in a fully adjusted model. A dose-response relationship (P=.02) was observed. No significant association between high glucose levels in individuals aged 65 to 80 and dementia-related death was detected. High random glucose levels measured in middle-aged but not older age persons without known diabetes mellitus were associated with greater risk of dementia-related death up to four decades later. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study.

PubMed

Long, Georgina V; Atkinson, Victoria; Lo, Serigne; Sandhu, Shahneen; Guminski, Alexander D; Brown, Michael P; Wilmott, James S; Edwards, Jarem; Gonzalez, Maria; Scolyer, Richard A; Menzies, Alexander M; McArthur, Grant A

2018-05-01

Nivolumab monotherapy and combination nivolumab plus ipilimumab increase proportions of patients achieving a response and survival versus ipilimumab in patients with metastatic melanoma; however, efficacy in active brain metastases is unknown. We aimed to establish the efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with active melanoma brain metastases. This multicentre open-label randomised phase 2 trial was done at four sites in Australia, in three cohorts of immunotherapy-naive patients aged 18 years or older with melanoma brain metastases. Patients with asymptomatic brain metastases with no previous local brain therapy were randomly assigned using the biased coin minimisation method, stratified by site, in a 30:24 ratio (after a safety run-in of six patients) to cohort A (nivolumab plus ipilimumab) or cohort B (nivolumab). Patients with brain metastases in whom local therapy had failed, or who had neurological symptoms, or leptomeningeal disease were enrolled in non-randomised cohort C (nivolumab). Patients in cohort A received intravenous nivolumab 1 mg/kg combined with ipilimumab 3 mg/kg every 3 weeks for four doses, then nivolumab 3 mg/kg every 2 weeks; patients in cohort B or cohort C received intravenous nivolumab 3 mg/kg every 2 weeks. The primary endpoint was intracranial response from week 12. Primary and safety analyses were done on an intention-to-treat basis in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, number NCT02374242, and is ongoing for the final survival analysis. Between Nov 4, 2014, and April 21, 2017, 79 patients were enrolled; 36 in cohort A, 27 in cohort B, and 16 in cohort C. One patient in cohort A and two in cohort B were found to be ineligible and excluded from the study before receiving the study drug. At the data cutoff (Aug 28, 2017), with a median follow up of 17 months (IQR 8-25), intracranial responses were achieved by 16 (46%; 95% CI 29-63) of 35 patients in cohort A, five (20%; 7-41) of 25 in cohort B, and one (6%; 0-30) of 16 in cohort C. Intracranial complete responses occurred in six (17%) patients in cohort A, three (12%) in cohort B, and none in cohort C. Treatment-related adverse events occurred in 34 (97%) of 35 patients in cohort A, 17 (68%) of 25 in cohort B, and eight (50%) of 16 in cohort C. Grade 3 or 4 treatment-related adverse events occurred in 19 (54%) patients in cohort A, four (16%) in cohort B, and two (13%) in cohort C. No treatment-related deaths occurred. Nivolumab combined with ipilimumab and nivolumab monotherapy are active in melanoma brain metastases. A high proportion of patients achieved an intracranial response with the combination. Thus, nivolumab combined with ipilimumab should be considered as a first-line therapy for patients with asymptomatic untreated brain metastases. Melanoma Institute Australia and Bristol-Myers Squibb. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genetic Obesity and the Risk of Atrial Fibrillation – Causal Estimates from Mendelian Randomization

PubMed Central

Chatterjee, Neal A.; Arking, Dan E.; Ellinor, Patrick T.; Heeringa, Jan; Lin, Honghuang; Lubitz, Steven A.; Soliman, Elsayed Z.; Verweij, Niek; Alonso, Alvaro; Benjamin, Emelia J.; Gudnason, Vilmundur; Stricker, Bruno H. C.; Van Der Harst, Pim; Chasman, Daniel I.; Albert, Christine M.

2017-01-01

Background Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding, reverse causation, and bias. The primary objective of this study was to evaluate the causal association between BMI and AF using genetic predictors of BMI. Methods We identified 51 646 individuals of European ancestry without AF at baseline from seven prospective population-based cohorts initiated between 1987 and 2002 in the United States, Iceland, and the Netherlands with incident AF ascertained between 1987 and 2012. Cohort-specific mean follow-up ranged 7.4 to 19.2 years, over which period there were a total of 4178 cases of incident AF. We performed a Mendelian randomization with instrumental variable analysis to estimate a cohort-specific causal hazard ratio for the association between BMI and AF. Two genetic instruments for BMI were utilized: FTO genotype (rs1558902) and a BMI gene score comprised of 39 single nucleotide polymorphisms identified by genome-wide association studies to be associated with BMI. Cohort-specific estimates were combined by random-effects, inverse variance weighted meta-analysis. Results In age- and sex-adjusted meta-analysis, both genetic instruments were significantly associated with BMI (FTO: 0.43 [95% CI: 0.32 – 0.54] kg/m2 per A-allele, p<0.001); BMI gene score: 1.05 [95% CI: 0.90-1.20] kg/m2 per 1 unit increase, p<0.001) and incident AF (FTO – HR: 1.07 [1.02-1.11] per A-allele, p=0.004; BMI gene score – HR: 1.11 [1.05-1.18] per 1-unit increase, p<0.001). Age- and sex-adjusted instrumental variable estimates for the causal association between BMI and incident AF were HR 1.15 [1.04-1.26] per kg/m2, p=0.005 (FTO) and 1.11 [1.05-1.17] per kg/m2, p<0.001 (BMI gene score). Both of these estimates were consistent with the meta-analyzed estimate between observed BMI and AF (age- and sex-adjusted HR 1.05 [1.04-1.06] per kg/m2, p<0.001). Multivariable adjustment did not significantly change findings. Conclusions Our data are consistent with a causal relationship between BMI and incident AF. These data support the possibility that public health initiatives targeting primordial prevention of obesity may reduce the incidence of AF. PMID:27974350

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

Mosaic stunting in bareroot Pinus banksiana seedlings is unrelated to colonization by mycorrhizal fungi

Treesearch

Lynette R. Potvin; Martin F. Jurgensen; R. Kasten Dumroese; Dana L. Richter; Deborah S. Page-Dumroese

2014-01-01

Mosaic stunting, the occurrence of random patches of chlorotic seedlings with reduced shoot and diameter growth amidst more robust cohorts within bareroot nurseries, is classically associated with poor colonization by mycorrhizal fungi. We examined possible relationships among soil fertility, mycorrhizas, and random patches of mosaic stunting in bareroot Pinus...

Cohort differences in dementia recognition and treatment indicators among assisted living residents in Maryland: did a change in the resident assessment tool make a difference?

PubMed

Samus, Quincy M; Vavilikolanu, Amrita; Mayer, Lawrence; McNabney, Matthew; Brandt, Jason; Lyketsos, Constantine G; Rosenblatt, Adam

2013-12-01

There is a lack of empirical evidence about the impact of regulations on dementia care quality in assisted living (AL). We examined cohort differences in dementia recognition and treatment indicators between two cohorts of AL residents with dementia, evaluated prior to and following a dementia-related policy modification to more adequately assess memory and behavioral problems. Cross-sectional comparison of two AL resident cohorts was done (Cohort 1 [evaluated 2001-2003] and Cohort 2 [evaluated 2004-2006]) from the Maryland Assisted Living studies. Initial in-person evaluations of residents with dementia (n = 248) were performed from a random sample of 28 AL facilities in Maryland (physician examination, clinical characteristics, and staff and family recognition of dementia included). Adequacy of dementia workup and treatment was rated by an expert consensus panel. Staff recognition of dementia was better in Cohort 1 than in Cohort 2 (77% vs. 63%, p = 0.011), with no significant differences in family recognition (86% vs. 85%, p = 0.680), or complete treatment ratings (52% vs. 64%, p = 0.060). In adjusted logistic regression, cognitive impairment and neuropsychiatric symptoms correlated with staff recognition; and cognitive impairment correlated with family recognition. Increased age and cognitive impairment reduced odds of having a complete dementia workup. Odds of having complete dementia treatment was reduced by age and having more depressive symptoms. Cohort was not predictive of dementia recognition or treatment indicators in adjusted models. We noted few cohort differences in dementia care indicators after accounting for covariates, and concluded that rates of dementia recognition and treatment did not appear to change much organically following the policy modifications.

Impact of frequent cerebrospinal fluid sampling on Aβ levels: systematic approach to elucidate influencing factors.

PubMed

Van Broeck, Bianca; Timmers, Maarten; Ramael, Steven; Bogert, Jennifer; Shaw, Leslie M; Mercken, Marc; Slemmon, John; Van Nueten, Luc; Engelborghs, Sebastiaan; Streffer, Johannes Rolf

2016-05-19

Cerebrospinal fluid (CSF) amyloid-beta (Aβ) peptides are predictive biomarkers for Alzheimer's disease and are proposed as pharmacodynamic markers for amyloid-lowering therapies. However, frequent sampling results in fluctuating CSF Aβ levels that have a tendency to increase compared with baseline. The impact of sampling frequency, volume, catheterization procedure, and ibuprofen pretreatment on CSF Aβ levels using continuous sampling over 36 h was assessed. In this open-label biomarker study, healthy participants (n = 18; either sex, age 55-85 years) were randomized into one of three cohorts (n = 6/cohort; high-frequency sampling). In all cohorts except cohort 2 (sampling started 6 h post catheterization), sampling through lumbar catheterization started immediately post catheterization. Cohort 3 received ibuprofen (800 mg) before catheterization. Following interim data review, an additional cohort 4 (n = 6) with an optimized sampling scheme (low-frequency and lower volume) was included. CSF Aβ(1-37), Aβ(1-38), Aβ(1-40), and Aβ(1-42) levels were analyzed. Increases and fluctuations in mean CSF Aβ levels occurred in cohorts 1-3 at times of high-frequency sampling. Some outliers were observed (cohorts 2 and 3) with an extreme pronunciation of this effect. Cohort 4 demonstrated minimal fluctuation of CSF Aβ both on a group and an individual level. Intersubject variability in CSF Aβ profiles over time was observed in all cohorts. CSF Aβ level fluctuation upon catheterization primarily depends on the sampling frequency and volume, but not on the catheterization procedure or inflammatory reaction. An optimized low-frequency sampling protocol minimizes or eliminates fluctuation of CSF Aβ levels, which will improve the capability of accurately measuring the pharmacodynamic read-out for amyloid-lowering therapies. ClinicalTrials.gov NCT01436188 . Registered 15 September 2011.

The Netherlands Cohort Study−Meat Investigation Cohort; a population-based cohort over-represented with vegetarians, pescetarians and low meat consumers.

PubMed

Gilsing, Anne M J; Weijenberg, Matty P; Goldbohm, R Alexandra; Dagnelie, Pieter C; van den Brandt, Piet A; Schouten, Leo J

2013-11-29

Vegetarian diets have been associated with lower risk of chronic disease, but little is known about the health effects of low meat diets and the reliability of self-reported vegetarian status. We aimed to establish an analytical cohort over-represented with vegetarians, pescetarians and 1 day/week meat consumers, and to describe their lifestyle and dietary characteristics. In addition, we were able to compare self-reported vegetarians with vegetarians whose status has been confirmed by their response on the extensive food frequency questionnaire (FFQ). Embedded within the Netherlands Cohort Study (n = 120,852; including 1150 self-reported vegetarians), the NLCS-Meat Investigation Cohort (NLCS-MIC) was defined by combining all FFQ-confirmed-vegetarians (n = 702), pescetarians (n = 394), and 1 day/week meat consumers (n = 1,396) from the total cohort with a random sample of 2-5 days/week- and 6-7 days/week meat consumers (n = 2,965 and 5,648, respectively). Vegetarians, pescetarians, and 1 day/week meat consumers had more favorable dietary intakes (e.g., higher fiber/vegetables) and lifestyle characteristics (e.g. lower smoking rates) compared to regular meat consumers in both sexes. Vegetarians adhered to their diet longer than pescetarians and 1 day/week meat consumers. 75% of vegetarians with a prevalent cancer at baseline had changed to this diet after diagnosis. 50% of self-reported vegetarians reported meat or fish consumption on the FFQ. Although the misclassification that occurred in terms of diet and lifestyle when merely relying on self-reporting was relatively small, the impact on associations with disease risk remains to be studied. We established an analytical cohort over-represented with persons at the lower end of the meat consumption spectrum which should facilitate prospective studies of major cancers and causes of death using ≥20.3 years of follow-up.

Tinned Fruit Consumption and Mortality in Three Prospective Cohorts

PubMed Central

Aasheim, Erlend T.; Sharp, Stephen J.; Appleby, Paul N.; Shipley, Martin J.; Lentjes, Marleen A. H.; Khaw, Kay-Tee; Brunner, Eric; Key, Tim J.; Wareham, Nicholas J.

2015-01-01

Dietary recommendations to promote health include fresh, frozen and tinned fruit, but few studies have examined the health benefits of tinned fruit. We therefore studied the association between tinned fruit consumption and mortality. We followed up participants from three prospective cohorts in the United Kingdom: 22,421 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort (1993–2012), 52,625 participants from the EPIC-Oxford cohort (1993–2012), and 7440 participants from the Whitehall II cohort (1991–2012), all reporting no history of heart attack, stroke, or cancer when entering these studies. We estimated the association between frequency of tinned fruit consumption and all cause mortality (primary outcome measure) using Cox regression models within each cohort, and pooled hazard ratios across cohorts using random-effects meta-analysis. Tinned fruit consumption was assessed with validated food frequency questionnaires including specific questions about tinned fruit. During 1,305,330 person years of follow-up, 8857 deaths occurred. After adjustment for lifestyle factors and risk markers the pooled hazard ratios (95% confidence interval) of all cause mortality compared with the reference group of tinned fruit consumption less often than one serving per month were: 1.05 (0.99, 1.12) for one to three servings per month, 1.10 (1.03, 1.18) for one serving per week, and 1.13 (1.04, 1.23) for two or more servings per week. Analysis of cause-specific mortality showed that tinned fruit consumption was associated with mortality from cardiovascular causes and from non-cardiovascular, non-cancer causes. In a pooled analysis of three prospective cohorts from the United Kingdom self-reported tinned fruit consumption in the 1990s was weakly but positively associated with mortality during long-term follow-up. These findings raise questions about the evidence underlying dietary recommendations to promote tinned fruit consumption as part of a healthy diet. PMID:25714554

CONSUMPTION OF ANIMAL FOODS AND ENDOMETRIAL CANCER RISK: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS

PubMed Central

Bandera, Elisa V.; Kushi, Lawrence H.; Moore, Dirk F.; Gifkins, Dina M.; McCullough, Marjorie L.

2008-01-01

This paper summarizes and quantifies the current evidence relating dietary intake of animal products and endometrial cancer. Literature searches were conducted to identify peer-reviewed manuscripts published up to December 2006. Twenty-two manuscripts from three cohort studies and 16 case-control studies were identified. One of these cohort studies evaluated only fried meat and another only milk consumption; they were not included in our meta-analyses. The third cohort study identified did not present exposure levels and could not be included in dose-response meta-analysis. This cohort study did not show an association with meat or red meat consumption. Random-effects dose-response summary estimates for case-control studies evaluating these foods were 1.26 (95% CI: 1.03–1.54) per 100 g/day of total meat, 1.51 (95% CI: 1.19–1.93) per 100 g/day of red meat, 1.03 (95% CI: 0.32–3.28) per 100 g/day of poultry, 1.04 (95% CI: 0.55–1.98) per 100 g/day of fish, and 0.97 (95% CI: 0.93–1.01) per serving of dairy. Our meta-analysis, based on case-control data, suggests that meat consumption, particularly red meat, increases endometrial cancer risk. The current literature does not support an association with dairy products, while the evidence is inconsistent for poultry, fish, and eggs. More studies, particularly prospective studies, are needed. PMID:17638104

A randomized trial of levonorgestrel intrauterine system insertion 6 to 48 h compared to 6 weeks after vaginal delivery; lessons learned.

PubMed

Stuart, Gretchen S; Lesko, Catherine R; Stuebe, Alison M; Bryant, Amy G; Levi, Erika E; Danvers, Antoinette I

2015-04-01

The objective of this randomized trial was to compare breastfeeding among women who received a levonorgestrel-releasing intrauterine system within 6-48 h (early) or 4-6 weeks (standard) after an uncomplicated vaginal birth. Analysis groups of 86 women in each arm were needed to demonstrate a 20% difference in any breastfeeding. Thirty-five women were randomized to the early (N=17) and standard (N=18) arms. The combination of unsuccessful placement (2/17; 12%), expulsions (7/17; 41%) and removals (3/17; 18%) reached 71% (12/17) in the early arm, so the study was stopped. In our small study cohort, levonorgestrel-releasing intrauterine system insertion between 6 and 48 h after vaginal birth was associated with a high rate of expulsion or removal soon after insertion. Copyright © 2015 Elsevier Inc. All rights reserved.

OpT2mise: a randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes-research design and methods.

PubMed

Aronson, Ronnie; Cohen, Ohad; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; de Portu, Simona; Lee, Scott; Reznik, Yves

2014-07-01

In insulin-requiring type 2 diabetes patients, current insulin therapy approaches such as basal-alone or basal-bolus multiple daily injections (MDI) have not consistently provided achievement of optimal glycemic control. Previous studies have suggested a potential benefit of continuous subcutaneous insulin infusion (CSII) in these patients. The OpT2mise study is a multicenter, randomized, trial comparing CSII with MDI in a large cohort of subjects with evidence of persistent hyperglycemia despite previous MDI therapy. Subjects were enrolled into a run-in period for optimization of their MDI insulin regimen. Subjects showing persistent hyperglycemia (glycated hemoglobin [HbA1c] ≥8% and ≤12%) were then randomly assigned to CSII or continuing an MDI regimen for a 6-month phase followed by a single crossover of the MDI arm, switching to CSII. The primary end point is the between-group difference in mean change in HbA1c from baseline to 6 months. Secondary end points include change in mean 24-h glucose values, area under the curve and time spent in hypoglycemia and hyperglycemia, measures of glycemic excursions, change in postprandial hyperglycemia, and evaluation of treatment satisfaction. Safety end points include hypoglycemia, hospital admissions, and emergency room visits. When subject enrollment was completed in May 2013, 495 subjects had been enrolled in the study. The study completion for the primary end point is expected in January 2014. OpT2mise will represent the largest studied homogeneous cohort of type 2 diabetes patients with persistent hyperglycemia despite optimized MDI therapy. OpT2mise will help define the role of CSII in insulin intensification and define its safety, rate of hypoglycemia, patient adherence, and patient satisfaction.

A nationwide population-based cohort study to identify the correlation between heart failure and the subsequent risk of herpes zoster.

PubMed

Wu, Ping-Hsun; Lin, Yi-Ting; Lin, Chun-Yi; Huang, Ming-Yii; Chang, Wei-Chiao; Chang, Wei-Pin

2015-01-16

The association between heart failure (HF) and herpes zoster has rarely been studied. We investigated the hypothesis that HF may increase the risk of herpes zoster in Taiwan using a nationwide Taiwanese population-based claims database. Our study cohort consisted of patients who received a diagnosis of HF in 2001 ~ 2009 (N = 4785). For a comparison cohort, three age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 14,355). All subjects were tracked for 1 year from the date of cohort entry to identify whether or not they had developed herpes zoster. Cox proportional-hazard regressions were performed to evaluate 1-year herpes zoster-free survival rates. The main finding of this study was that patients with HF seemed to be at an increased risk of developing herpes zoster. Of the total patients, 211 patients developed herpes zoster during the 1-year follow-up period, among whom 83 were HF patients and 128 were in the comparison cohort. The adjusted hazard ratio (AHR) of herpes zoster in patients with HF was higher (AHR: 2.07; 95% confidence interval (CI): 1.54 ~ 2.78; p < 0.001) than that of the controls during the 1-year follow-up. Our study also investigated whether HF is a gender-dependent risk factor for herpes zoster. We found that male patients with HF had an increased risk of developing herpes zoster (AHR: 2.30 95% CI: 1.51 ~ 3.50; p < 0.001). The findings of our population-based study suggest that patients with HF may have an increased risk of herpes zoster. These health associations should be taken into consideration, and further studies should focused on the cost-effectiveness of the herpes zoster vaccine should be designed for HF patients.

Study designs for determining and comparing sensitivities of disease screening tests.

PubMed

Prorok, Philip C; Kramer, Barnett S; Miller, Anthony B

2015-12-01

To investigate the capability of various study designs to determine the sensitivity of a disease screening test. Quantities that can be calculated from these designs were derived and examined for their relationship to true sensitivity (the ability to detect unrecognized disease that would surface clinically in the absence of screening) and overdiagnosis. To examine the sensitivity of one test, the single cohort design, in which all participants receive the test, is particularly weak, providing only an upper bound on the true sensitivity, and yields no information about overdiagnosis. A randomized design, with one control arm and participants tested in the other, that includes sufficient post-screening follow-up, allows calculation of bounds on, and an approximation to, true sensitivity and also determination of overdiagnosis. Without follow-up, bounds on the true sensitivity can be calculated. To compare two tests, the single cohort paired design in which all participants receive both tests is precarious. The three arm randomized design with post screening follow-up is preferred, yielding an approximation to the true sensitivity, bounds on the true sensitivity, and the extent of overdiagnosis of each test. Without post screening follow-up, bounds on the true sensitivities can be calculated. When an unscreened control arm is not possible, the two-arm randomized design is recommended. Individual test sensitivities cannot be determined, but with sufficient post-screening follow-up, an order relationship can be established, as can the difference in overdiagnosis between the two tests. © The Author(s) 2015.

Efficacy and safety of intravenous belimumab in Japanese patients with systemic lupus erythematosus: a subgroup analysis of a Phase 3 randomized placebo-controlled trial.

PubMed

Tanaka, Yoshiya; Bass, Damon; Chu, Myron; Egginton, Sally; Ji, Beulah; Struemper, Herbert; Roth, David

2018-05-24

To assess the efficacy and safety of intravenous belimumab plus standard systemic lupus erythematosus (SLE) therapy (SoC) in Japanese patients with SLE. A Phase 3, multicenter, double-blind, placebo-controlled, 52-week study (BEL 113750; NCT01345253) in patients with SLE, randomized 2:1 to belimumab 10 mg/kg plus SoC or placebo plus SoC to Week 48. Sixty of 707 randomized patients were enrolled from study centers in Japan (belimumab, n = 39; placebo, n = 21). In this cohort, more patients achieved SLE Responder Index 4 response at Week 52 in the belimumab group compared with placebo (46.2% [18/39] vs 25.0% [5/20]; odds ratio, 2.57 [95% confidence interval: 0.78, 8.47]; p = 0.1204). Fewer patients receiving belimumab experienced a severe flare through Week 52, with longer median time to flare compared with placebo. More patients with baseline prednisone dose >7.5 mg/day receiving belimumab had a dose reduction of ≥25% from baseline to ≤7.5 mg/day during Weeks 40 to 52, compared with placebo. No new safety issues were identified within the Japanese cohort. In Japanese patients with SLE, belimumab improved disease activity, with efficacy and safety results similar and consistent to the pivotal Phase 3 trials, suggesting that belimumab is a potential treatment option in this population.

Random placenta margin incision for control hemorrhage during cesarean delivery complicated by complete placenta previa: a prospective cohort study.

PubMed

Fan, Dazhi; Wu, Shuzhen; Ye, Shaoxin; Wang, Wen; Wang, Lijuan; Fu, Yao; Zeng, Meng; Liu, Yan; Guo, Xiaoling; Liu, Zhengping

2018-04-03

Complete placenta previa (CPP) is one of the most problematic types of abnormal placenta, which is further complicated by placenta accreta or percreta that can unexpectedly lead to catastrophic blood loss, infection, multiple complications, emergency hysterectomy, and even death. The present study aimed to assess the efficacy of random placenta margin incision in controlling intraoperative and total blood loss during cesarean section for CPP women. A prospective cohort study, including a total of 100 consecutive pregnant women with CPP, was performed at a tertiary university-affiliated medical center between March 2016 and July 2017. All of them underwent random placenta margin incision, and intraoperative and total blood loss were analyzed. Through antenatal diagnosis using color Doppler, women were further divided into abnormally invasive placenta (AIP) and non-AIP groups, and anterior and posterior placenta groups. The protocol was registered with the Clinical Trial Registry under registration number NCT02695069. Mean maternal age and gestational age at delivery were 32.26 ± 5.03 years old and 36.21 ± 2.07 weeks, respectively. Total duration of the surgical procedure time was 52.50 (42.43-64.00) min. Median estimated intraoperation blood loss was 746.43 (544.44-1092.86) ml. Total blood loss was 875.00 (604.50-1196.67) ml, and 38 (38.0%) had post-partum hemorrhage. The change from baseline in the median hemoglobin level was -0.33 (6.00-13.20). No women underwent hysterectomy due to massive hemorrhage during the study period. No women had an intraoperative urinary bladder injury, postoperative wound infection, and required relaparotomy, owing to intra-abdominal bleeding. The median hospitalization time was 5.41 (4.18-7.58) d. The random placenta margin incision may be a potentially valuable surgical procedure to control the volumes of intraoperative and postoperative blood loss and reduce the incidence of postpartum hemorrhage among women with complete placenta previa.

Effect of rater training on reliability and accuracy of mini-CEX scores: a randomized, controlled trial.

PubMed

Cook, David A; Dupras, Denise M; Beckman, Thomas J; Thomas, Kris G; Pankratz, V Shane

2009-01-01

Mini-CEX scores assess resident competence. Rater training might improve mini-CEX score interrater reliability, but evidence is lacking. Evaluate a rater training workshop using interrater reliability and accuracy. Randomized trial (immediate versus delayed workshop) and single-group pre/post study (randomized groups combined). Academic medical center. Fifty-two internal medicine clinic preceptors (31 randomized and 21 additional workshop attendees). The workshop included rater error training, performance dimension training, behavioral observation training, and frame of reference training using lecture, video, and facilitated discussion. Delayed group received no intervention until after posttest. Mini-CEX ratings at baseline (just before workshop for workshop group), and four weeks later using videotaped resident-patient encounters; mini-CEX ratings of live resident-patient encounters one year preceding and one year following the workshop; rater confidence using mini-CEX. Among 31 randomized participants, interrater reliabilities in the delayed group (baseline intraclass correlation coefficient [ICC] 0.43, follow-up 0.53) and workshop group (baseline 0.40, follow-up 0.43) were not significantly different (p = 0.19). Mean ratings were similar at baseline (delayed 4.9 [95% confidence interval 4.6-5.2], workshop 4.8 [4.5-5.1]) and follow-up (delayed 5.4 [5.0-5.7], workshop 5.3 [5.0-5.6]; p = 0.88 for interaction). For the entire cohort, rater confidence (1 = not confident, 6 = very confident) improved from mean (SD) 3.8 (1.4) to 4.4 (1.0), p = 0.018. Interrater reliability for ratings of live encounters (entire cohort) was higher after the workshop (ICC 0.34) than before (ICC 0.18) but the standard error of measurement was similar for both periods. Rater training did not improve interrater reliability or accuracy of mini-CEX scores. clinicaltrials.gov identifier NCT00667940

Tea consumption may decrease the risk of osteoporosis: an updated meta-analysis of observational studies.

PubMed

Guo, Ming; Qu, Hua; Xu, Lin; Shi, Da-Zhuo

2017-06-01

Several epidemiological investigations have evaluated the correlation between tea consumption and risk of osteoporosis, but the results are inconsistent. Therefore, we conducted an updated meta-analysis of observational studies to assess this association. We searched for all relevant studies including cohort, cross-sectional, and case-control studies published from database inception to July 15, 2016, using MEDLINE EMBASE, and Cochrane Library. Polled odds ratios (ORs) were calculated using the random-effect model. Fourteen articles (16 studies) that examined 138523 patients were included in this meta-analysis. Seven studies concerning bone mineral density (BMD) showed an increase in BMD with tea consumption, including 4 cross-sectional studies (OR, 0.04, 95% confidence interval [CI], 0.01-0.08) and 3 cohort studies (OR, 0.01; 95% CI, 0.01-0.01). The remaining 9 studies concerning fracture, including 6 case-control studies and 3 cohort studies, showed no association between tea consumption and osteoporotic fracture (OR, 0.86; 95% CI, 0.74-1.01). This updated meta-analysis demonstrates that tea consumption could increase BMD, but the association with osteoporotic fracture requires further investigation. Together, the results highlight the need for future, high-quality-designed clinical trials on tea consumption and osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis.

PubMed

Soon, Ing Shian; Molodecky, Natalie A; Rabi, Doreen M; Ghali, William A; Barkema, Herman W; Kaplan, Gilaad G

2012-05-24

The objective of this study was to conduct a systematic review with meta-analysis of studies assessing the association between living in an urban environment and the development of the Crohn's disease (CD) or ulcerative colitis (UC). A systematic literature search of MEDLINE (1950-Oct. 2009) and EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the relationship between urban environment and IBD. Cohort and case-control studies were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 % confidence intervals (CIs), respectively. Stratified and sensitivity analyses were performed to explore heterogeneity between studies and assess effects of study quality. The search strategy retrieved 6940 unique citations and 40 studies were selected for inclusion. Of these, 25 investigated the relationship between urban environment and UC and 30 investigated this relationship with CD. Included in our analysis were 7 case-control UC studies, 9 case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on a random effects model, the pooled IRRs for urban compared to rural environment for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively. These associations persisted across multiple stratified and sensitivity analyses exploring clinical and study quality factors. Heterogeneity was observed in the cohort studies for both UC and CD, whereas statistically significant heterogeneity was not observed for the case-control studies. A positive association between urban environment and both CD and UC was found. Heterogeneity may be explained by differences in study design and quality factors.

A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis

PubMed Central

Chao, Ming; Wu, Hao; Jin, Kai; Li, Bin; Wu, Jianjun; Zhang, Guangqiang; Yang, Gong; Hu, Xun

2016-01-01

Study design: Previous works suggested that neutralizing intratumoral lactic acidosis combined with glucose deprivation may deliver an effective approach to control tumor. We did a pilot clinical investigation, including a nonrandomized (57 patients with large HCC) and a randomized controlled (20 patients with large HCC) studies. Methods: The patients were treated with transarterial chemoembolization (TACE) with or without bicarbonate local infusion into tumor. Results: In the nonrandomized controlled study, geometric mean of viable tumor residues (VTR) in TACE with bicarbonate was 6.4-fold lower than that in TACE without bicarbonate (7.1% [95% CI: 4.6%–10.9%] vs 45.6% [28.9%–72.0%]; p<0.0001). This difference was recapitulated by a subsequent randomized controlled study. TACE combined with bicarbonate yielded a 100% objective response rate (ORR), whereas the ORR treated with TACE alone was 44.4% (nonrandomized) and 63.6% (randomized). The survival data suggested that bicarbonate may bring survival benefit. Conclusion: Bicarbonate markedly enhances the anticancer activity of TACE. Clinical trail registration: ChiCTR-IOR-14005319. DOI: http://dx.doi.org/10.7554/eLife.15691.001 PMID:27481188

Associations of Glycemic Index and Load With Coronary Heart Disease Events: A Systematic Review and Meta-Analysis of Prospective Cohorts

PubMed Central

Mirrahimi, Arash; de Souza, Russell J.; Chiavaroli, Laura; Sievenpiper, John L.; Beyene, Joseph; Hanley, Anthony J.; Augustin, Livia S. A.; Kendall, Cyril W. C.; Jenkins, David J. A.

2012-01-01

Background Glycemic index (GI) and glycemic load (GL) have been associated with coronary heart disease (CHD) risk in some but not all cohort studies. We therefore assessed the association of GI and GL with CHD risk in prospective cohorts. Methods and Results We searched MEDLINE, EMBASE, and CINAHL (through April 5, 2012) and identified all prospective cohorts assessing associations of GI and GL with incidence of CHD. Meta-analysis of observational studies in epidemiology (MOOSE) methodologies were used. Relative measures of risk, comparing the group with the highest exposure (mean GI of cohorts=84.4 GI units, range 79.9 to 91; mean GL of cohorts=224.8, range 166 to 270) to the reference group (mean GI=72.3 GI units, range 68.1 to 77; mean GL=135.4, range 83 to 176), were pooled using random-effects models, expressed as relative risk (RR) with heterogeneity assessed by χ2 and quantified by I2. Subgroups included sex and duration of follow-up. Ten studies (n=240 936) were eligible. Pooled analyses showed an increase in CHD risk for the highest GI quantile compared with the lowest, with RR=1.11 (95% confidence interval [CI] 0.99 to 1.24) and for GL, RR=1.27 (95% CI 1.09 to 1.49), both with evidence of heterogeneity (I2>42%, P<0.07). Subgroup analyses revealed only a significant modification by sex, with the female cohorts showing significance for GI RR=1.26 (95% CI 1.12 to 1.41) and for GL RR=1.55 (95% CI 1.18 to 2.03). Conclusions High GI and GL diets were significantly associated with CHD events in women but not in men. Further studies are required to determine the relationship between GI and GL with CHD in men. PMID:23316283

Effects of socioeconomic status on physical and mental health of hemodialysis patients in Japan: differences by age, period, and cohort

PubMed Central

Sugisawa, Hidehiro; Shimizu, Yumiko; Kumagai, Tamaki; Sugisaki, Hiroaki; Ohira, Seiji; Shinoda, Toshio

2016-01-01

Study purpose Whether or not socioeconomic status (SES)-related differences in the health of hemodialysis patients differ by age, period, and birth cohort remains unclear. We examined whether SES-related gaps in physical and mental health change with age, period, and birth cohort for hemodialysis patients. Methods Data were obtained from repeated cross-sectional surveys conducted in 1996, 2001, 2006, and 2011, with members of a national patients’ association as participants. We used raking adjustment to create a database which had similar characteristics to the total sample of dialysis patients in Japan. SES was assessed using family size-adjusted income levels. We divided patients into three groups based on their income levels: below the first quartile, over the second quartile and under the third quartile, and over the fourth quartile. We used the number of dialysis complications as a physical health indicator and depressive symptoms as a mental health indicator. We used a cross-classified random-effects model that estimated fixed effects of age categories and period as level-1 factors, and random effects of birth cohort as level-2 factors. Results Relative risk of dialysis complications in respondents below the first quartile compared with ones over the fourth quartile was reduced in age categories >60 years. Mean differences in depressive symptoms between respondents below the first quartile and ones over the fourth quartile peaked in the 50- to 59-year-old age group, and were reduced in age groups >60 years. In addition, mean differences varied across periods, widening from 1996 to 2006. There were no significant birth cohort effects on income differences for dialysis complications or depressive symptoms. Conclusion The number of dialysis complications and depressive symptoms in dialysis patients were affected by income differences, and the degree of these differences changed with age category and period. PMID:27471405

Prevalence, clinical features and risk assessment of pre-diabetes in Spain: the prospective Mollerussa cohort study

PubMed Central

Vilanova, María Belén; Falguera, Mireia; Marsal, Josep Ramon; Rubinat, Esther; Alcubierre, Núria; Catelblanco, Esmeralda; Granado-Casas, Minerva; Miró, Neus; Molló, Àngels; Mata-Cases, Manel; Franch-Nadal, Josep; Mauricio, Didac

2017-01-01

Purpose The Mollerussa prospective cohort was created to study pre-diabetes in a population-based sample from the primary care setting in the semirural area of Pla d’Urgell in Catalonia (Spain). The aims of the study were to assess the prevalence of pre-diabetes in our population, the likelihood to develop overt diabetes over time and to identify risk factors associated with the progression of the condition. Participants The cohort includes 594 subjects randomly selected between March 2011 and July 2014 from our primary care population, who were older than 25 years, consented to participate and did not have a recorded diagnosis of diabetes. Findings to date At baseline, we performed a clinical interview to collect demographic, clinical and lifestyle (including a nutritional survey) characteristics; carotid ultrasound imaging to assess subclinical cardiovascular disease was also performed, and a blood sample was collected, with an overall <5% rate of missing data. An additional blood draw was performed 12 months after initial recruitment to reassess laboratory results in patients initially identified as having pre-diabetes, with an 89.6% retention rate. Several studies investigating various hypotheses are currently ongoing. Future plans All subjects recruited during the cohort creation will be followed long-term through annual extraction of data from health records stored in the electronic Clinical station in Primary Care database. The Mollerussa cohort will thus be a sound population-based sample for multiple future research projects to generate insights into the epidemiology and natural history of pre-diabetes in Spain. PMID:28606902

Cohort profile: Ho Chi Minh City Youth Cohort--changes in diet, physical activity, sedentary behaviour and relationship with overweight/obesity in adolescents.

PubMed

Trang, Nguyen Hoang Hanh Doan; Hong, Tang Kim; Dibley, Michael John

2012-01-01

The Ho Chi Minh Youth cohort study aimed to assess the change in nutritional status; indicators of adiposity; diet; physical activity and sedentary behaviours; home, neighbourhood and school microenvironments and their complex relationships in adolescents in urban areas of Ho Chi Minh City. Prospective 5-year cohort. Systematic random sampling was used to select 18 schools in urban districts. Children were followed up over 5 years with an assessment in each year. Consent, from both adolescents and their parents, was required. At baseline, 759 students were recruited into the cohort, and of these students, 740 remained in the cohort for the first round, 712 for the second round, 630 for the third round and 585 for the last round of follow-up. Anthropometric measurements were taken using established guidelines. Six main groups of exposure factors including dietary intake and behaviours, physical activity and sedentary behaviours, family social and physical environment, school environment, socioeconomic status and parental characteristics were measured. Retention rate was high (77%). Within 5-year period, the prevalence of combined overweight and obesity using International Obesity Task Force cut-off values increased from 14.2% to 21.8%. Time spent on physical activity decreased significantly in the 5-year period from 87 to 50 min/day. Time spent on sedentary behaviours increased in the 5-year period from 512 to 600 min/day. The complete data analysis of this cohort study will allow a full exploration of the role of environmental and lifestyle behaviours on adolescent overweight and obesity and also identify the factors most strongly associated with excess weight gain and the appearance of overweight and obesity in different age groups of adolescents from this large city in Vietnam.

Increasing Kyphosis Predicts Worsening Mobility in Older Community-Dwelling Women: A Prospective Cohort Study

PubMed Central

Katzman, Wendy B.; Vittinghoff, Eric; Ensrud, Kris; Black, Dennis M.; Kado, Deborah M.

2013-01-01

OBJECTIVES To determine whether increasing kyphosis angle was independently associated with poorer mobility as measured according to the Timed Up and Go Test (TUG), after controlling for other established risk factors. DESIGN Prospective cohort study. SETTING Eleven clinical centers in the United States. PARTICIPANTS Two thousand seven hundred seventy-seven women aged 55 to 80 randomized to the placebo arms of the Fracture Intervention Trial, a randomized controlled trial of the effect of alendronate on risk for osteoporotic fractures. MEASUREMENTS The primary predictor was change in kyphosis angle, measured using the Debrunner Kyphometer; the outcome was change in mobility, measured as performance time on the TUG. Covariates were baseline age, kyphosis angle, body mass index (BMI), self-reported health status, grip strength, change in total hip bond mineral density (BMD), and number of vertebral fractures over a mean of 4.4 years. RESULTS Greater kyphosis angle predicted longer mobility performance times (P<.001), independent of other significant predictors of worsening mobility including age, baseline kyphosis, health status, grip strength, BMI, change in hip BMD, and new vertebral fractures. TUG performance times increased by 0.02 seconds (95% confidence interval (CI) =0.01–0.03) for every 5° increase in kyphosis angle, more than the increase in mobility time of 0.01 seconds (95% CI =0.005–0.03) over 1 year observed in this cohort. CONCLUSION Increasing kyphosis angle is independently associated with worsening mobility. Interventions are needed to prevent or reduce increasing kyphosis and mobility decline. PMID:21198460

Consumption of Yogurt and the Incident Risk of Cardiovascular Disease: A Meta-Analysis of Nine Cohort Studies.

PubMed

Wu, Lei; Sun, Dali

2017-03-22

Previous systematic reviews and meta-analyses have evaluated the association of dairy consumption and the risk of cardiovascular disease (CVD). However, the findings were inconsistent. No quantitative analysis has specifically assessed the effect of yogurt intake on the incident risk of CVD. We searched the PubMed and the Embase databases from inception to 10 January 2017. A generic inverse-variance method was used to pool the fully-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) with a random-effects model. A generalized least squares trend estimation model was used to calculate the specific slopes in the dose-response analysis. The present systematic review and meta-analysis identified nine prospective cohort articles involving a total of 291,236 participants. Compared with the lowest category, highest category of yogurt consumption was not significantly related with the incident risk of CVD, and the RR (95% CI) was 1.01 (0.95, 1.08) with an evidence of significant heterogeneity (I² = 52%). However, intake of ≥200 g/day yogurt was significantly associated with a lower risk of CVD in the subgroup analysis. There was a trend that a higher level of yogurt consumption was associated with a lower incident risk of CVD in the dose-response analysis. A daily dose of ≥200 g yogurt intake might be associated with a lower incident risk of CVD. Further cohort studies and randomized controlled trials are still demanded to establish and confirm the observed association in populations with different characteristics.

Consumption of Yogurt and the Incident Risk of Cardiovascular Disease: A Meta-Analysis of Nine Cohort Studies

PubMed Central

Wu, Lei; Sun, Dali

2017-01-01

Previous systematic reviews and meta-analyses have evaluated the association of dairy consumption and the risk of cardiovascular disease (CVD). However, the findings were inconsistent. No quantitative analysis has specifically assessed the effect of yogurt intake on the incident risk of CVD. We searched the PubMed and the Embase databases from inception to 10 January 2017. A generic inverse-variance method was used to pool the fully-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) with a random-effects model. A generalized least squares trend estimation model was used to calculate the specific slopes in the dose-response analysis. The present systematic review and meta-analysis identified nine prospective cohort articles involving a total of 291,236 participants. Compared with the lowest category, highest category of yogurt consumption was not significantly related with the incident risk of CVD, and the RR (95% CI) was 1.01 (0.95, 1.08) with an evidence of significant heterogeneity (I2 = 52%). However, intake of ≥200 g/day yogurt was significantly associated with a lower risk of CVD in the subgroup analysis. There was a trend that a higher level of yogurt consumption was associated with a lower incident risk of CVD in the dose-response analysis. A daily dose of ≥200 g yogurt intake might be associated with a lower incident risk of CVD. Further cohort studies and randomized controlled trials are still demanded to establish and confirm the observed association in populations with different characteristics. PMID:28327514

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study

PubMed Central

Kulich, M.; Řeřicha, V.; Řeřicha, R.; Shore, D.L.; Sandler, D.P.

2011-01-01

Objectives Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. Methods A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n = 1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Results Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73 – 1.04, n = 1020), 0.87 for all digestive cancers (95% CI 0.69 – 1.09, n = 561), 2.39 for gallbladder cancer (95% CI 0.52 – 10.98, n = 13), 0.79 for larynx cancer (95% CI 0.38 – 1.64, n = 62), 2.92 for malignant melanoma (95% CI 0.91 – 9.42, n = 23), 0.84 for bladder cancer (95% CI 0.43 – 1.65, n = 73), and 1.13 for kidney cancer (95% CI 0.62 – 2.04, n = 66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Conclusions Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. PMID:21256480

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study.

PubMed

Kulich, M; Reřicha, V; Reřicha, R; Shore, D L; Sandler, D P

2011-04-01

Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. Copyright © 2011 Elsevier Inc. All rights reserved.

Psychological consequences of child trafficking: An historical cohort study of trafficked children in contact with secondary mental health services

PubMed Central

Smith, Patrick; Shetty, Hitesh; Stahl, Daniel; Oram, Sian

2018-01-01

Background Child trafficking is the recruitment and movement of people aged younger than 18 for the purposes of exploitation. Research on the mental health of trafficked children is limited, and little is known about the use of mental health services by this group. This study aimed to investigate the mental health and service use characteristics of trafficked children in contact with mental health services in England. Methods & findings The study employed an historical cohort design. Electronic health records of over 250,000 patients were searched to identify trafficked children, and a matched cohort of non-trafficked children was randomly selected. Data were extracted on the socio-demographic and clinical characteristics, abuse history, and trafficking experiences of the trafficked children. Logistic and linear random effects regression models were fitted to compare trafficked and non-trafficked children on their clinical profiles and service use characteristics. Fifty-one trafficked children were identified, 78% were female. The most commonly recorded diagnoses for trafficked children were post-traumatic stress disorder (PTSD) (22%) and affective disorders (22%). Records documented a high prevalence of physical violence (53%) and sexual violence (49%) among trafficked children. Trafficked children had significantly longer duration of contact with mental health services compared to non-trafficked controls (b = 1.66, 95% CI 1.09–2.55, p<0.02). No significant differences were found, however, with regards to pathways into care, prevalence of compulsory psychiatric admission, length of inpatient stays, or changes in global functioning. Conclusions Child trafficking is associated with high levels of physical and sexual abuse and longer duration of contact with mental health services. Research is needed on most effective interventions to promote recovery for this vulnerable group. PMID:29518168

Psychological consequences of child trafficking: An historical cohort study of trafficked children in contact with secondary mental health services.

PubMed

Ottisova, Livia; Smith, Patrick; Shetty, Hitesh; Stahl, Daniel; Downs, Johnny; Oram, Sian

2018-01-01

Child trafficking is the recruitment and movement of people aged younger than 18 for the purposes of exploitation. Research on the mental health of trafficked children is limited, and little is known about the use of mental health services by this group. This study aimed to investigate the mental health and service use characteristics of trafficked children in contact with mental health services in England. The study employed an historical cohort design. Electronic health records of over 250,000 patients were searched to identify trafficked children, and a matched cohort of non-trafficked children was randomly selected. Data were extracted on the socio-demographic and clinical characteristics, abuse history, and trafficking experiences of the trafficked children. Logistic and linear random effects regression models were fitted to compare trafficked and non-trafficked children on their clinical profiles and service use characteristics. Fifty-one trafficked children were identified, 78% were female. The most commonly recorded diagnoses for trafficked children were post-traumatic stress disorder (PTSD) (22%) and affective disorders (22%). Records documented a high prevalence of physical violence (53%) and sexual violence (49%) among trafficked children. Trafficked children had significantly longer duration of contact with mental health services compared to non-trafficked controls (b = 1.66, 95% CI 1.09-2.55, p<0.02). No significant differences were found, however, with regards to pathways into care, prevalence of compulsory psychiatric admission, length of inpatient stays, or changes in global functioning. Child trafficking is associated with high levels of physical and sexual abuse and longer duration of contact with mental health services. Research is needed on most effective interventions to promote recovery for this vulnerable group.

Risk of Retinal Vein Occlusion in Patients With End-Stage Renal Disease: A 12-Year, Retrospective, Nationwide Cohort Study in South Korea.

PubMed

Lee, Kyung Sik; Nam, Ki Heon; Kim, Dong Wook; Kang, Eui Chun; Koh, Hyoung Jun

2018-01-01

The present study aimed to evaluate the risk of retinal vein occlusion (RVO) in Korean patients with end-stage renal disease (ESRD). In this retrospective, nationwide, propensity score-matched cohort study, subjects were randomly enrolled from the 12-year longitudinal Korean National Health Insurance Service-National Sample Cohort 2002-2013 database comprising 1 million subjects. The ESRD group comprised 988 patients newly diagnosed with ESRD from 2003 onward by washing out data from 2002. The comparison group comprised 4940 (5 for each patient with ESRD) randomly selected propensity score-matched individuals not diagnosed with ESRD. Each sampled patient was tracked until 2013 for RVO development. Multiple conditional Cox regression analysis was performed to compare the risk of RVO between the two groups. The mean follow-up period was 7.37 years. The incidence of RVO was 3.95% in the ESRD group and 2.17% in the comparison group (P = 0.001). ESRD was associated with greater risk of RVO development after adjustment for possible confounders (adjusted hazard ratio [HR], 2.122; 95% confidence interval [CI], 1.396-3.226; P = 0.0004). The 50- to 60-year (adjusted HR, 2.635; 95% CI, 1.100-6.313; P = 0.0297) and 60- to 70-year (adjusted HR, 2.544; 95% CI, 1.059-6.110; P = 0.0368) age groups exhibited higher risk of RVO compared with the <40-year age group. Hyperlipidemia (adjusted HR, 1.670; 95% CI, 1.176-2.371; P = 0.0042) and hypertension (adjusted HR, 1.896; 95% CI, 1.165-3.086; P = 0.01) were also associated with RVO. An association between ESRD and subsequent RVO development was found after adjustment for possible confounding factors.

Perceived job insecurity as a risk factor for incident coronary heart disease: systematic review and meta-analysis

PubMed Central

Nyberg, Solja T; Batty, G David; Jokela, Markus; Heikkilä, Katriina; Fransson, Eleonor I; Alfredsson, Lars; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Casini, Annalisa; Clays, Els; De Bacquer, Dirk; Dragano, Nico; Elovainio, Marko; Erbel, Raimund; Ferrie, Jane E; Hamer, Mark; Jöckel, Karl-Heinz; Kittel, France; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Lunau, Thorsten; Madsen, Ida E H; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pahkin, Krista; Pejtersen, Jan H; Pentti, Jaana; Rugulies, Reiner; Salo, Paula; Shipley, Martin J; Siegrist, Johannes; Steptoe, Andrew; Suominen, Sakari B; Theorell, Töres; Toppinen-Tanner, Salla; Väänänen, Ari; Vahtera, Jussi; Westerholm, Peter J M; Westerlund, Hugo; Slopen, Natalie; Kawachi, Ichiro; Singh-Manoux, Archana; Kivimäki, Mika

2013-01-01

Objective To determine the association between self reported job insecurity and incident coronary heart disease. Design A meta-analysis combining individual level data from a collaborative consortium and published studies identified by a systematic review. Data sources We obtained individual level data from 13 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. Four published prospective cohort studies were identified by searches of Medline (to August 2012) and Embase databases (to October 2012), supplemented by manual searches. Review methods Prospective cohort studies that reported risk estimates for clinically verified incident coronary heart disease by the level of self reported job insecurity. Two independent reviewers extracted published data. Summary estimates of association were obtained using random effects models. Results The literature search yielded four cohort studies. Together with 13 cohort studies with individual participant data, the meta-analysis comprised up to 174 438 participants with a mean follow-up of 9.7 years and 1892 incident cases of coronary heart disease. Age adjusted relative risk of high versus low job insecurity was 1.32 (95% confidence interval 1.09 to 1.59). The relative risk of job insecurity adjusted for sociodemographic and risk factors was 1.19 (1.00 to 1.42). There was no evidence of significant differences in this association by sex, age (<50 v ≥50 years), national unemployment rate, welfare regime, or job insecurity measure. Conclusions The modest association between perceived job insecurity and incident coronary heart disease is partly attributable to poorer socioeconomic circumstances and less favourable risk factor profiles among people with job insecurity. PMID:23929894

Risk of Parkinson's disease following zolpidem use: a retrospective, population-based cohort study.

PubMed

Huang, Hui-Chun; Tsai, Chon-Haw; Muo, Chih-Hsin; Lin, Kang-Hsu; Lu, Ming-Kuei; Sung, Fung-Chang; Kao, Chia-Hung

2015-01-01

To evaluate the influence of long-term zolpidem use on the incidence of developing Parkinson's disease. 2,961 subjects who used zolpidem for the first time longer than 3 months between 1998 and 2000 were identified in the National Health Insurance system of Taiwan. Subjects without a history of zolpidem use were randomly selected as a comparison cohort and frequency matched to zolpidem users based on age, sex, and index date. The diagnosis of Parkinson's disease was based on the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification. Its incidence until the end of 2009 was calculated and its hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models and Kaplan-Meier analysis. The overall incidence of Parkinson's disease was greater among zolpidem users than in the comparison cohort (HR = 1.88; 95% CI, 1.45-2.45). However, there was no difference in Parkinson's disease incidence between these 2 cohorts after 5 years of observation. The risk of Parkinson's disease increased with increasing zolpidem dose, with an HR of 0.70 for low-dose users (< 400 mg/y) and 2.94 for high-dose users (≥ 1,600 mg/y). The incidence of Parkinson's disease was greater in subjects using zolpidem only (HR = 2.35; 95% CI, 1.66-3.33) compared to those using benzodiazepines only (HR = 1.31; 95% CI, 0.91-1.90). By stratified analysis, zolpidem use with concurrent depression (HR = 4.79) increased the risk of Parkinson's disease compared to that of zolpidem users without concurrent depression. Zolpidem use might unmask preclinical Parkinson's disease, especially in patients with depression. However, large population-based, unbiased, randomized trials are warranted to confirm this finding. © Copyright 2015 Physicians Postgraduate Press, Inc.

Secular trends: a ten-year comparison of the amount and type of physical activity and inactivity of random samples of adolescents in the Czech Republic

PubMed Central

2011-01-01

Background An optimal level of physical activity (PA) in adolescence influences the level of PA in adulthood. Although PA declines with age have been demonstrated repeatedly, few studies have been carried out on secular trends. The present study assessed levels, types and secular trends of PA and sedentary behaviour of a sample of adolescents in the Czech Republic. Methods The study comprised two cross-sectional cohorts of adolescents ten years apart. The analysis compared data collected through a week-long monitoring of adolescents' PA in 1998-2000 and 2008-2010. Adolescents wore either Yamax SW-701 or Omron HJ-105 pedometer continuously for 7 days (at least 10 hours per day) excluding sleeping, hygiene and bathing. They also recorded their number of steps per day, the type and duration of PA and sedentary behaviour (in minutes) on record sheets. In total, 902 adolescents (410 boys; 492 girls) aged 14-18 were eligible for analysis. Results Overweight and obesity in Czech adolescents participating in this study increased from 5.5% (older cohort, 1998-2000) to 10.4% (younger cohort, 2008-2010). There were no inter-cohort significant changes in the total amount of sedentary behaviour in boys. However in girls, on weekdays, there was a significant increase in the total duration of sedentary behaviour of the younger cohort (2008-2010) compared with the older one (1998-2000). Studying and screen time (television and computer) were among the main sedentary behaviours in Czech adolescents. The types of sedentary behaviour also changed: watching TV (1998-2000) was replaced by time spent on computers (2008-2010). The Czech health-related criterion (achieving 11,000 steps per day) decreased only in boys from 68% (1998-2000) to 55% (2008-2010). Across both genders, 55%-75% of Czech adolescents met the health-related criterion of recommended steps per day, however less participants in the younger cohort (2008-2010) met this criterion than in the older cohort (1998-2000) ten years ago. Adolescents' PA levels for the monitored periods of 1998-2000 and 2008-2010 suggest a secular decrease in the weekly number of steps achieved by adolescent boys and girls. Conclusion In the younger cohort (2008-2010), every tenth adolescent was either overweight or obese; roughly twice the rate when compared to the older cohort (1998-2000). Sedentary behaviour seems relatively stable across the two cohorts as the increased time that the younger cohort (2008-2010) spent on computers is compensated with an equally decreased time spent watching TV or studying. Across both cohorts about half to three quarters of the adolescents met the health-related criterion for achieved number of steps. The findings show a secular decrease in PA amongst adolescents. The significant interaction effects (cohort × age; and cohort × gender) that this study found suggested that secular trends in PA differ by age and gender. PMID:21943194

Secular trends: a ten-year comparison of the amount and type of physical activity and inactivity of random samples of adolescents in the Czech Republic.

PubMed

Sigmundová, Dagmar; El Ansari, Walid; Sigmund, Erik; Frömel, Karel

2011-09-26

An optimal level of physical activity (PA) in adolescence influences the level of PA in adulthood. Although PA declines with age have been demonstrated repeatedly, few studies have been carried out on secular trends. The present study assessed levels, types and secular trends of PA and sedentary behaviour of a sample of adolescents in the Czech Republic. The study comprised two cross-sectional cohorts of adolescents ten years apart. The analysis compared data collected through a week-long monitoring of adolescents' PA in 1998-2000 and 2008-2010. Adolescents wore either Yamax SW-701 or Omron HJ-105 pedometer continuously for 7 days (at least 10 hours per day) excluding sleeping, hygiene and bathing. They also recorded their number of steps per day, the type and duration of PA and sedentary behaviour (in minutes) on record sheets. In total, 902 adolescents (410 boys; 492 girls) aged 14-18 were eligible for analysis. Overweight and obesity in Czech adolescents participating in this study increased from 5.5% (older cohort, 1998-2000) to 10.4% (younger cohort, 2008-2010). There were no inter-cohort significant changes in the total amount of sedentary behaviour in boys. However in girls, on weekdays, there was a significant increase in the total duration of sedentary behaviour of the younger cohort (2008-2010) compared with the older one (1998-2000). Studying and screen time (television and computer) were among the main sedentary behaviours in Czech adolescents. The types of sedentary behaviour also changed: watching TV (1998-2000) was replaced by time spent on computers (2008-2010).The Czech health-related criterion (achieving 11,000 steps per day) decreased only in boys from 68% (1998-2000) to 55% (2008-2010). Across both genders, 55%-75% of Czech adolescents met the health-related criterion of recommended steps per day, however less participants in the younger cohort (2008-2010) met this criterion than in the older cohort (1998-2000) ten years ago. Adolescents' PA levels for the monitored periods of 1998-2000 and 2008-2010 suggest a secular decrease in the weekly number of steps achieved by adolescent boys and girls. In the younger cohort (2008-2010), every tenth adolescent was either overweight or obese; roughly twice the rate when compared to the older cohort (1998-2000). Sedentary behaviour seems relatively stable across the two cohorts as the increased time that the younger cohort (2008-2010) spent on computers is compensated with an equally decreased time spent watching TV or studying. Across both cohorts about half to three quarters of the adolescents met the health-related criterion for achieved number of steps. The findings show a secular decrease in PA amongst adolescents. The significant interaction effects (cohort × age; and cohort × gender) that this study found suggested that secular trends in PA differ by age and gender.

Increased risk of stroke in contact dermatitis patients

PubMed Central

Chang, Wei-Lun; Hsu, Min-Hsien; Lin, Cheng-Li; Chan, Po-Chi; Chang, Ko-Shih; Lee, Ching-Hsiao; Hsu, Chung-Yi; Tsai, Min-Tein; Yeh, Chung-Hsin; Sung, Fung-Chang

2017-01-01

Abstract Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke. We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000–2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts. The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P < 0.01). The multivariable Cox method analyzed adjusted hazard ratios (aHRs) were 1.12 (95% confidence interval [CI], 1.05–1.19) for all stroke types and 1.12 (95% CI, 1.05–1.20) for ischemic stroke and 1.11 (95% CI, 0.94–1.30) for hemorrhagic stroke. The age-specific aHR of stroke for contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03–1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15–1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07–1.27) and 1.09 (95% CI, 1.00–1.18) for men and women, respectively. This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further. PMID:28272195

Random glucose is useful for individual prediction of type 2 diabetes: results of the Study of Health in Pomerania (SHIP).

PubMed

Kowall, Bernd; Rathmann, Wolfgang; Giani, Guido; Schipf, Sabine; Baumeister, Sebastian; Wallaschofski, Henri; Nauck, Matthias; Völzke, Henry

2013-04-01

Random glucose is widely used in routine clinical practice. We investigated whether this non-standardized glycemic measure is useful for individual diabetes prediction. The Study of Health in Pomerania (SHIP), a population-based cohort study in north-east Germany, included 3107 diabetes-free persons aged 31-81 years at baseline in 1997-2001. 2475 persons participated at 5-year follow-up and gave self-reports of incident diabetes. For the total sample and for subjects aged ≥50 years, statistical properties of prediction models with and without random glucose were compared. A basic model (including age, sex, diabetes of parents, hypertension and waist circumference) and a comprehensive model (additionally including various lifestyle variables and blood parameters, but not HbA1c) performed statistically significantly better after adding random glucose (e.g., the area under the receiver-operating curve (AROC) increased from 0.824 to 0.856 after adding random glucose to the comprehensive model in the total sample). Likewise, adding random glucose to prediction models which included HbA1c led to significant improvements of predictive ability (e.g., for subjects ≥50 years, AROC increased from 0.824 to 0.849 after adding random glucose to the comprehensive model+HbA1c). Random glucose is useful for individual diabetes prediction, and improves prediction models including HbA1c. Copyright © 2012 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Importance of anticoagulation and postablation silent cerebral lesions: Subanalyses of REVOLUTION and reMARQable studies.

PubMed

Grimaldi, Massimo; Swarup, Vijay; DeVille, Brian; Sussman, Jonathan; Jaïs, Pierre; Gaita, Fiorenzo; Duytschaever, Mattias; Ng, G Andre; Daoud, Emile; Lakkireddy, Dhanunjaya Dj; Horton, Rodney; Wickliffe, Andrew; Ellis, Christopher; Geller, Laszlo

2017-12-01

Silent cerebral lesions (SCLs) are a potential complication of left atrial radiofrequency ablation (RFA) procedures for paroxysmal atrial fibrillation (PAF). We aimed to compare the incidence of SCLs in patients treated with irrigated RFA multielectrode catheters (nMARQ ® Catheter group) and irrigated focal RFA catheters (NAVISTAR ® THERMOCOOL ® Catheter; TC group) after PAF ablation from subpopulation neurological assessment (SNA) cohorts of the REVOLUTION and reMARQable studies. Data from SNA cohorts in the prospective, nonrandomized REVOLUTION study (March 2011-September 2013) and the prospective, randomized, controlled reMARQable study (October 2013-November 2015) were included. The incidence of SCLs was assessed pre- and postablation using magnetic resonance imaging. Neurological deficits were assessed using the National Institutes of Health Stroke Scale, modified Rankin Scale, and Montreal Cognitive Assessment. A total of 37 patients from REVOLUTION and 76 patients from reMARQable were included in the SNA cohort of each study. In the REVOLUTION SNA cohort, the incidence of SCLs was 21.1% (4/19) in the nMARQ ® Catheter group and 5.9% (1/17) in the TC group. Findings from REVOLUTION helped inform the reMARQable study protocol's stringent anticoagulation regimen. SCL incidence was subsequently reduced in both groups (nMARQ ® Catheter, 7.9%; TC, 3.3%). No permanent neurological deficits were observed. Adherence to a stringent anticoagulation regimen prior to and during ablation procedures appears to be an important factor in minimizing the risk of SCL. © 2017 Wiley Periodicals, Inc.

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

PubMed

Balagopal, Ashwin; Asmuth, David M; Yang, Wei-Teng; Campbell, Thomas B; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R; Lalloo, Umesh G; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B; Semba, Richard D; Thomas, David L; Bollinger, Robert C; Gupta, Amita

2015-10-01

Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4 T-cell count <300 cells/mm; 9 countries) was conducted. A subcohort of 30 participants per country was randomly selected; additional cases were added from the main cohort. Cases [n = 236 (random subcohort 36; main cohort 200)] had clinical progression (incident WHO stage 3/4 event or death) within 96 weeks after cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4 T-cell count was 167 cells per cubic millimeter. In multivariate analysis, highest quartile C-reactive protein concentration [adjusted hazard ratio (aHR), 2.53; 95% confidence interval (CI): 1.02 to 6.28] and CD4 T-cell activation (aHR, 5.18; 95% CI: 1.09 to 24.47) were associated with primary outcomes, compared with lowest quartiles. sCD14 had a trend toward association with clinical failure (aHR, 2.24; 95% CI: 0.96 to 5.21). Measuring C-reactive protein and CD4 T-cell activation may identify patients with CD4 T-cell counts <300 cells per cubic millimeter at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.

Closing the Gap: Early Childhood Education. The Achievement Gap: Early Childhood Education. Info Brief. Number 45

ERIC Educational Resources Information Center

Nelson, Anne

2006-01-01

In popular culture, the age of 40 is sometimes considered "over the hill." This is decidedly not the case for the Perry Preschoolers--a cohort of low-income, predominantly African American children who 37 years ago were randomly assigned to attend a high-quality preschool program. The latest findings from the well-known longitudinal study of this…

Cohort profile: the QSkin Sun and Health Study.

PubMed

Olsen, Catherine M; Green, Adèle C; Neale, Rachel E; Webb, Penelope M; Cicero, Rebekah A; Jackman, Lea M; O'Brien, Suzanne M; Perry, Susan L; Ranieri, Barbara A; Whiteman, David C

2012-08-01

The QSkin Sun and Health Study comprises a cohort of 43 794 men and women aged 40-69 years randomly sampled from the population of Queensland, Australia in 2011. The cohort was established to study the development of skin cancer and melanoma in the population with the highest reported incidence of these diseases in the world. At baseline, besides demographic items and general medical history, information about standard pigmentary characteristics (including hair and eye colour, freckling tendency, tanning ability and propensity to sunburn), past and recent history of sun exposure and sunburns, sun protection behaviours, use of tanning beds and history of skin cancer was collected by self-completed questionnaire. Participants have given their consent for data linkage to the universal national health insurance scheme and for linkage to cancer registries and pathology databases, thus ensuring complete ascertainment of all future skin cancer and melanoma occurrences and medical treatments and other cancer events. Linkage to these registers will occur at predetermined intervals. Approval to access QSkin data can be obtained on application to the study investigators and submission of a formal research plan that has previous approval from the human research ethics committee of the applicant's institution.

Incinerator Pollution and Child Development in the Taiwan Birth Cohort Study

PubMed Central

Lung, For-Wey; Chiang, Tung-Liang; Lin, Shio-Jean; Shu, Bih-Ching

2013-01-01

This study aimed to investigate the direct and indirect effects of environmental pollutants on child development and parental concerns. It focused on the pathway relationships among the following factors: living within three kilometers of an incinerator, breastfeeding, place of residence, parental concerns about development, and parent-perceived child development. The Taiwan Birth Cohort Study (TBCS) dataset includes randomized community data on 21,248 children at six, 18, and 36 months of age. The Parental Concern Checklist and the Taiwan Birth Cohort Study-Developmental Instrument were used to measure parental concern and parent-perceived child development. Living within three kilometers of an incinerator increased the risk of children showing delayed development in the gross motor domain at six and 36 months. Although breastfeeding is a protective factor against uneven/delayed developmental disability (U/DDD), children living near an incinerator who were breastfed had an increased risk of U/DDD compared with those who did not live near incinerators. The presence of a local incinerator affected parent-perceived child development directly and indirectly through the mediating factor of breastfeeding. Further follow-up of these children to investigate the long-term effects of specific toxins on their development and later diagnostic categorization is necessary. PMID:23727903

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients.

PubMed

Leon, Martin B; Smith, Craig R; Mack, Michael J; Makkar, Raj R; Svensson, Lars G; Kodali, Susheel K; Thourani, Vinod H; Tuzcu, E Murat; Miller, D Craig; Herrmann, Howard C; Doshi, Darshan; Cohen, David J; Pichard, Augusto D; Kapadia, Samir; Dewey, Todd; Babaliaros, Vasilis; Szeto, Wilson Y; Williams, Mathew R; Kereiakes, Dean; Zajarias, Alan; Greason, Kevin L; Whisenant, Brian K; Hodson, Robert W; Moses, Jeffrey W; Trento, Alfredo; Brown, David L; Fearon, William F; Pibarot, Philippe; Hahn, Rebecca T; Jaber, Wael A; Anderson, William N; Alu, Maria C; Webb, John G

2016-04-28

Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial.

PubMed

Ali, Mohammad; Debes, Amanda K; Luquero, Francisco J; Kim, Deok Ryun; Park, Je Yeon; Digilio, Laura; Manna, Byomkesh; Kanungo, Suman; Dutta, Shanta; Sur, Dipika; Bhattacharya, Sujit K; Sack, David A

2016-09-01

Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy. This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5-11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%-98%) and 93% (95% CI 44%-99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child (<5 y) or was older. Of note, this study was a reanalysis of a cholera vaccine trial that used two doses; thus, a limitation of the study relates to the assumption that a single dose, if administered quickly, will induce a similar level of total and indirect protection over the short term as did two doses. These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective. ClinicalTrials.gov NCT00289224.

Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial

PubMed Central

Ali, Mohammad; Luquero, Francisco J.; Kim, Deok Ryun; Park, Je Yeon; Digilio, Laura; Manna, Byomkesh; Kanungo, Suman; Dutta, Shanta; Sur, Dipika; Bhattacharya, Sujit K.

2016-01-01

Introduction Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy. Methods and Findings This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals’ vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5–11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%–98%) and 93% (95% CI 44%–99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child (<5 y) or was older. Of note, this study was a reanalysis of a cholera vaccine trial that used two doses; thus, a limitation of the study relates to the assumption that a single dose, if administered quickly, will induce a similar level of total and indirect protection over the short term as did two doses. Conclusions These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective. Trial registration ClinicalTrials.gov NCT00289224 PMID:27622507

First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.

PubMed

Rolan, Paul E; O'Neill, Gilmore; Versage, Eve; Rana, Jitesh; Tang, Yongqiang; Galluppi, Gerald; Aycardi, Ernesto

2015-01-01

To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase. These data support the development of BG00010 for the treatment of neuropathic pain. ClinicalTrials.gov NCT00961766.

Recurrence of tuberculosis among patients following treatment completion in eight provinces of Vietnam: a nested case-control study.

PubMed

Bestrashniy, Jessica Rutledge Bruce Musselman; Nguyen, Viet Nhung; Nguyen, Thi Loi; Pham, Thi Lieu; Nguyen, Thu Anh; Pham, Duc Cuong; Nghiem, Le Phuong Hoa; Le, Thi Ngoc Anh; Nguyen, Binh Hoa; Nguyen, Kim Cuong; Nguyen, Huy Dung; Buu, Tran Ngoc; Le, Thi Nhung; Nguyen, Viet Hung; Dinh, Ngoc Sy; Britton, Warwick John; Marks, Guy Barrington; Fox, Greg James

2018-06-23

Patients completing treatment for tuberculosis (TB) in high-prevalence settings face a risk of developing recurrent disease. This has important consequences for public health, given its association with drug resistance and a poor prognosis. Previous research has implicated individual factors such as smoking, alcohol use, HIV, poor treatment adherence, and drug resistant disease as risk factors for recurrence. However, little is known about how these factors co-act to produce recurrent disease. Furthermore, perhaps factors related to the index disease means higher burden/low resource settings may be more prone to recurrent disease that could be preventable. We conducted a case-control study nested within a cohort of consecutively enrolled adults who were being treated for smear positive pulmonary TB in 70 randomly selected district clinics in Vietnam. Cases were patients with recurrent TB, identified by follow-up from the parent cohort study. Controls were selected from the cohort by random sampling. Information on demographic, clinical and disease-related characteristics was obtained by interview. information was extracted from clinic registries. Logistic regression, with stepwise selection, was used to develop a fully adjusted model for the odds of recurrence of TB. We recruited 10,964 patients between October 2010 and July 2013. Median follow-up was 988 days. At the end of follow-up, 505 patients (4.7%) with recurrence were identified as cases and 630 other patients were randomly selected as controls. Predictors of recurrence included multidrug-resistant (MDR)-TB (adjusted odds ratio 79.6; 95% CI: 25.1-252.0), self-reported prior TB therapy (aOR=2.5; 95% CI: 1.7-3.5), and incomplete adherence (aOR=1.9; 95% CI 1.1-3.1). Index disease treatment history is a leading determinant of relapse among patients with TB in Vietnam. Further research is required to identify interventions that will reduce the risk of recurrent disease and enhance its early detection within high-risk populations. Copyright © 2018. Published by Elsevier Ltd.

Exploring Mechanisms of Effective Teacher Coaching: A Tale of Two Cohorts From a Randomized Experiment

ERIC Educational Resources Information Center

Blazar, David; Kraft, Matthew A.

2015-01-01

Although previous research has shown that teacher coaching can improve teaching practices and student achievement, little is known about specific features of effective coaching programs. We estimate the impact of MATCH Teacher Coaching (MTC) on a range of teacher practices using a blocked randomized trial and explore how changes in the coaching…

Fruit and Vegetable Consumption and Changes in Anthropometric Variables in Adult Populations: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

PubMed Central

Schwingshackl, Lukas; Hoffmann, Georg; Kalle-Uhlmann, Tamara; Arregui, Maria; Buijsse, Brian; Boeing, Heiner

2015-01-01

Background Randomized controlled trials provide conflicting results on the effects of increased fruit and vegetable consumption on changes in body weight. We aimed to perform a systematic review and meta-analysis of prospective cohort studies on fruit and vegetable consumption in relation to changes in anthropometric measures. Methods PubMed and EMBASE were searched up to July 2015 for prospective studies reporting on habitual fruit and/or vegetable consumption in relation to changes in body weight or waist circumference or to risk of weight gain/overweight/obesity in adults. Random-effects meta-analysis was applied to pool results across studies. Findings Seventeen cohort studies (from 20 reports) including 563,277 participants met our inclusion criteria. Higher intake of fruits was inversely associated with weight change (decrease) (beta-coefficient per 100-g increment, -13.68 g/year; 95% CI, -22.97 to -4.40). No significant changes could be observed for combined fruit and vegetable consumption or vegetable consumption. Increased intake of fruits was inversely associated with changes (decrease) in waist circumference (beta: -0.04 cm/year; 95% CI, -0.05 to -0.02). Comparing the highest combined fruit & vegetable, fruit, and vegetable intake categories were associated with a 9%, 17%, and 17% reduced risk of adiposity (odds ratio [OR]: 0.91, 95% CI, 0.84 to 0.99), (OR: 0.83, 95% CI, 0.71 to 0.99), and (OR: 0.83, 95% CI, 0.70 to 0.99), respectively. Conclusion This meta-analysis showed several inverse associations between fruit and vegetable intake and prospective improvements in anthropometric parameters, and risk of adiposity. The present meta-analysis seems to be limited by low study quality. Nevertheless, when combined with evolutionary nutrition and epidemiological modeling studies, these findings have public health relevance and support all initiatives to increase fruit and vegetable intake. PMID:26474158

Increased dementia risk predominantly in diabetes mellitus rather than in hypertension or hyperlipidemia: a population-based cohort study.

PubMed

Fan, Yen-Chun; Hsu, Jung-Lung; Tung, Hong-Yi; Chou, Chia-Chi; Bai, Chyi-Huey

2017-02-06

The pathophysiology of insulin resistance-induced hypertension and hyperlipidemia might entail differences in dementia risk in cases with hypertension and hyperlipidemia without prior diabetes mellitus (DM). This study investigated whether incident hypertension, incident hyperlipidemia, or both, increased the dementia risk in patients with and without DM. A nationwide retrospective cohort study was conducted. The study sample was obtained from the National Health Insurance Research Database. We enrolled 10,316 patients with a new diagnosis of DM between 2000 and 2002 in the DM cohort. For the same period, we randomly selected 41,264 patients without DM in the non-DM cohort (matched by age and sex at a 1:4 ratio with the DM cohort). Both cohorts were then separately divided into four groups on the basis of incident hypertension or incident hyperlipidemia status. In total, 51,580 patients aged between 20 and 99 years were enrolled. The dementia risk was higher in the DM cohort than in the non-DM cohort (adjusted hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.30-1.67, p < 0.001). In the DM cohort, the dementia risk in patients with both hypertension and hyperlipidemia did not significantly increase compared with that in those without hypertension and hyperlipidemia (p = 0.529). Similar results were observed in those with either hypertension (p = 0.341) or hyperlipidemia (p = 0.189). In the non-DM cohort, patients with both hypertension and hyperlipidemia had a higher dementia risk (adjusted HR = 1.33, 95% CI = 1.09-1.63, p = 0.006). The results remained largely unchanged in patients with only hypertension (adjusted HR = 1.22, 95% CI = 1.05-1.40, p = 0.008). However, the dementia risk did not increase significantly in patients with only hyperlipidemia (p = 0.187). The development of hypertension, hyperlipidemia, or both, following a diagnosis of incident diabetes is secondary to diabetes onset and likely mediated through insulin resistance associated with diabetes, which does not further accentuate dementia risk. DM itself (i.e., the systemic influence of hyperglycemia) might be the main driver of increased dementia risk.

Personal hair dyes use and risk of glioma: a meta-analysis

PubMed Central

Shao, Chuan; Qi, Zhen-Yu; Hui, Guo-Zhen; Wang, Zhong

2013-01-01

Background and Objective: Use of hair dyes for glioma risk has been investigated in numerous epidemiological studies, but the evidence is inconsistent. Therefore, a meta-analysis was performed to estimate the association between hair dyes use and glioma risk. Methods: We searched PubMed and EMBASE databases without any limitations, covering all papers published by the end of March 8, 2013. Cohort and case-control studies reporting relative risk estimates (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) on this issue were included. Random effects models were used to calculate the pooled RRs and corresponding 95% CIs. Results: Four case-control and two cohort studies were included in this meta-analysis. The summary RRs and 95 % CIs for ever users of any hair dyes were 1.132 (0.887-1.446) for all studies, 1.291 (0.938-1.777) for case-control studies, and 0.903 (0.774-1.054) for cohort studies. In the subgroup analysis by geographic regions and sex, the similar results were detected. No significant associations were also observed among the studies which reported data involving permanent hair dye use and duration of any hair dye use. Conclusion: In summary, the results of our study demonstrated that hair dyes use is not associated with risk of glioma. PMID:24179568

The cost of institutional care in Alzheimer's disease: nursing home and hospital use in a prospective cohort.

PubMed

Welch, H G; Walsh, J S; Larson, E B

1992-03-01

To assess the nursing home and hospital use of patients with Alzheimer's Type Dementia. A prospective cohort study of 126 patients entered into an Alzheimer's disease registry after diagnosis at a university hospital clinic between 1980 and 1982. Only four patients were in nursing homes at enrollment. Data regarding nursing home use came from the registry and the individual nursing homes themselves. Hospital-use data were obtained using Medicare claims files. Follow-up was obtained on 123 patients (98%). Eighty-five (69%) had died by July 1, 1989. Three-quarters of the cohort (92) eventually resided in nursing homes. The median nursing home length of stay was 2.75 years (mean 2.95, 95% CI = 2.5, 3.4), over 10 times the national median length of stay for all diagnoses. Based on prevailing rates in the region, nursing home charges for the cohort were estimated to be between $4.3 and $6.4 million ($35,000-$52,000 per patient). During the 5-year period 1983-1988, 69 patients filed Part A (hospital) claims to Medicare for 76 admissions and 616 inpatient days. Part A Medicare reimbursement for the cohort totaled $460,000 over 5 years ($3,700 per patient), an expenditure comparable to what a random Medicare cohort might incur. The combination of a high rate of nursing home entry and lengthy stays makes long-term care the largest determinant of the cost of care in Alzheimer's disease. While Alzheimer's Type Dementia undoubtedly has profound indirect costs, this study demonstrates that the direct institutional costs alone are considerable.

Cohort profile: the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) in Korea

PubMed Central

Seong, Sang Cheol; Kim, Yeon-Yong; Park, Sue K; Khang, Young Ho; Kim, Hyeon Chang; Park, Jong Heon; Kang, Hee-Jin; Do, Cheol-Ho; Song, Jong-Sun; Lee, Eun-Joo; Ha, Seongjun; Shin, Soon Ae; Jeong, Seung-Lyeal

2017-01-01

Purpose The National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) is a cohort of participants who participated in health screening programmes provided by the NHIS in the Republic of Korea. The NHIS constructed the NHIS-HEALS cohort database in 2015. The purpose of this cohort is to offer relevant and useful data for health researchers, especially in the field of non-communicable diseases and health risk factors, and policy-maker. Participants To construct the NHIS-HEALS database, a sample cohort was first selected from the 2002 and 2003 health screening participants, who were aged between 40 and 79 in 2002 and followed up through 2013. This cohort included 514 866 health screening participants who comprised a random selection of 10% of all health screening participants in 2002 and 2003. Findings to date The age-standardised prevalence of anaemia, diabetes mellitus, hypertension, obesity, hypercholesterolaemia and abnormal urine protein were 9.8%, 8.2%, 35.6%, 2.7%, 14.2% and 2.0%, respectively. The age-standardised mortality rate for the first 2 years (through 2004) was 442.0 per 100 000 person-years, while the rate for 10 years (through 2012) was 865.9 per 100 000 person-years. The most common cause of death was malignant neoplasm in both sexes (364.1 per 100 000 person-years for men, 128.3 per 100 000 person-years for women). Future plans This database can be used to study the risk factors of non-communicable diseases and dental health problems, which are important health issues that have not yet been fully investigated. The cohort will be maintained and continuously updated by the NHIS. PMID:28947447

The impact of low-dose aspirin on preterm birth: secondary analysis of a randomized controlled trial.

PubMed

Allshouse, A A; Jessel, R H; Heyborne, K D

2016-06-01

The objective of this study is to determine whether low-dose aspirin (LDA) reduced the rate of preterm birth (PTB) in a cohort of women at high risk for preeclampsia. Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin trial. Preterm births were categorized by phenotype: indicated, spontaneous or due to preterm premature rupture of membranes (PPROMs). Of 1789 randomized women, 30.5% delivered before 37 weeks (18.5% indicated, 5.8% spontaneous and 6.2% following preterm PPROMs). Among women randomized to LDA, we observed a trend favoring fewer PTBs due to spontaneous preterm labor and preterm PPROMs, odds ratio (OR: 0.826 (0.620, 1.099)); the incidence of indicated PTBs appeared unchanged, OR: 0.999 (0.787, 1.268). Although not reaching significance, we observed an effect size similar to other studies of both low- and high-risk women. These results support findings from other studies assessing LDA as a PTB prevention strategy.

Citrus fruit intake and bladder cancer risk: a meta-analysis of observational studies.

PubMed

Liang, Sudong; Lv, Gaofei; Chen, Weikai; Jiang, Jianxin; Wang, Jingqun

2014-11-01

Epidemiological studies have investigated the association between citrus fruit and bladder cancer risk; however, the results are inconsistent. To assess these issues, we conducted a meta-analysis of currently available studies. We identified relevant articles by searching the MEDLINE and EMBASE databases. We calculated the summary relative risk (RR) with 95% confidence interval (95% CI) using a random effect model. We included eight case-control studies and six cohort studies in the meta-analysis. There was a significant inverse association between citrus fruit intake and bladder cancer risk in all pooled studies (RR: 0.85; 95% CI, 0.76-0.94) and case-control studies (RR: 0.77; 95% CI, 0.64-0.92), but not in the cohort studies (RR: 0.96; 95% CI, 0.87-1.07). Our results suggest that citrus fruit intake is related to decreased bladder cancer risk. Subsequent well-designed, large prospective studies are needed to obtain better understanding of this relationship.

Risk of hypothyroidism among patients with nasopharyngeal carcinoma treated with radiation therapy: A Population-Based Cohort Study.

PubMed

Fan, Chao-Yueh; Lin, Chun-Shu; Chao, Hsing-Lung; Huang, Wen-Yen; Su, Yu-Fu; Lin, Kuen-Tze; Tsai, I-Ju; Kao, Chia-Hung

2017-06-01

This study aimed to assess the incidence and risk of hypothyroidism among patients with nasopharyngeal carcinoma (NPC) after radiation therapy (RT). We identified 14,893 NPC patients and 16,105 other head and neck cancer (HNC) patients treated with RT without thyroidectomy from the National Health Insurance Research Database in Taiwan between 2000 and 2011. Each NPC patient was randomly frequency-matched with four individuals without NPC by age, sex, and index year. Competing-risk regression models were used to estimate hazard ratios (HRs) of hypothyroidism requiring thyroxin associated with NPC after RT. The risk of developing hypothyroidism was significantly higher in the NPC cohort than in the matched cohort (adjusted HR=14.35, 95% CI=11.85-17.37) and the HNC cohort (adjusted HR=2.06, 95% CI=1.69-2.52). Independent risk factors for hypothyroidism among NPC patients included younger age, female sex, higher urbanization level, autoimmune disease, and receipt of chemotherapy. The risk of hypothyroidism requiring thyroxin was significantly higher in NPC patients after RT than in the general Taiwanese population and HNC patients. Regular clinical and serum thyroid function tests are essential among NPC survivors after RT. Copyright © 2017 Elsevier B.V. All rights reserved.

Do baby walkers delay onset of walking in young children?

PubMed

Burrows, Patricia; Griffiths, Peter

2002-11-01

Baby walkers have been a source of considerable controversy. Some people suggest developmental benefit from their use while others focus on the potential harm that stems from accidents and even suggest developmental delay. This mini-review aimed to determine if use of a baby walker delays affects the onset of walking. The Cochrane library, Embase, CINAHL and Medline were searched for randomized controlled trials (RCTs) and cohort studies, which compared the onset of walking in infants who used baby walkers with a group who did not. Two RCTs and two cohort studies were identified and available for consideration. All of the studies examined the effect of infant walkers on the onset of walking. The results of the two RCTs did not demonstrate a significant effect on the onset of walking. The cohort studies suggest that the use of infant walkers delayed the onset of walking in young children and a pooled analysis of the four studies suggested a delay of between 11 and 26 days. Although the quality of the studies was relatively poor these studies lend no support to the argument that walkers aid the development of walking. The significance of a delay of this magnitude is however unclear. Further work is required to determine whether walkers are an independent causal factor in accidents.

A non-interventional comparative study of the 20:1 combination of cafedrine/theodrenaline versus ephedrine for the treatment of intra-operative arterial hypotension: the 'HYPOTENS' study design and rationale.

PubMed

Eberhart, Leopold; Geldner, Götz; Huljic, Susanne; Marggraf, Kerstin; Keller, Thomas; Koch, Tilo; Kranke, Peter

2018-06-01

To compare the effectiveness of 20:1 cafedrine/theodrenaline approved for use in Germany to ephedrine in the restoration of arterial blood pressure and on post-operative outcomes in patients with intra-operative arterial hypotension of any origin under standard clinical practice conditions. 'HYPOTENS' is a national, multi-center, prospective, open-label, two-armed, non-interventional study. Effectiveness and post-operative outcome following cafedrine/theodrenaline or ephedrine therapy will be evaluated in two cohorts of hypotensive patients. Cohort A includes patients aged ≥50 years with ASA-classification 2-4 undergoing non-emergency surgical procedures under general anesthesia. Cohort B comprises patients undergoing Cesarean section under spinal anesthesia. Participating surgical departments will be assigned to a treatment arm by routinely used anti-hypotensive agent. To minimize bias, matched department pairs will be compared in a stratified selection process. The composite primary end-point is the lower absolute deviation from individually determined target blood pressure (IDTBP) and the incidence of heart rate ≥100 beats/min in the first 15 min. Secondary end-points include incidence and degree of early post-operative delirium (cohort A), severity of fetal acidosis in the newborn (cohort B), upper absolute deviation from IDTBP, percentage increase in systolic blood pressure, and time to IDTBP. This open-label, non-interventional study design mirrors daily practice in the treatment of patients with intra-operative hypotension and ensures full treatment decision autonomy with respect to each patient's individual condition. Selection of participating sites by a randomization process addresses bias without interfering with the non-interventional nature of the study. First results are expected in 2018. ClinicalTrials.gov identifier: NCT02893241; DRKS identifier: DRKS00010740.

Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies.

PubMed

Han, Hedong; Fang, Xin; Wei, Xin; Liu, Yuzhou; Jin, Zhicao; Chen, Qi; Fan, Zhongjie; Aaseth, Jan; Hiyoshi, Ayako; He, Jia; Cao, Yang

2017-05-05

The findings of prospective cohort studies are inconsistent regarding the association between dietary magnesium intake and serum magnesium concentration and the risk of hypertension. We aimed to review the evidence from prospective cohort studies and perform a dose-response meta-analysis to investigate the relationship between dietary magnesium intake and serum magnesium concentrations and the risk of hypertension. We searched systematically PubMed, EMBASE and the Cochrane Library databases from October 1951 through June 2016. Prospective cohort studies reporting effect estimates with 95% confidence intervals (CIs) for hypertension in more than two categories of dietary magnesium intake and/or serum magnesium concentrations were included. Random-effects models were used to combine the estimated effects. Nine articles (six on dietary magnesium intake, two on serum magnesium concentration and one on both) of ten cohort studies, including 20,119 cases of hypertension and 180,566 participates, were eligible for inclusion in the meta-analysis. We found an inverse association between dietary magnesium intake and the risk of hypertension [relative risk (RR) = 0.92; 95% CI: 0.86, 0.98] comparing the highest intake group with the lowest. A 100 mg/day increment in magnesium intake was associated with a 5% reduction in the risk of hypertension (RR = 0.95; 95% CI: 0.90, 1.00). The association of serum magnesium concentration with the risk of hypertension was marginally significant (RR = 0.91; 95% CI: 0.80, 1.02). Current evidence supports the inverse dose-response relationship between dietary magnesium intake and the risk of hypertension. However, the evidence about the relationship between serum magnesium concentration and hypertension is limited.

Mode of delivery affected questionnaire response rates in a birth cohort study.

PubMed

Bray, Isabelle; Noble, Sian; Robinson, Ross; Molloy, Lynn; Tilling, Kate

2017-01-01

Cohort studies must collect data from their participants as economically as possible, while maintaining response rates. This randomized controlled trial investigated whether offering a choice of online or paper questionnaires resulted in improved response rates compared with offering online first. Eligible participants were young people in the Avon Longitudinal Study of Parents and Children (ALSPAC) study (born April 1, 1991, to December 31, 1992, in the Avon area). After exclusions, 8,795 participants were randomized. The "online first" group were invited to complete the questionnaire online. The "choice" group were also sent a paper questionnaire and offered a choice of completion method. The trial was embedded within routine data collection. The main outcome measure was the number of questionnaires returned. Data on costs were also collected. Those in the "online first" arm of the trial were less likely to return a questionnaire [adjusted odds ratio: 0.90; 95% confidence interval (CI): 0.82, 0.99]. The "choice" arm was more expensive (mean difference per participant £0.71; 95% CI: £0.65, £0.76). It cost an extra £47 to have one extra person to complete the questionnaire in the "choice" arm. Offering a choice of completion methods (paper or online) for questionnaires in ALSPAC increased response rates but was more expensive than offering online first. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Lifestyle and specific dietary habits in the Italian population: focus on sugar intake and association with anthropometric parameters-the LIZ (Liquidi e Zuccheri nella popolazione Italiana) study.

PubMed

Marangoni, Franca; Brignoli, Ovidio; Cricelli, Claudio; Poli, Andrea

2017-06-01

In order to collect information on food intake, lifestyle and health status of the Italian population, a random cohort of about 2000 adults was selected in collaboration with the Italian society of general practitioners' network (SIMG). Cohort subjects underwent a full clinical evaluation, by their family doctor, who also collected anthropometric data and information on the prevalence of cardiovascular disease risk factors; they were also administered diary forms developed to assess dietary use of simple sugars, of sugar-containing food and of selected food items. Data obtained indicate that the consumption of simple sugars (either added or as natural part of food) by the Italian adult population is, on average, not high (65 and 67 g/day, among women and men, respectively) and mostly derived from food items such as fruit, milk and yogurt. In addition, no correlations were found, in this low-sugar-consuming cohort, between sugar intake and weight, body mass index and waist circumference. Intakes of simple sugars in the LIZ cohort are not associated with weight, BMI and waist circumference. Prospective data, from cohorts like the LIZ one, might shed further light on the contribution of simple sugar intake to health in countries like Italy.

Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion: A Binational Cohort Study.

PubMed

Halmin, Märit; Rostgaard, Klaus; Lee, Brian K; Wikman, Agneta; Norda, Rut; Nielsen, Kaspar René; Pedersen, Ole B; Holmqvist, Jacob; Hjalgrim, Henrik; Edgren, Gustaf

2017-02-21

Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists. To study the association between the length of RBC storage and mortality in a large population-based cohort of patients who received transfusions, allowing detection of small yet clinically significant effects. Binational cohort study. All transfusion recipients in Sweden and Denmark. 854 862 adult patients who received transfusions from 2003 to 2012. Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox proportional hazards regression. Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days was -0.2% (95% CI, -0.5% to 0.1%). Even among patients who received more than 6 units of RBCs stored for 30 days or longer, the hazard ratio of death was 1.00 (CI, 0.96 to 1.05) compared with those who received no such units. Observational study; risk of confounding by indication. Consistent with previous randomized trials, this study found no association between the length of storage of transfused RBCs and patient mortality. Results were homogeneous, with differences in absolute mortality consistently less than 1% among the most extreme exposure categories. These findings suggest that the current practice of storing RBCs for up to 42 days does not need to be changed. The Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Society for Medical Research, Strategic Research Program in Epidemiology at Karolinska Institutet, and Danish Council for Independent Research.

Gynecological malignancy risk in colorectal cancer survivors: A population-based cohort study.

PubMed

Chang, Wei-Chun; Muo, Chih-Hsin; Liang, Ji-An; Sung, Fung-Chang; Kao, Chia-Hung

2015-10-01

This study was carried out to assess the risk of gynecological malignancy in colorectal cancer survivors using a population-based retrospective cohort study. Using the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 37,176 patients with colorectal cancer diagnosed in 1998-2009, aged 20 years and above, without other cancer history. We also randomly selected 148,700 women without any cancer in the comparison cohort, frequency matched by age and diagnosis date. Incidences and hazards of breast, cervix, endometrial and ovarian cancers were evaluated by 201l. The overall incidence of the 4 types of gynecological cancer was 39.0% higher in colorectal cancer patients than in comparisons (2.99 vs. 2.14 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.46 (95% confidence interval (CI) = 1.31-1.62). Breast cancer accounted for most subsequent cancer. The multivariable Cox method measured HR was the highest for endometrial cancer (3.40, 95% CI = 2.59-4.47) for the colorectal cohort relative to comparisons, followed by ovarian cancer and breast cancer, except cervix cancer. The risk of gynecological malignancies was apparently elevated for colorectal cancer survivors <50 years of age. Follow-up measures are suggested for women with colorectal cancer for early detection and prevention of the subsequent gynecological malignancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

The importance of mean time in therapeutic range for complication rates in warfarin therapy of patients with atrial fibrillation: A systematic review and meta-regression analysis.

PubMed

Vestergaard, Anne Sig; Skjøth, Flemming; Larsen, Torben Bjerregaard; Ehlers, Lars Holger

2017-01-01

\\Anticoagulation is used for stroke prophylaxis in non-valvular atrial fibrillation, amongst other by use of the vitamin K antagonist, warfarin. Quality in warfarin therapy is often summarized by the time patients spend within the therapeutic range (percent time in therapeutic range, TTR). The correlation between TTR and the occurrence of complications during warfarin therapy has been established, but the influence of patient characteristics in that respect remains undetermined. The objective of the present papers was to examine the association between mean TTR and complication rates with adjustment for differences in relevant patient cohort characteristics. A systematic literature search was conducted in MEDLINE and Embase (2005-2015) to identify eligible studies reporting on use of warfarin therapy by patients with non-valvular atrial fibrillation and the occurrence of hemorrhage and thromboembolism. Both randomized controlled trials and observational cohort studies were included. The association between the reported mean TTR and major bleeding and stroke/systemic embolism was analyzed by random-effects meta-regression with and without adjustment for relevant clinical cohort characteristics. In the adjusted meta-regressions, the impact of mean TTR on the occurrence of hemorrhage was adjusted for the mean age and the proportion of populations with prior stroke or transient ischemic attack. In the adjusted analyses on thromboembolism, the proportion of females was, furthermore, included. Of 2169 papers, 35 papers met pre-specified inclusion criteria, holding relevant information on 31 patient cohorts. In univariable meta-regression, increasing mean TTR was significantly associated with a decreased rate of both major bleeding and stroke/systemic embolism. However, after adjustment mean TTR was no longer significantly associated with stroke/systemic embolism. The proportion of residual variance composed by between-study heterogeneity was substantial for all analyses. Although higher mean TTR in warfarin therapy was associated with lower complication rates in atrial fibrillation, the strength of the association was decreased when adjusting for differences in relevant clinical characteristics of the patient cohorts. This study suggests that mainly the safety of warfarin therapy increases with higher mean TTR, whereas effectiveness appears not to be substantially improved. Due to the limitations immanent in the meta-regression methods, the results of the present study should be interpreted with caution. Further research on the association between the quality of warfarin therapy and risk of complications is warranted with adjustment for clinically relevant characteristics.

Relationship between the Mediterranean dietary pattern and musculoskeletal health in children, adolescents, and adults: systematic review and evidence map

PubMed Central

Craig, Jean V; Bunn, Diane K; Hayhoe, Richard P; Appleyard, Will O; Lenaghan, Elizabeth A; Welch, Ailsa A

2017-01-01

Context: An understanding of the modifiable effects of diet on bone and skeletal muscle mass and strength over the life course will help inform strategies to reduce age-related fracture risk. The Mediterranean diet is rich in nutrients that may be important for optimal musculoskeletal health. Objective: The aim of this systematic review was to investigate the relationship between a Mediterranean diet and musculoskeletal outcomes (fracture, bone density, osteoporosis, sarcopenia) in any age group. Data Sources: Ten electronic databases were searched. Study Selection: Randomized controlled trials and prospective cohort studies that investigated a traditional Mediterranean diet, published in any language, were eligible. Studies using other designs or other definitions of the Mediterranean diet were collated separately in an evidence map. Data Extraction: Details on study design, methods, population, dietary intervention or exposure, length of follow-up, and effect on or association with musculoskeletal outcomes were extracted. Results: The search yielded 1738 references. Data from eligible randomized controlled trials (n = 0) and prospective cohort studies (n = 3) were synthesized narratively by outcome for the systematic review. Two of these studies reported on hip fracture incidence, but results were contradictory. A third study found no association between the Mediterranean diet and sarcopenia incidence. Conclusions: Overall, the systematic review and evidence map demonstrate a lack of research to understand the relationship between the Mediterranean diet and musculoskeletal health in all ages. Systematic Review Registration: PROSPERO registration number IDCRD42016037038. PMID:29028268

A 5-Year Follow-up Study on the Relationship between Obstructive Sleep Apnea and Parkinson Disease.

PubMed

Sheu, Jau-Jiuan; Lee, Hsin-Chien; Lin, Herng-Ching; Kao, Li-Ting; Chung, Shiu-Dong

2015-12-15

Sleep disturbances are among the most common nonmotor symptoms of Parkinson disease. However, no large epidemiological data regarding the association between obstructive sleep apnea (OSA) and Parkinson disease have been reported. The goal of this study was to investigate the risk for Parkinson disease during a 5-y follow-up period after a diagnosis of OSA using a population-based dataset. The data for this retrospective longitudinal cohort study were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We identified 1,532 patients with OSA as the study cohort and randomly selected 7,660 patients as the comparison cohort. Each subject was individually followed up for a 5-y period to identify those in whom Parkinson disease subsequently developed. Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-y risk of subsequent Parkinson disease between the study cohort and comparison cohort. Of the 9,192 total patients, Parkinson disease developed in 0.73% during the 5-y follow-up period: 1.24% and 0.63% in the OSA and control cohorts, respectively. After censoring patients who died during the follow-up period and adjusting for socio-demographic characteristics, the hazard ratio (HR) of Parkinson disease during the 5-y follow-up period for patients with OSA was 2.26 (95% confidence interval [CI] = 1.32-3.88) compared with comparison patients. In addition, among females, the adjusted HR of Parkinson disease was 3.54 (95% CI = 1.50-8.34) for patients with OSA compared to patients without OSA. However, among males, there was no significantly increased hazard of Parkinson disease for patients with OSA compared to those without OSA. Female patients with OSA were found to be at a significant risk of subsequent Parkinson disease during a 5-y follow-up period. © 2015 American Academy of Sleep Medicine.

Gender and socioeconomic disparities in BMI trajectories in the Seychelles: a cohort analysis based on serial population-based surveys.

PubMed

Rossi, Isabelle A; Rousson, Valentin; Viswanathan, Bharathi; Bovet, Pascal

2011-12-09

The relationship between body mass index (BMI) and socioeconomic status (SES) tends to change over time and across populations. In this study, we examined, separately in men and women, whether the association between BMI and SES changed over successive birth cohorts in the Seychelles (Indian Ocean, African region). We used data from all participants in three surveys conducted in 1989, 1994 and 2004 in independent random samples of the population aged 25-64 years in the Seychelles (N = 3'403). We used linear regression to model mean BMI according to age, cohort, SES and smoking status, allowing for a quadratic term for age to account for a curvilinear relation between BMI and age and interactions between SES and age and between SES and cohorts to test whether the relation between SES and BMI changed across subsequent cohorts. All analyses were performed separately in men and women. BMI increased with age in all birth cohorts. BMI was lower in men of low SES than high SES but was higher in women of low SES than high SES. In all SES categories, BMI increased over successive cohorts (1.24 kg/m2 in men and 1.51 kg/m2 for a 10-year increase in birth cohorts, p < 0.001). The difference in BMI between men or women of high vs. low SES did not change significantly across successive cohorts (the interaction between SES and year of birth of cohort was statistically not significant). Smoking was associated with lower BMI in men and women (respectively -1.55 kg/m2 and 2.46 kg/m2, p < 0.001). Although large differences exist between men and women, social patterning of BMI did not change significantly over successive cohorts in this population of a middle-income country in the African region.

Study design and "evidence" in patient-oriented research.

PubMed

Concato, John

2013-06-01

Individual studies in patient-oriented research, whether described as "comparative effectiveness" or using other terms, are based on underlying methodological designs. A simple taxonomy of study designs includes randomized controlled trials on the one hand, and observational studies (such as case series, cohort studies, and case-control studies) on the other. A rigid hierarchy of these design types is a fairly recent phenomenon, promoted as a tenet of "evidence-based medicine," with randomized controlled trials receiving gold-standard status in terms of producing valid results. Although randomized trials have many strengths, and contribute substantially to the evidence base in clinical care, making presumptions about the quality of a study based solely on category of research design is unscientific. Both the limitations of randomized trials as well as the strengths of observational studies tend to be overlooked when a priori assumptions are made. This essay presents an argument in support of a more balanced approach to evaluating evidence, and discusses representative examples from the general medical as well as pulmonary and critical care literature. The simultaneous consideration of validity (whether results are correct "internally") and generalizability (how well results apply to "external" populations) is warranted in assessing whether a study's results are accurate for patients likely to receive the intervention-examining the intersection of clinical and methodological issues in what can be called a medicine-based evidence approach. Examination of cause-effect associations in patient-oriented research should recognize both the strengths and limitations of randomized trials as well as observational studies.

Mortality among people who inject drugs: a systematic review and meta-analysis

PubMed Central

Degenhardt, Louisa; Bucello, Chiara; Lemon, James; Wiessing, Lucas; Hickman, Mathew

2013-01-01

Abstract Objective To systematically review cohort studies of mortality among people who inject drugs, examine mortality rates and causes of death in this group, and identify participant- and study-level variables associated with a higher risk of death. Methods Tailored search strings were used to search EMBASE, Medline and PsycINFO. The grey literature was identified through online grey literature databases. Experts were consulted to obtain additional studies and data. Random effects meta-analyses were performed to estimate pooled crude mortality rates (CMRs) and standardized mortality ratios (SMRs). Findings Sixty-seven cohorts of people who inject drugs were identified, 14 of them from low- and middle-income countries. The pooled CMR was 2.35 deaths per 100 person–years (95% confidence interval, CI: 2.12–2.58). SMRs were reported for 32 cohorts; the pooled SMR was 14.68 (95% CI: 13.01–16.35). Comparison of CMRs and the calculation of CMR ratios revealed mortality to be higher in low- and middle-income country cohorts, males and people who injected drugs that were positive for human immunodeficiency virus (HIV). It was also higher during off-treatment periods. Drug overdose and acquired immunodeficiency syndrome (AIDS) were the primary causes of death across cohorts. Conclusion Compared with the general population, people who inject drugs have an elevated risk of death, although mortality rates vary across different settings. Any comprehensive approach to improving health outcomes in this group must include efforts to reduce HIV infection as well as other causes of death, particularly drug overdose. PMID:23554523

Mother's education and offspring asthma risk in 10 European cohort studies.

PubMed

Lewis, Kate Marie; Ruiz, Milagros; Goldblatt, Peter; Morrison, Joana; Porta, Daniela; Forastiere, Francesco; Hryhorczuk, Daniel; Zvinchuk, Oleksandr; Saurel-Cubizolles, Marie-Josephe; Lioret, Sandrine; Annesi-Maesano, Isabella; Vrijheid, Martine; Torrent, Maties; Iniguez, Carmen; Larranaga, Isabel; Harskamp-van Ginkel, Margreet W; Vrijkotte, Tanja G M; Klanova, Jana; Svancara, Jan; Barross, Henrique; Correia, Sofia; Jarvelin, Marjo-Riitta; Taanila, Anja; Ludvigsson, Johnny; Faresjo, Tomas; Marmot, Michael; Pikhart, Hynek

2017-09-01

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.

Chronic heart failure in Japan: implications of the CHART studies.

PubMed

Shiba, Nobuyuki; Shimokawa, Hiroaki

2008-01-01

The prognosis of patients with chronic heart failure (CHF) still remains poor, despite the recent advances in medical and surgical treatment. Furthermore, CHF is a major public health problem in most industrialized countries where the elderly population is rapidly increasing. Although the prevalence and mortality of CHF used to be relatively low in Japan, the disorder has been markedly increasing due to the rapid aging of the society and the Westernization of lifestyle that facilitates the development of coronary artery disease. The Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-1 study was one of the largest cohorts in Japan. The study has clarified the characteristics and prognosis of Japanese patients with CHF, demonstrating that their prognosis was similarly poor compared with those in Western countries. However, we still need evidence for the prevention and treatment of CHF based on the large cohort studies or randomized treatment trials in the Japanese population. Since the strategy for CHF management is now changing from treatment to prevention, a larger-size prospective cohort, called the CHART-2 study, has been initiated to evaluate the risk factors of CHF in Japan. This review summarizes the current status of CHF studies in Japan and discusses their future perspectives.

Occupational exposure to polychlorinated biphenyls and risk of cutaneous melanoma: a meta-analysis.

PubMed

Boffetta, Paolo; Catalani, Simona; Tomasi, Cesare; Pira, Enrico; Apostoli, Pietro

2018-01-01

The aim of this study was to carry out a meta-analysis of studies on exposure to polychlorinated biphenyls (PCBs) and the risk of malignant melanoma (MM). We searched Scopus, PubMed, and reference lists; among 807 potentially relevant articles, we selected those based on 12 populations. Data were extracted according to a standardized form; the Newcastle-Ottawa Scale was used to assess study quality. Meta-analyses were carried out according to fixed-effect and random-effects models. The fixed-effect summary relative risk (RR) for MM was 0.91 [95% confidence interval (CI): 0.82-1.00]; the random-effects summary RR was 1.05 (95% CI: 0.78-1.32). The random-effects summary RR from eight occupational cohorts was 1.13 (95% CI: 0.91-1.35) and that from four community-based studies was 0.84 (95% CI: 0.36-1.31). The quality of the studies and the methods for PCB exposure assessment did not influence the RR. These results do not support the hypothesis of an association between PCB exposure and the risk of MM.

Group music therapy for severe mental illness: a randomized embedded-experimental mixed methods study.

PubMed

Grocke, D; Bloch, S; Castle, D; Thompson, G; Newton, R; Stewart, S; Gold, C

2014-08-01

Music therapy is an innovative approach to support people with severe mental illness (SMI). The aim of the study was to determine whether group music therapy (GMT) positively impacted on quality of life (QoL), social enrichment, self-esteem, spirituality and psychiatric symptoms of participants with SMI and how they experienced the intervention. The primary outcome was QoL; secondary measures assessed social enrichment, self-esteem, spirituality and psychiatric symptoms. The 13-week intervention comprised singing familiar songs and composing original songs recorded in a professional studio. Qualitative data were generated from focus group interviews and song lyric analysis. Ninety-nine adults (57 female) were recruited, with an initial cohort (n = 75) randomized to either: weekly GMT followed by standard care (SC) or SC followed by GMT. Crossover occurred after 13 weeks. Measures were conducted at baseline, 13, 26 and 39 weeks. A second cohort (n = 24) could not be randomized and were assigned to GMT followed by SC. Intention-to-treat analysis showed a significant difference between GMT and SC on QoL and spirituality. This was robust to different assumptions about missing data (listwise deletion, last observation carried forward or multiple imputation). Per-protocol analysis suggested greater benefit for those receiving more sessions. Focus group interview and song lyric analyses suggested that GMT was enjoyable; self-esteem was enhanced; participants appreciated therapists and peers; and although challenges were experienced, the programme was recommended to others. Group music therapy may enhance QoL and spirituality of persons with SMI. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

SMART trial: A randomized clinical trial of self-monitoring in behavioral weight management-design and baseline findings

PubMed Central

Burke, Lora E.; Styn, Mindi A.; Glanz, Karen; Ewing, Linda J.; Elci, Okan U.; Conroy, Margaret B.; Sereika, Susan M.; Acharya, Sushama D.; Music, Edvin; Keating, Alison L.; Sevick, Mary Ann

2009-01-01

Background The primary form of treatment for obesity today is behavioral therapy. Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change. The SMART weight loss trial examined the impact of replacing the standard paper record used for self-monitoring with a personal digital assistant (PDA). This paper describes the design, methods, intervention, and baseline sample characteristics of the SMART trial. Methods The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention. Participants were randomized to one of three conditions (1) use of a standard paper record (PR); (2) use of a PDA with dietary and physical activity software (PDA); or (3), use of a PDA with the same software plus a customized feedback program (PDA + FB). Results We screened 704 individuals and randomized 210. There were statistically but not clinically significant differences among the three cohorts in age, education, HDL cholesterol, blood glucose and systolic blood pressure. At 24 months, retention rate for the first of three cohorts was 90%. Conclusions To the best of our knowledge, the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records. This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component. PMID:19665588

Transforaminal lumbar interbody graft placement using an articulating delivery arm facilitates increased segmental lordosis with superior anterior and midline graft placement.

PubMed

Shau, David N; Parker, Scott L; Mendenhall, Stephen K; Zuckerman, Scott L; Godil, Saniya S; Devin, Clinton J; McGirt, Matthew J

2015-05-01

Transforaminal lumbar interbody fusion (TLIF) is a frequently performed method of lumbar arthrodesis in patients failing medical management of back and leg pain. Accurate placement of the interbody graft and restoration of lordosis has been shown to be crucial when performing lumbar fusion procedures. We performed a single-surgeon, prospective, randomized study to determine whether a novel articulating versus traditional straight graft delivery arm system allows for superior graft placement and increased lordosis for single-level TLIF. Thirty consecutive patients undergoing single-level TLIF were included and prospectively randomized to one of the 2 groups (articulated vs. straight delivery arm system). Three radiographic characteristics were evaluated at 6-week follow-up: (1) degree of segmental lumbar lordosis at the fused level; (2) the percent anterior location of the interbody graft in disk space; and (3) the distance (mm) off midline of the interbody graft placement. Randomization yielded 16 patients in the articulated delivery arm cohort and 14 in the straight delivery arm cohort. The articulating delivery arm system yielded an average of 14.7-degree segmental lordosis at fused level, 35% anterior location, and 3.6 mm off midline. The straight delivery arm system yielded an average of 10.7-degree segmental lordosis at fused level, 46% anterior location, and 7.0 mm off midline. All 3 comparisons were statistically significant (P<0.05). The study suggests that an articulating delivery arm system facilitates superior anterior and midline TLIF graft placement allowing for increased segmental lordosis compared with a traditional straight delivery arm system.

A review of job-exposure matrix methodology for application to workers exposed to radiation from internally deposited plutonium or other radioactive materials.

PubMed

Liu, Hanhua; Wakeford, Richard; Riddell, Anthony; O'Hagan, Jacqueline; MacGregor, David; Agius, Raymond; Wilson, Christine; Peace, Mark; de Vocht, Frank

2016-03-01

Any potential health effects of radiation emitted from radionuclides deposited in the bodies of workers exposed to radioactive materials can be directly investigated through epidemiological studies. However, estimates of radionuclide exposure and consequent tissue-specific doses, particularly for early workers for whom monitoring was relatively crude but exposures tended to be highest, can be uncertain, limiting the accuracy of risk estimates. We review the use of job-exposure matrices (JEMs) in peer-reviewed epidemiological and exposure assessment studies of nuclear industry workers exposed to radioactive materials as a method for addressing gaps in exposure data, and discuss methodology and comparability between studies. We identified nine studies of nuclear worker cohorts in France, Russia, the USA and the UK that had incorporated JEMs in their exposure assessments. All these JEMs were study or cohort-specific, and although broadly comparable methodologies were used in their construction, this is insufficient to enable the transfer of any one JEM to another study. Moreover there was often inadequate detail on whether, or how, JEMs were validated. JEMs have become more detailed and more quantitative, and this trend may eventually enable better comparison across, and the pooling of, studies. We conclude that JEMs have been shown to be a valuable exposure assessment methodology for imputation of missing exposure data for nuclear worker cohorts with data not missing at random. The next step forward for direct comparison or pooled analysis of complete cohorts would be the use of transparent and transferable methods.

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort

PubMed Central

Merhi, Basma; Shireman, Theresa; Carpenter, Myra A.; Kusek, John W.; Jacques, Paul; Pfeffer, Marc; Rao, Madhumathi; Foster, Meredith C.; Kim, S. Joseph; Pesavento, Todd E.; Smith, Stephen R.; Kew, Clifton E.; House, Andrew A.; Gohh, Reginald; Weiner, Daniel E.; Levey, Andrew S.; Ix, Joachim H.; Bostom, Andrew

2017-01-01

Background Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality. Study Design Cohort study. Setting & Participants The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B–based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs. Predictor Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization. Results During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92–1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15–1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04–1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00–1.31), transplant failure (HR, 1.72; 95% CI, 1.46–2.01), and mortality (HR, 1.34; 95% CI, 1.15–1.54). Limitations We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites. Conclusions Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted. PMID:28579423

Interactive spaced-education to teach the physical examination: a randomized controlled trial.

PubMed

Kerfoot, B Price; Armstrong, Elizabeth G; O'Sullivan, Patricia N

2008-07-01

Several studies have documented that physical examination knowledge and skills are limited among medical trainees. The objective of the study is to investigate the efficacy and acceptability of a novel online educational methodology termed 'interactive spaced-education' (ISE) as a method to teach the physical examination. The design of the study is randomized controlled trial. All 170 second-year students in the physical examination course at Harvard Medical School were eligible to enroll. Spaced-education items (questions and explanations) were developed on core physical examination topics and were content-validated by two experts. Based on pilot-test data, 36 items were selected for inclusion. Students were randomized to start the 18-week program in November 2006 or 12 weeks later. Students were sent 6 spaced-education e-mails each week for 6 weeks (cycle 1) which were then repeated in two subsequent 6-week cycles (cycles 2 and 3). Students submitted answers to the questions online and received immediate feedback. An online end-of-program survey was administered. One-hundred twenty students enrolled in the trial. Cycles 1, 2, and 3 were completed by 88%, 76%, and 71% of students, respectively. Under an intent-to-treat analysis, cycle 3 scores for cohort A students [mean 74.0 (SD 13.5)] were significantly higher than cycle 1 scores for cohort B students [controls; mean 59.0 (SD 10.5); P < .001], corresponding to a Cohen's effect size of 1.43. Eighty-five percent of participants (102 of 120) recommended the ISE program for students the following year. ISE can generate significant improvements in knowledge of the physical examination and is very well-accepted by students.

Population-based breast cancer screening in a primary care network

PubMed Central

Atlas, Steven J.; Ashburner, Jeffrey M.; Chang, Yuchiao; Lester, William T.; Barry, Michael J.; Grant, Richard W.

2013-01-01

Objective To assess up to 3-year follow-up of a health information technology system that facilitated population-based breast cancer screening. Study Design Cohort study with 2-year follow-up after completing a 1-year cluster randomized trial. Methods Women 42-69 years old receiving care within a 12-practice primary care network. The trial tested an integrated, non-visit-based population management informatics system that: 1) identified women overdue for mammograms, 2) connected them to primary care providers using a Web-based tool, 3) created automatically-generated outreach letters for patients specified by providers, 4) monitored for subsequent mammography scheduling and completion, and 5) provided practice delegates a list of women remaining unscreened for reminder phone calls. All practices also provided visit-based cancer screening reminders. Eligible women overdue for a mammogram during a one-year study period included those overdue at study start (prevalent cohort) or becoming overdue during follow-up (incident cohort). The main outcome measure was mammography completion rates over three years. Results Among 32,688 eligible women, 9,795 (30%) were overdue for screening including 4,487 in intervention and 5,308 in control practices. Intervention patients were somewhat younger, more likely to be non-Hispanic white, and have health insurance compared to control patients. Among patients in the prevalent cohort (n=6,697), adjusted completion rates were significantly higher among intervention compared to control patients after 3 years (51.7% vs. 45.8%, p=0.002). For patients in the incident cohort (n=3,098), adjusted completion rates after 2 years were 53.8% vs. 48.7%, p=0.052, respectively. Conclusions Population-based informatics systems can enable sustained increases in mammography screening rates beyond that seen with office-based visit reminders. PMID:23286611

Educational achievements of children of parents with multiple sclerosis: A nationwide register-based cohort study.

PubMed

Moberg, J Y; Magyari, M; Koch-Henriksen, N; Thygesen, L C; Laursen, B; Soelberg Sørensen, P

2016-11-01

Little is known about the impact of parental multiple sclerosis (MS) on offspring's educational attainment. The objective of the study was to examine educational achievements in offspring of parents with MS compared with matched children of parents without MS in a nationwide register-based cohort study. Children of all Danish-born residents with onset between 1950 and 1986 were identified by linking the Danish Multiple Sclerosis Registry with the Civil Registration System. Twins, children with MS, and emigrated persons were excluded. The reference cohort consisted of randomly drawn individuals from the Civil Registration System without parental MS matched 8:1 to the MS offspring by sex and year of birth. Information about education was linked to the cohorts from nationwide educational registries. We included 4177 children of MS parents and 33,416 reference persons. Children of MS parents achieved statistically significant higher average grades than the reference cohort in their final exam of basic school with a mean grade difference of 0.46 (95 % CI 0.22-0.69; p = 0.0002). We found no difference in achievement of educational level above basic school (OR 1.04; 95 % CI 0.98-1.10; p = 0.20). There was a trend toward more MS offspring attaining health-related educations (OR 1.10; 95 % CI 1.00-1.21; p = 0.06). In conclusion, children of MS parents showed a small advantage in grade point average in final examinations in basic school, and they more often tended toward health-related educations. This study revealed no negative consequences of parental MS on grades and highest educational level achieved.

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

PubMed

Nichols, Blake; Kubis, Sherri; Hewlett, Jennifer; Yehya, Nadir; Srinivasan, Vijay

2017-09-01

The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. Retrospective cohort study. Non-cardiac PICU. Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. None. The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 μg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 μg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 μg/dL (all p < 0.05). Children with stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p < 0.05). Mean random serum total cortisol levels were similar in children with and without stress dose hydrocortisone (21.1 vs 18.7 μg/dL; p = 0.69). In children with random serum total cortisol less than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p < 0.05). In children with random serum total cortisol greater than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU mortality and fewer ventilator-free days and vasopressor-free days (all p < 0.05). Stress dose hydrocortisone therapy in children with catecholamine-dependent septic shock correlated more with severity of illness than random serum total cortisol levels and was associated with worse outcomes, irrespective of random serum total cortisol levels.

Dentist age, period and cohort effects on provision of dental services in Australia: 1983-84 to 2009-10.

PubMed

Ju, Xiangqun; Spencer, A John; Brennan, David S

2017-06-01

To examine age, period and cohort factors of dentists in relation to diagnostic, preventive and total dental services over time in Australia. The Longitudinal Study of Dentists' Practice Activity (LSDPA) was designed to monitor dental practice activity and service provision in Australia. Participating dentists were sampled randomly from the dental registers in Australia from 1983 to 1984, and dental services provision was collected by mailed questionnaire with a log of dental services provided over one or two typical days. The data collection has been repeated every 5 years until 2009-2010. Sample supplementation of newly registered dentists occurred at successive waves. This study focused on diagnostic, preventive and total services. The time trends in the mean rates of the services were described using a standard cohort table, and negative binomial regression was applied to estimate age, period and cohort effects. The response rates were 73%, 75%, 74%, 71%, 76% and 67% in 1983, 1988, 1993, 1998, 2003 and 2009, respectively. The mean rates of diagnostic, preventive and total services increased between 1983 and 2009 across all age groups. The period effect showed a higher rate of diagnostic (rate ratios [RR]: 1.21 in 1993 to 1.80 in 2009), preventive (RR: 1.19 in 1988 to 1.85 in 2009) and the total service (RR: 1.08 in 1988 to 1.39 in 2009) over time, compared with the reference group of 1983. Older cohorts had a lower rate, and the younger cohorts had a higher rate of diagnostic, preventive and the total number of services over the study period. The highest rate of diagnostic (RR=2.53), preventive (RR=2.44) and the total service (RR=1.52) was in those aged 25-29 years in 1983 compared with the reference group of 30-34 years in 1983. Trends in dental services provision can be associated with age, period and cohort effects. The study found the rate of diagnostic, preventive and total services increased over time. Meanwhile, an increasing rate of diagnostic, preventive and the total services was observed when moving from older cohorts to younger cohorts among Australian dentists suggesting a sustained shift towards these services into the future. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study.

PubMed

Santos, Michele Devido; Gagliardi, Rubens José; Mac-Kay, Ana Paula Machado Goyano; Boggio, Paulo Sergio; Lianza, Roberta; Fregni, Felipe

2013-01-01

Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. Prospective cohort study developed in a public university hospital. Nineteen patients with chronic aphasia received 10 transcranial direct current stimulation sessions lasting 20 minutes each on consecutive days, using a current of 2 mA. The anode was positioned over the supraorbital area and the cathode over the contralateral motor cortex. The following variables were analyzed before and after the 10 neuromodulation sessions: oral language comprehension, copying, dictation, reading, writing, naming and verbal fluency. There were no adverse effects in the study. We found statistically significant differences from before to after stimulation in relation to simple sentence comprehension (P = 0.034), naming (P = 0.041) and verbal fluency for names of animals (P = 0.038). Improved scores for performing these three tasks were seen after stimulation. We observed that excitability of the primary motor cortex through transcranial direct current stimulation was associated with effects on different aspects of language. This can contribute towards future testing in randomized controlled trials.

Jim Crow and premature mortality among the US Black and White population, 1960-2009: an age-period-cohort analysis.

PubMed

Krieger, Nancy; Chen, Jarvis T; Coull, Brent A; Beckfield, Jason; Kiang, Mathew V; Waterman, Pamela D

2014-07-01

Scant research has analyzed the health impact of abolition of Jim Crow (ie, legal racial discrimination overturned by the US 1964 Civil Rights Act). We used hierarchical age-period-cohort models to analyze US national black and white premature mortality rates (death before 65 years of age) in 1960-2009. Within a context of declining US black and white premature mortality rates and a persistent 2-fold excess black risk of premature mortality in both the Jim Crow and non-Jim Crow states, analyses including random period, cohort, state, and county effects and fixed county income effects found that, within the black population, the largest Jim Crow-by-period interaction occurred in 1960-1964 (mortality rate ratio [MRR] = 1.15 [95% confidence interval = 1.09-1.22), yielding the largest overall period-specific Jim Crow effect MRR of 1.27, with no such interactions subsequently observed. Furthermore, the most elevated Jim Crow-by-cohort effects occurred for birth cohorts from 1901 through 1945 (MRR range = 1.05-1.11), translating to the largest overall cohort-specific Jim Crow effect MRRs for the 1921-1945 birth cohorts (MRR ~ 1.2), with no such interactions subsequently observed. No such interactions between Jim Crow and either period or cohort occurred among the white population. Together, the study results offer compelling evidence of the enduring impact of both Jim Crow and its abolition on premature mortality among the US black population, although insufficient to eliminate the persistent 2-fold black excess risk evident in both the Jim Crow and non-Jim Crow states from 1960 to 2009.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

PubMed

Greene, Stephen J; Epstein, Stephen E; Kim, Raymond J; Quyyumi, Arshed A; Cole, Robert T; Anderson, Allen S; Wilcox, Jane E; Skopicki, Hal A; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I; Gheorghiade, Mihai; Butler, Javed

2017-04-01

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

Randomized controlled trials and neuro-oncology: should alternative designs be considered?

PubMed

Mansouri, Alireza; Shin, Samuel; Cooper, Benjamin; Srivastava, Archita; Bhandari, Mohit; Kondziolka, Douglas

2015-09-01

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.

Age-related Cataract in a Randomized Trial of Selenium and Vitamin E in Men: The SELECT Eye Endpoints (SEE) Study

PubMed Central

Christen, William G.; Glynn, Robert J.; Gaziano, J. Michael; Darke, Amy K.; Crowley, John J.; Goodman, Phyllis J.; Lippman, Scott M.; Lad, Thomas E.; Bearden, James D.; Goodman, Gary E.; Minasian, Lori M.; Thompson, Ian M.; Blanke, Charles D.; Klein, Eric A.

2014-01-01

Importance Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized trials of vitamin E supplements and cataract have been disappointing, and are not yet available for selenium. Objective To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men. Design, Setting, and Participants The SELECT Eye Endpoints (SEE) study was an ancillary study of the SWOG-coordinated Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, placebo-controlled, four arm trial of selenium and vitamin E conducted among 35,533 men aged 50 years and older for African Americans and 55 and older for all other men, at 427 participating sites in the US, Canada, and Puerto Rico. A total of 11,267 SELECT participants from 128 SELECT sites participated in the SEE ancillary study. Intervention Individual supplements of selenium (200 µg/d from L-selenomethionine) and vitamin E (400 IU/d of all rac-α-tocopheryl acetate). Main Outcome Measures Incident cataract, defined as a lens opacity, age-related in origin, responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review, and cataract extraction, defined as the surgical removal of an incident cataract. Results During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio [HR], 0.91; 95 percent confidence interval [CI], 0.75 to 1.11; P=.37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (HR, 1.02; CI, 0.84 to 1.25; P=.81). Similar results were observed for cataract extraction. Conclusions and Relevance These randomized trial data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract. PMID:25232809

Adherence to Mediterranean diet and risk of developing cognitive disorders: An updated systematic review and meta-analysis of prospective cohort studies

PubMed Central

Wu, Lei; Sun, Dali

2017-01-01

Recent articles have presented inconsistent findings on the impact of Mediterranean diet in the occurrence of cognitive disorders; therefore, we performed an updated systematic review and meta-analysis to evaluate the potential association and dose-response pattern with accumulating evidence. We searched the PubMed and the Embase for the records relevant to this topic. A generic inverse-variance method was used to pool the outcome data for continuous variable, and categories of high vs. low, median vs. low of Mediterranean diet score with a random-effects model. Generalized least-squares trend estimation model was used to estimate the potential dose-response patterns of Mediterranean diet score on incident cognitive disorders. We identified 9 cohort studies involving 34,168 participants. Compared with the lowest category, the pooled analysis showed that the highest Mediterranean diet score was inversely associated with the developing of cognitive disorders, and the pooled RR (95% CI) was 0.79 (0.70, 0.90). Mediterranean diet score of the median category was not significantly associated with cognitive disorders. Dose-response analysis indicated a trend of an approximately linear relationship of the Mediterranean diet score with the incident risk of cognitive disorders. Further studies of randomized controlled trials are warranted to confirm the observed association in different populations. PMID:28112268

Predictors of anxiety and depression among people attending diabetes screening: a prospective cohort study embedded in the ADDITION (Cambridge) randomized control trial.

PubMed

Paddison, C A M; Eborall, H C; French, D P; Kinmonth, A L; Prevost, A T; Griffin, S J; Sutton, S

2011-02-01

This study aimed to identify factors predicting anxiety and depression among people who attend primary care-based diabetes screening. A prospective cohort study embedded in the ADDITION (Cambridge) randomized control trial. Participants (N= 3,240) at risk of diabetes were identified from 10 primary care practices and invited to a stepwise screening programme as part of the ADDITION (Cambridge) trial. Main outcome measures were anxiety and depression at 12 months post-screening assessed using the Hospital Anxiety and Depression Scale (HADS). Hierarchical linear regressions showed that demographic, clinical, and psychological variables collectively accounted for 52% of the variance in HADS anxiety scores and 53% of the variance in HADS depression scores 12 months after diabetes screening. Screening outcome (positive or negative for diabetes) was not related to differences in anxiety or depression at 12 months. Higher number of self-reported (diabetes) symptoms after first attendance was associated with higher anxiety and depression at 12-month follow-up, after controlling for anxiety and depression after first attendance. Participants in a diabetes screening programme showed low scores on anxiety and depression scales after first appointment and 1 year later. Diagnosis of diabetes was shown to have a limited psychological impact and may be less important than symptom perception in determining emotional outcomes after participation in diabetes screening. ©2010 The British Psychological Society.

Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults.

PubMed

Claeys, Carine; Drame, Mamadou; García-Sicilia, José; Zaman, Khalequ; Carmona, Alfonso; Tran, Phu My; Miranda, Mariano; Martinón-Torres, Federico; Thollot, Franck; Horn, Michael; Schwarz, Tino F; Behre, Ulrich; Merino, José M; Sadowska-Krawczenko, Iwona; Szymański, Henryk; Schu, Peter; Neumeier, Elisabeth; Li, Ping; Jain, Varsha K; Innis, Bruce L

2018-04-18

GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18-49 years; N = 120), children (3-17 years; N = 821), and infants (6-35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 μg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. ClinicalTrials.gov: NCT02207413 ; trial registration date: August 4, 2014.

Characterizing Time to Diagnostic Resolution After an Abnormal Cancer Screening Exam in Older Adult Participants in the Ohio Patient Navigation Research Program.

PubMed

DeSalvo, Jennifer M; Young, Gregory S; Krok-Schoen, Jessica L; Paskett, Electra D

2017-06-01

This study aims to test the effectiveness of a patient navigation (PN) intervention to reduce time to diagnostic resolution among older adults age ≥65 years versus those <65 years with abnormal breast, cervical, or colorectal cancer screening exams participating in the Ohio Patient Navigation Research Program (OPNRP). The OPNRP utilized a nested cohort group-randomized trial design to randomize 862 participants ( n = 67 for ≥65 years; n = 795 for <65 years) to PN or usual care conditions. A shared frailty Cox model tested the effect of PN on time to resolution. Older adult participants randomized to PN achieved a 6-month resolution rate that was 127% higher than those randomized to usual care ( p = .001). This effect was not significantly different from participants <65 years. PN significantly reduced time to diagnostic resolution among older adults beginning 6 months after an abnormal cancer screening exam. Health care systems should include this population in PN programs to reduce cancer disparities.

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

PubMed Central

Joehanes, Roby; Liu, Chunyu; Aslibekyan, Stella; Demerath, Ellen W.; Guan, Weihua; Zhi, Degui; Willinger, Christine; Courchesne, Paul; Multhaup, Michael; Irvin, Marguerite R.; Schadt, Eric E.; Bressler, Jan; North, Kari; Sundström, Johan; Gustafsson, Stefan; Shah, Sonia; McRae, Allan F.; Harris, Sarah E.; Gibson, Jude; Redmond, Paul; Corley, Janie; Starr, John M.; Visscher, Peter M.; Wray, Naomi R.; Krauss, Ronald M.; Feinberg, Andrew; Fornage, Myriam; Pankow, James S.; Lind, Lars; Fox, Caroline; Ingelsson, Erik; Arnett, Donna K.; Boerwinkle, Eric; Liang, Liming; Levy, Daniel; Deary, Ian J.

2017-01-01

Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases. PMID:28095459

A phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-063, a selective PDE10A inhibitor.

PubMed

Tsai, Max; Chrones, Lambros; Xie, Jinhui; Gevorkyan, Hakop; Macek, Thomas A

2016-10-01

Schizophrenia is a complex neuropsychiatric disorder characterized, in part, by impaired dopamine signaling. TAK-063 is a selective inhibitor of phosphodiesterase 10A, a key regulator of intracellular signaling pathways that is highly expressed in the striatum. Safety, tolerability, and pharmacokinetics of TAK-063 were evaluated in a phase 1 study. Healthy Japanese and non-Japanese volunteers were randomized into dose cohorts of 3, 10, 30, 100, 300, and 1000 mg. Each fasting volunteer randomly received a single dose of TAK-063 or placebo. Individuals from the 100-mg cohort also received a post-washout, 100-mg dose under fed conditions. A total of 84 volunteers enrolled (14 per cohort). The most common drug-related adverse events (AEs) were somnolence (33.3 %), orthostatic tachycardia (19.7 %), and orthostatic hypotension (9.1 %). The three severe AEs recorded occurred at the highest doses: orthostatic hypotension (n = 1; 300 mg) and somnolence (n = 2; 1000 mg). There were no deaths, serious AEs, or discontinuations due to AEs. TAK-063 exposure increased in a dose-dependent manner. Median T max was reached 3 to 4 h postdose. Fed conditions slowed absorption (T max =  6 h) and increased oral bioavailability. Renal elimination was negligible. Safety and pharmacokinetic parameters were similar between Japanese and non-Japanese subjects. Impairments in cognitive function consistent with the effects of other sedative or hypnotic agents were detected using a validated, computerized cognition battery, CNS Vital Signs. TAK-063 was safe and well tolerated at doses up to 1000 mg and demonstrated a pharmacokinetic profile supporting once-daily dosing. Further evaluation of the clinical safety and efficacy of TAK-063 is warranted.

Clinical and laboratory characteristics of active and healthy aging (AHA) in octogenarian men.

PubMed

Rantanen, Kirsi K; Strandberg, Timo E; Stenholm, Sari S; Strandberg, Arto Y; Pitkälä, Kaisu H; Salomaa, Veikko V; Tilvis, Reijo S

2015-10-01

To investigate clinical and laboratory variables associated with good subjective and objective health ("active and healthy aging", AHA) in a cohort of octogenarian men. Cross-sectional analyses of a longitudinal study. The Helsinki Businessmen Study in Finland. A socioeconomically homogenous cohort of men (baseline n = 3293), born in 1919-1934, has been followed up from the 1960s. From 2000, the men have been regularly sent mailed questionnaires and mortality has been retrieved from national registers. In 2010 survey, AHA was defined as independently responding to the mailed survey, feeling happy without cognitive or functional impairments and without major diseases. In 2010/11, a random subgroup men was clinically investigated and survivors with healthy and nonhealthy aging were compared. By 2010, 1788 men of the baseline cohort had died, and 894 men responded to the mailed survey. 154 (17.2 %) of those fulfilled the present AHA criteria. Increasing number of criteria were negatively (P < 0.001) related to short-term mortality. In 2011, a random sample of 458 men were clinically investigated, 90 of them with AHA. Men with AHA had higher serum LDL cholesterol and diastolic blood pressure (partially explained by less frequent drug use) but no significant difference was observed in other risk factors. Men with AHA had significantly faster walking speed (P < 0.001), stronger handgrip (P = 0.017), better self-rated health and less phenotypic frailty (P = 0.02). Less than 5 % enjoyed active and healthy aging over their life course, which was significantly related to markers of frailty but not to the traditional vascular risk factors.

Neuromuscular exercise and counseling decrease absenteeism due to low back pain in young conscripts: a randomized, population-based primary prevention study.

PubMed

Suni, Jaana H; Taanila, Henri; Mattila, Ville M; Ohrankämmen, Olli; Vuorinen, Petteri; Pihlajamäki, Harri; Parkkari, Jari

2013-03-01

Controlled intervention with group randomization. To investigate the effectiveness of a 6-month neuromuscular exercise and counseling program for reducing the incidence of low back pain (LBP) and disability in young conscripts, with a healthy back at the beginning of their compulsory military service. Basic military training is physically demanding on the back and requires adequate physical fitness. LBP causes significant morbidity and absence from military service. Participants were conscripts of 4 successive age cohorts (n = 1409). In the prestudy year, before adoption of the intervention, 2 successive cohorts of conscripts of 4 companies (n = 719) were followed prospectively for 6 months to study the baseline incidence of different categories of LBP. In the intervention year, conscripts (n = 690) of 2 new cohorts of the same companies (intervention group: antitank, engineer; control group: signal, mortar) were followed for 6 months. The intervention program aimed to improve conscripts' control of their lumbar neutral zone and specifically to avoid full lumbar flexion in all daily tasks. Total number and incidence of off-duty days due to LBP were significantly decreased in the intervention companies compared with controls (adjusted hazard ratio = 0.42, 95% confidence interval = 0.18-0.94, P = 0.035). The number of LBP cases, number of health clinic visits due to LBP, and number of the most severe cases showed a similar decreasing trend but without statistical significance. These findings provide evidence that exercise and education to improve control of the lumbar neutral zone have a prophylactic effect on LPB-related off-duty service days in the military environment when implemented as part of military service among young healthy men.

Operationalizing multimorbidity and autonomy for health services research in aging populations - the OMAHA study

PubMed Central

2011-01-01

Background As part of a Berlin-based research consortium on health in old age, the OMAHA (Operationalizing Multimorbidity and Autonomy for Health Services Research in Aging Populations) study aims to develop a conceptual framework and a set of standardized instruments and indicators for continuous monitoring of multimorbidity and associated health care needs in the population 65 years and older. Methods/Design OMAHA is a longitudinal epidemiological study including a comprehensive assessment at baseline and at 12-month follow-up as well as brief intermediate telephone interviews at 6 and 18 months. In order to evaluate different sampling procedures and modes of data collection, the study is conducted in two different population-based samples of men and women aged 65 years and older. A geographically defined sample was recruited from an age and sex stratified random sample from the register of residents in Berlin-Mitte (Berlin OMAHA study cohort, n = 299) for assessment by face-to-face interview and examination. A larger nationwide sample (German OMAHA study cohort, n = 730) was recruited for assessment by telephone interview among participants in previous German Telephone Health Surveys. In both cohorts, we successfully applied a multi-dimensional set of instruments to assess multimorbidity, functional disability in daily life, autonomy, quality of life (QoL), health care services utilization, personal and social resources as well as socio-demographic and biographical context variables. Response rates considerably varied between the Berlin and German OMAHA study cohorts (22.8% vs. 59.7%), whereas completeness of follow-up at month 12 was comparably high in both cohorts (82.9% vs. 81.2%). Discussion The OMAHA study offers a wide spectrum of data concerning health, functioning, social involvement, psychological well-being, and cognitive capacity in community-dwelling older people in Germany. Results from the study will add to methodological and content-specific discourses on human resources for maintaining quality of life and autonomy throughout old age, even in the face of multiple health complaints. PMID:21352521

Long working hours and depressive symptoms: systematic review and meta-analysis of published studies and unpublished individual participant data.

PubMed

Virtanen, Marianna; Jokela, Markus; Madsen, Ida Eh; Magnusson Hanson, Linda L; Lallukka, Tea; Nyberg, Solja T; Alfredsson, Lars; Batty, G David; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Erbel, Raimund; Ferrie, Jane E; Heikkilä, Katriina; Knutsson, Anders; Koskenvuo, Markku; Lahelma, Eero; Nielsen, Martin L; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Rahkonen, Ossi; Rugulies, Reiner; Salo, Paula; Schupp, Jürgen; Shipley, Martin J; Siegrist, Johannes; Singh-Manoux, Archana; Suominen, Sakari B; Theorell, Töres; Vahtera, Jussi; Wagner, Gert G; Wang, Jian Li; Yiengprugsawan, Vasoontara; Westerlund, Hugo; Kivimäki, Mika

2018-05-01

Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published prospective cohort studies and included available cohorts with unpublished individual-participant data. We used a random-effects meta-analysis to calculate summary estimates across studies. Results We identified ten published cohort studies and included unpublished individual-participant data from 18 studies. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2 =45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association in Europe (1.11, 95% CI 1.00-1.22), and no association in North America (0.97, 95% CI 0.70-1.34) or Australia (0.95, 95% CI 0.70-1.29). Differences by other characteristics were small. Conclusions This observational evidence suggests a moderate association between long working hours and onset of depressive symptoms in Asia and a small association in Europe.

Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.

PubMed

Lawitz, Eric; Sulkowski, Mark S; Ghalib, Reem; Rodriguez-Torres, Maribel; Younossi, Zobair M; Corregidor, Ana; DeJesus, Edwin; Pearlman, Brian; Rabinovitz, Mordechai; Gitlin, Norman; Lim, Joseph K; Pockros, Paul J; Scott, John D; Fevery, Bart; Lambrecht, Tom; Ouwerkerk-Mahadevan, Sivi; Callewaert, Katleen; Symonds, William T; Picchio, Gaston; Lindsay, Karen L; Beumont, Maria; Jacobson, Ira M

2014-11-15

Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir. We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790. 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12. Combined simeprevir and sofosbuvir was efficacious and well tolerated. Janssen. Copyright © 2014 Elsevier Ltd. All rights reserved.

COMPLETE - a school-based intervention project to increase completion of upper secondary school in Norway: study protocol for a cluster randomized controlled trial.

PubMed

Larsen, T; Urke, H B; Holsen, I; Anvik, C H; Olsen, T; Waldahl, R H; Antonsen, K M; Johnson, R; Tobro, M; Brastad, B; Hansen, T B

2018-03-09

Drop out from upper secondary school represents a risk for the future health and wellbeing of young people. Strengthening of psychosocial aspects of the learning environment may be an effective strategy to promote completion of upper secondary school. This paper is a study protocol of a school based cluster randomized controlled trial (RCT) evaluating two school-based interventions, namely the Dream School Program (DSP) and the Mental Health Support Team (MHST). The interventions aim to improve psychosocial learning environments and subsequently school achievements and decrease drop-out and absence. The COMPLETE RCT is aimed at youth in upper secondary school, grade 1 (age 15-16 years), and examines the effect of the combination of the DSP and the MHST; and the DSP only, compared with a comparison group on the following primary outcomes: student completion, presence, average grade, and self-reported mental health. Seventeen upper secondary schools from four counties in Norway were randomized to one of the three arms: 1) DSP and MHST; 2) DSP; and 3) comparison (offered DSP intervention in 2018/2019). The study will evaluate the interventions based on information from two cohorts of students (cohort 1 (C1) and cohort 2 (C2)). For C1, data was collected at baseline (August 2016), and at first follow-up seven months later. Second follow-up will be collected 19 months after baseline. For C2, data was collected at baseline (August 2017), and first and second follow-up will be collected similarly to that of C2 seven and 19 months respectively after baseline. Process evaluations based on focus groups, interviews and observation will be conducted twice (first completed spring 2017). The COMPLETE trial is a large study that can provide useful knowledge about what interventions might effectively improve completion of upper secondary school. Its thorough process evaluation will provide critical information about barriers and points of improvement for optimizing intervention implementation. Findings can guide school development in the perspective of improving psychosocial learning environments and subsequent completion of upper secondary schooling. The trial was retrospectively registered in the ClinicalTrials.gov register on December 22.2017: NCT03382080 .

Entacapone and prostate cancer in Parkinson's disease patients: A large Veterans Affairs healthcare system study.

PubMed

Major, Jacqueline M; Dong, Diane; Cunningham, Francesca; By, Kunthel; Hur, Kwan; Shih, David C; Jiang, Rong; Podskalny, Gerald D; Wei, XiangMing; Pinheiro, Simone; Bird, Steven T; Keeton, Stephine; Graham, David J

2018-05-05

An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting. To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis. Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via linkage to the VA cancer registry. Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the entacapone-treated group comprised 5,257 subjects. Twenty-three prostate cancer cases occurred in the entacapone cohort and ninety-seven in the control cohort. The overall incidence of prostate cancer was 1.8 per 1,000 person-years of risk. There was no difference in risk of prostate cancer between the cohorts for increased duration of entacapone intake (adjusted HR: 1.08; 95% confidence interval: 0.46-2.51 for cumulative exposure of ≥2 years). Time since starting drug therapy and cumulative dose (mg) also do not suggest a difference in prostate cancer risk between cohorts. Prolonged therapy with entacapone was not associated with increased prostate cancer incidence; however, findings suggest a higher severity of prostate cancer. Published by Elsevier Ltd.

Association between the Peroxisome proliferator-activated receptor-gamma Pro12Ala Variant and Haplotype and Pancreatic Cancer in a High-Risk Cohort of Smokers: A Pilot Study

PubMed Central

Fesinmeyer, Megan Dann; Stanford, Janet L.; Brentnall, Teresa A.; Mandelson, Margaret T.; Farin, Federico M.; Srinouanprachanh, Sengkeo; Afsharinejad, Zahra; Goodman, Gary E.; Barnett, Matt J.; Austin, Melissa A.

2010-01-01

Objectives The Pro12Ala variant in the proliferator-activated receptor-gamma (PPARG) gene has been associated with diabetes and several cancers. This pilot study tested for the association between Pro12Ala and pancreatic cancer risk in a high-risk sample of smokers. Methods A nested case-control study was conducted in 83 incident cases of pancreatic cancer and 166 matched controls originally recruited into a cohort chemoprevention study of lung cancer. Associations between Pro12Ala and pancreatic cancer risk were measured using conditional logistic regression. Results Carriers of the G allele (Ala) of the Pro12Ala variant had a borderline increased relative risk of pancreatic cancer compared to homozygous carriers of the C allele (Pro), with an odds ratio (OR) of 1.79 (95% confidence interval (CI): 0.96–3.33, p-value: 0.06). Among subjects randomized to high-dose vitamin A, the OR was 2.80 (95: CI: 1.16–6.74, p-value 0.02) versus 1.20 (95% CI: 0.45–3.23, p-value 0.71) in the placebo group. A haplotype including Pro12Ala was also significantly associated with pancreatic cancer risk in all subjects and in subjects randomized to vitamin A. Conclusions This analysis presents the first evidence that PPARG may be associated with pancreatic cancer risk, and this candidate gene should be investigated in future, larger studies. PMID:19436234

Meta-analysis of vaccine effectiveness of mumps-containing vaccine under different immunization strategies in China.

PubMed

Wang, Huaqing; Hu, Yongmei; Zhang, Guomin; Zheng, Jingshan; Li, Li; An, Zhijie

2014-08-20

To evaluate vaccine effectiveness (VE) of mumps-containing vaccine (MuV) under different immunization strategies. We conducted Medline, Embase, China National Knowledge Internet (CNKI), and Wan Fang Database (WF) searches for Chinese and English language articles describing studies of mumps VE in a Chinese population. Evaluated articles were scored on quality using the Newcastle-Ottawa Scale. Meta-analysis was conducted using random effects models. Sensitivity analysis, subgroup analysis and meta-regression were conducted to explore heterogeneity. A total of 32 studies in 19 papers were included; 14 were case-control studies, and 18 were cohort studies. Half of the studies were of high quality; 41% were of moderate quality. The overall VE for mumps containing vaccine (either one dose or two doses) was 85% (95% CI 76-90%) for cohort studies and 88% (95% CI 82-92%) for case-control studies. Using random effects meta-regression we found significant differences in some study covariates; for instance, VE varied by population (VE=88% in day care versus 69% in pupil, p=0.008) and emergency versus routine immunization (VE=80% for routine immunization versus 95% for emergency immunization, p=0.041). However, these results must be interpreted with caution due to the low number of studies in subgroups, with the permutation test giving non-significant results that indicated that the results may be due to chance. MuV provides good protection from mumps infection. Further studies of mumps VE with larger sample sizes enabling subgroup analyses will be needed to confirm our findings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE).

PubMed

Kryscio, Richard J; Abner, Erin L; Caban-Holt, Allison; Lovell, Mark; Goodman, Phyllis; Darke, Amy K; Yee, Monica; Crowley, John; Schmitt, Frederick A

2017-05-01

Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia. To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men. The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms. Participants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment. Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen. The mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo. Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.

Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics: HIP BMD LOSS & FRACTURE RISK MARKERS BY POPULATION-BASED SERUM PROTEOMICS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nielson, Carrie M.; Wiedrick, Jack; Shen, Jian

Accelerated bone loss significantly increases the risk of osteoporosis and fracture. The mechanisms underlying bone loss remain incompletely understood, and there are few available biomarkers. We utilized a novel proteomics approach to identify serum peptides and proteins associated with bone loss in 1967 older men who were randomly chosen from the Osteoporotic Fracture in Men Study (MrOS study) (age ≥ 65 yrs). Men had 2-3 measures of femoral neck BMD over an average follow-up of 4.6 years. Change in BMD was estimated and then categorized into three groups: maintained BMD (n=453), expected loss (n=1185) and accelerated loss (n=237). A liquidmore » chromatography–ion mobility separation-mass spectrometry (LC-IMS-MS) proteomics platform was used to identify and quantify peptides from serum proteins. The whole cohort was randomly divided into discovery (N= 960) and validation (N= 915) sub-cohorts. Linear regression models and a random forest approach were used to discover differentially abundant individual peptides and a proteomic signature that distinguished individuals with accelerated bone loss from those who maintained BMD. Network analyses were performed using the MetaCore knowledgebase. We identified 12 peptides that were associated with BMD loss in both discovery (P< 0.1 FDR) and replication sub-cohorts (P<0.05). Those 12 peptides mapped to the following proteins: ALS, LYVE1, RNAS1, C2, ICOSL, C163A, C7, HEMO, CD14, CERU, CRAC1 and CD59. Meta-analysis of peptidesassociated with bone loss identified 6 additional proteins including GRP78, IGF-2, SHBG, ENPP2, IBP2 and IBP6. We also identified a proteomic signature that was predictive of BMD loss with a discriminative value similar to serum bone marker carboxy-terminal collagen crosslink peptide (CTX). Interestingly, combining the proteomic signature with CTX significantly improved the ability to discriminate men with accelerated loss. In summary, we have identified potential new biomarkers for bone loss that provide a more in depth understanding of its pathophysiology.« less

Dietary patterns in obese pregnant women; influence of a behavioral intervention of diet and physical activity in the UPBEAT randomized controlled trial.

PubMed

Flynn, Angela C; Seed, Paul T; Patel, Nashita; Barr, Suzanne; Bell, Ruth; Briley, Annette L; Godfrey, Keith M; Nelson, Scott M; Oteng-Ntim, Eugene; Robinson, Sian M; Sanders, Thomas A; Sattar, Naveed; Wardle, Jane; Poston, Lucilla; Goff, Louise M

2016-11-29

Understanding dietary patterns in obese pregnant women will inform future intervention strategies to improve pregnancy outcomes and the health of the child. The aim of this study was to investigate the effect of a behavioral intervention of diet and physical activity advice on dietary patterns in obese pregnant woman participating in the UPBEAT study, and to explore associations of dietary patterns with pregnancy outcomes. In the UPBEAT randomized controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city populations were randomly assigned to receive a diet/physical activity intervention or standard antenatal care. The dietary intervention aimed to reduce glycemic load and saturated fat intake. Diet was assessed using a food frequency questionnaire (FFQ) at baseline (15 +0 -18 +6 weeks' gestation), post intervention (27 +0 -28 +6 weeks) and in late pregnancy (34 +0 -36 +0 weeks). Dietary patterns were characterized using factor analysis of the baseline FFQ data, and changes compared in the control and intervention arms. Patterns were related to pregnancy outcomes in the combined control/intervention cohort (n = 1023). Four distinct baseline dietary patterns were defined; Fruit and vegetables, African/Caribbean, Processed, and Snacks, which were differently associated with social and demographic factors. The UPBEAT intervention significantly reduced the Processed (-0.14; 95% CI -0.19, -0.08, P <0.0001) and Snacks (-0.24; 95% CI -0.31, -0.17, P <0.0001) pattern scores. In the adjusted model, baseline scores for the African/Caribbean (quartile 4 compared with quartile 1: OR = 2.46; 95% CI 1.41, 4.30) and Processed (quartile 4 compared with quartile 1: OR = 2.05; 95% CI 1.23, 3.41) patterns in the entire cohort were associated with increased risk of gestational diabetes. In a diverse cohort of obese pregnant women an intensive dietary intervention improved Processed and Snack dietary pattern scores. African/Caribbean and Processed patterns were associated with an increased risk of gestational diabetes, and provide potential targets for future interventions. Current controlled trials; ISRCTN89971375.

Real-world Canagliflozin Utilization: Glycemic Control Among Patients With Type 2 Diabetes Mellitus-A Multi-Database Synthesis.

PubMed

Chow, Wing; Miyasato, Gavin; Kokkotos, Fotios K; Bailey, Robert A; Buysman, Erin K; Henk, Henry J

2016-09-01

Randomized controlled trials have found that treatment of type 2 diabetes mellitus with canagliflozin, a sodium glucose co-transporter 2 inhibitor, is associated with significant reductions in glycosylated hemoglobin (HbA1c) levels. However, very few studies have evaluated the effectiveness of sodium glucose co-transporter 2 inhibitors in a real-world context. This data synthesis aims to examine the demographic characteristics and glycemic control among patients treated with canagliflozin in clinical practice, using results obtained from 2 US-specific retrospective administrative claims databases. Data included in the synthesis were derived from 2 large claims databases (the Optum Research Database and the Inovalon MORE(2) Registry, Research Edition) and were obtained from 3 recently published retrospective observational studies of adult patients with type 2 diabetes mellitus who were treated with canagliflozin. Two of the studies used the Optum database (3-month and 6-month follow-up) and 1 study used the Inovalon database (mean follow-up of 4 months). Patient demographic characteristics, clinical characteristics, treatment utilization, and achievement of glycemic goals at baseline and after canagliflozin treatment were evaluated across the 3 studies. Results were assessed using univariate descriptive statistics. Baseline demographic characteristics were generally similar between the Optum and Inovalon cohorts. Mean baseline HbA1c was 8.7% in the Optum and 8.3% in the Inovalon cohort. Seventy-five percent of the Optum (3-month study) cohort and 74% of the Inovalon cohort used 2 or more antihyperglycemic agents. During follow-up, in both cohorts, the proportion of patients who achieved tight glycemic control (HbA1c <7.0%) more than doubled, while the proportion who had poor control (HbA1c ≥9.0%) decreased by approximately 50%. Among patients who had baseline HbA1c ≥7.0%, 21% of the Optum cohort and 24% of the Inovalon cohort achieved tight glycemic control (HbA1c <7.0%), and the proportion of patients achieving HbA1c <8.0% more than doubled in both cohorts (from 30% to 61% in the Optum cohort, and from 33% to 69% in the Inovalon cohort). This synthesis of real-world data from 2 large patient databases suggests that treatment of type 2 diabetes mellitus with canagliflozin is associated with significant and consistent improvements in glycemic control. Patients with varying HbA1c control and multiple antihyperglycemic agent use were able to lower their HbA1c levels with canagliflozin treatment. Additional studies with longer follow-up would be beneficial to evaluate the durability of the real-world effectiveness of canagliflozin. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

A Phase I, Randomised, First-in-Human Study of an Antisense Oligonucleotide Directed Against SOD1 Delivered Intrathecally in SOD1-Familial ALS Patients

PubMed Central

Miller, Timothy; Pestronk, Alan; David, William; Rothstein, Jeffrey; Simpson, Ericka; Appel, Stanley H.; Andres, Patricia L.; Mahoney, Katy; Allred, Peggy; Alexander, Katie; Ostrow, Lyle W.; Schoenfeld, David; Macklin, Eric A.; Norris, Daniel A.; Manousakis, Georgios; Crisp, Matthew; Smith, Richard; Bennett, C.F.; Bishop, Kathie; Cudkowicz, Merit E

2013-01-01

Objective To evaluate the safety, tolerability, and pharmacokinetics of an antisense oligonucleotide designed to inhibit SOD1 expression (ISIS 333611) following intrathecal administration in patients with SOD1-related familial amyotrophic lateral sclerosis (ALS). Background Mutations in SOD1 cause 13% of familial ALS. In animal studies, ISIS 333611 delivered to the cerebrospinal fluid (CSF) distributed to the brain and spinal cord, decreased SOD1 mRNA and protein levels in spinal cord tissue, and prolonged survival in the SOD1G93A rat ALS model. Methods In a randomized, placebo controlled Phase 1 trial, ISIS 333611 was delivered by intrathecal infusion using an external pump over 11.5 hours at increasing doses to four cohorts of eight SOD1 positive ALS subjects (randomized 6 drug: 2 placebo/cohort). Subjects were allowed to re-enroll in subsequent cohorts. Safety and tolerability assessments were made during the infusion and periodically over 28 days following the infusion. CSF and plasma drug levels were measured. Findings No dose-limiting toxicities were identified at doses up to 3.0 mg. No safety or tolerability concerns related to ISIS 333611 were identified. There were no serious adverse events (AEs) in ISIS 333611-treated subjects. Re-enrollment and re-dosing of subjects with ISIS 333611 was also well tolerated. Dose-dependent CSF and plasma concentrations were observed. Interpretation In this first clinical study to report intrathecal delivery of an antisense oligonucleotide, ISIS 333611 was well tolerated when administered as an intrathecal infusion in subjects with SOD1 familial ALS. CSF and plasma drug levels were consistent with levels predicted from preclinical studies. These results suggest that antisense oligonucleotide delivery to the central nervous system may be a feasible therapeutic strategy for neurological disorders. Source of funding ALS Association, Muscular Dystrophy Association, Isis Pharmaceuticals PMID:23541756

Aspirin as a potential modality for the chemoprevention of breast cancer: A dose-response meta-analysis of cohort studies from 857,831 participants

PubMed Central

Lu, Liming; Shi, Leiyu; Zeng, Jingchun; Wen, Zehuai

2017-01-01

Background Previous meta-analyses on the relationship between aspirin use and breast cancer risk have drawn inconsistent results. In addition, the threshold effect of different doses, frequencies and durations of aspirin use in preventing breast cancer have yet to be established. Results The search yielded 13 prospective cohort studies (N=857,831 participants) that reported an average of 7.6 cases/1,000 person-years of breast cancer during a follow-up period of from 4.4 to 14 years. With a random effects model, a borderline significant inverse association was observed between overall aspirin use and breast cancer risk, with a summarized RR = 0.94 (P = 0.051, 95% CI 0.87-1.01). The linear regression model was a better fit for the dose-response relationship, which displayed a potential relationship between the frequency of aspirin use and breast cancer risk (RR = 0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It was also a better fit for the duration of aspirin use and breast cancer risk (RR = 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use). Methods We searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for relevant prospective cohort studies of aspirin use and breast cancer risk. Meta-analysis of relative risks (RR) estimates associated with aspirin intake were presented by fixed or random effects models. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Conclusion Our study confirmed a dose-response relationship between aspirin use and breast cancer risk. For clinical prevention, long term (>5 years) consistent use (2-7 times/week) of aspirin appears to be more effective in achieving a protective effect against breast cancer. PMID:28418881

Aspirin as a potential modality for the chemoprevention of breast cancer: A dose-response meta-analysis of cohort studies from 857,831 participants.

PubMed

Lu, Liming; Shi, Leiyu; Zeng, Jingchun; Wen, Zehuai

2017-06-20

Previous meta-analyses on the relationship between aspirin use and breast cancer risk have drawn inconsistent results. In addition, the threshold effect of different doses, frequencies and durations of aspirin use in preventing breast cancer have yet to be established. The search yielded 13 prospective cohort studies (N=857,831 participants) that reported an average of 7.6 cases/1,000 person-years of breast cancer during a follow-up period of from 4.4 to 14 years. With a random effects model, a borderline significant inverse association was observed between overall aspirin use and breast cancer risk, with a summarized RR = 0.94 (P = 0.051, 95% CI 0.87-1.01). The linear regression model was a better fit for the dose-response relationship, which displayed a potential relationship between the frequency of aspirin use and breast cancer risk (RR = 0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It was also a better fit for the duration of aspirin use and breast cancer risk (RR = 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use). We searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for relevant prospective cohort studies of aspirin use and breast cancer risk. Meta-analysis of relative risks (RR) estimates associated with aspirin intake were presented by fixed or random effects models. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Our study confirmed a dose-response relationship between aspirin use and breast cancer risk. For clinical prevention, long term (>5 years) consistent use (2-7 times/week) of aspirin appears to be more effective in achieving a protective effect against breast cancer.

Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients

NASA Astrophysics Data System (ADS)

Tang, Jie; Liu, Rong; Zhang, Yue-Li; Liu, Mou-Ze; Hu, Yong-Fang; Shao, Ming-Jie; Zhu, Li-Jun; Xin, Hua-Wen; Feng, Gui-Wen; Shang, Wen-Jun; Meng, Xiang-Guang; Zhang, Li-Rong; Ming, Ying-Zi; Zhang, Wei

2017-02-01

Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the “derivation cohort” to develop dose-prediction algorithm, while the remaining 20% constituted the “validation cohort” to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

Telephone vs. mail survey gives different SF-36 quality-of-life scores among cancer survivors.

PubMed

Buskirk, Trent D; Stein, Kevin D

2008-10-01

To assess whether SF-36 quality-of-life (QOL) subscale scores varied across two survey modes controlling for cancer type and diagnosis cohort. Stratified random samples of 720 cancer survivors from six cancer types and three time-since diagnosis cohorts were selected from two state cancer registries. Selected survivors were randomly assigned to mail, telephone, or choice of these for survey administration. This study analyzes completed questionnaires obtained from 140 and 155 survivors who were assigned to telephone and mail, respectively. A significant multivariate effect for survey mode was noted. Mean levels for each subscale controlling for age and accounting for cancer type were higher for telephone compared to mail respondents; significant differences were noted for vitality, role physical, and mental health. The impact of cancer type on QOL subscales was not significant, and the effect of mode was consistent across cancer type. Previous findings in mode effects for the SF-36 are reproduced here among cancer survivors who may feel more comfortable revealing physical and emotional deficits via mail rather than by telephone. For cancer survivors, it may be that "social desirability" favors responses implying more functioning be it perceived, mental, or physical.

Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers.

PubMed

Lenters, Virissa; Basinas, Ioannis; Beane-Freeman, Laura; Boffetta, Paolo; Checkoway, Harvey; Coggon, David; Portengen, Lützen; Sim, Malcolm; Wouters, Inge M; Heederik, Dick; Vermeulen, Roel

2010-04-01

To examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins. Risk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case-cohort, and 2 case-control studies of cotton textile industry workers, and 15 cohort and 2 case-control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses. The summary risk of lung cancer was 0.72 (95% CI, 0.57-0.90) for textile workers and 0.62 (0.52-0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose-dependent protective effect of endotoxins on lung cancer risk. Despite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer.

Patient Decision Aids Improve Decision Quality and Patient Experience and Reduce Surgical Rates in Routine Orthopaedic Care: A Prospective Cohort Study.

PubMed

Sepucha, Karen; Atlas, Steven J; Chang, Yuchiao; Dorrwachter, Janet; Freiberg, Andrew; Mangla, Mahima; Rubash, Harry E; Simmons, Leigh H; Cha, Thomas

2017-08-02

Patient decision aids are effective in randomized controlled trials, yet little is known about their impact in routine care. The purpose of this study was to examine whether decision aids increase shared decision-making when used in routine care. A prospective study was designed to evaluate the impact of a quality improvement project to increase the use of decision aids for patients with hip or knee osteoarthritis, lumbar disc herniation, or lumbar spinal stenosis. A usual care cohort was enrolled before the quality improvement project and an intervention cohort was enrolled after the project. Participants were surveyed 1 week after a specialist visit, and surgical status was collected at 6 months. Regression analyses adjusted for clustering of patients within clinicians and examined the impact on knowledge, patient reports of shared decision-making in the visit, and surgical rates. With 550 surveys, the study had 80% to 90% power to detect a difference in these key outcomes. The response rates to the 1-week survey were 70.6% (324 of 459) for the usual care cohort and 70.2% (328 of 467) for the intervention cohort. There was no significant difference (p > 0.05) in any patient characteristic between the 2 cohorts. More patients received decision aids in the intervention cohort at 63.6% compared with the usual care cohort at 27.3% (p = 0.007). Decision aid use was associated with higher knowledge scores, with a mean difference of 18.7 points (95% confidence interval [CI], 11.4 to 26.1 points; p < 0.001) for the usual care cohort and 15.3 points (95% CI, 7.5 to 23.0 points; p = 0.002) for the intervention cohort. Patients reported more shared decision-making (p = 0.009) in the visit with their surgeon in the intervention cohort, with a mean Shared Decision-Making Process score (and standard deviation) of 66.9 ± 27.5 points, compared with the usual care cohort at 62.5 ± 28.6 points. The majority of patients received their preferred treatment, and this did not differ by cohort or decision aid use. Surgical rates were lower in the intervention cohort for those who received the decision aids at 42.3% compared with 58.8% for those who did not receive decision aids (p = 0.023) and in the usual care cohort at 44.3% for those who received decision aids compared with 55.7% for those who did not receive them (p = 0.45). The quality improvement project successfully integrated patient decision aids into a busy orthopaedic clinic. When used in routine care, decision aids are associated with increased knowledge, more shared decision-making, and lower surgical rates. There is increasing pressure to design systems of care that inform and involve patients in decisions about elective surgery. In this study, the authors found that patient decision aids, when used as part of routine orthopaedic care, were associated with increased knowledge, more shared decision-making, higher patient experience ratings, and lower surgical rates.

The Perils of Ignoring Design Effects in Experimental Studies: Lessons from a Mammography Screening Trial

PubMed Central

Glenn, Beth A.; Bastani, Roshan; Maxwell, Annette E.

2013-01-01

Objective Threats to external validity including pretest sensitization and the interaction of selection and an intervention are frequently overlooked by researchers despite their potential to significantly influence study outcomes. The purpose of this investigation was to conduct secondary data analyses to assess the presence of external validity threats in the setting of a randomized trial designed to promote mammography use in a high risk sample of women. Design During the trial, recruitment and intervention implementation took place in three cohorts (with different ethnic composition), utilizing two different designs (pretest-posttest control group design; posttest only control group design). Results Results reveal that the intervention produced different outcomes across cohorts, dependent upon the research design used and the characteristics of the sample. Conclusion These results illustrate the importance of weighing the pros and cons of potential research designs before making a selection and attending more closely to issues of external validity. PMID:23289517

Effect of Ginkgo biloba on visual field and contrast sensitivity in Chinese patients with normal tension glaucoma: a randomized, crossover clinical trial.

PubMed

Guo, Xinxing; Kong, Xiangbin; Huang, Rui; Jin, Ling; Ding, Xiaohu; He, Mingguang; Liu, Xing; Patel, Mehul Chimanlal; Congdon, Nathan G

2014-01-07

We evaluated the effect of ginkgo biloba extract on visual field defect and contrast sensitivity in a Chinese cohort with normal tension glaucoma. In this prospective, randomized, placebo-controlled crossover study, patients newly diagnosed with normal tension glaucoma, either in a tertiary glaucoma clinic (n = 5) or in a cohort undergoing routine general physical examinations in a primary care clinic (n = 30), underwent two 4-week phases of treatment, separated by a washout period of 8 weeks. Randomization determined whether ginkgo biloba extract (40 mg, 3 times per day) or placebo (identical-appearing tablets) was received first. Primary outcomes were change in contrast sensitivity and mean deviation on 24-2 SITA standard visual field testing, while secondary outcomes included IOP and self-reported adverse events. A total of 35 patients with mean age 63.7 (6.5) years were randomized to the ginkgo biloba extract-placebo (n = 18) or the placebo-ginkgo biloba extract (n = 17) sequence. A total of 28 patients (80.0%, 14 in each group) who completed testing did not differ at baseline in age, sex, visual field mean deviation, contrast sensitivity, IOP, or blood pressure. Changes in visual field and contrast sensitivity did not differ by treatment received or sequence (P > 0.2 for all). Power to have detected a difference in mean defect as large as previously reported was 80%. In contrast to some previous reports, ginkgo biloba extract treatment had no effect on mean defect or contrast sensitivity in this group of normal tension glaucoma patients. (http://www.chictr.org number, ChiCTR-TRC-08000724).

A retrospective cohort study on the association between periapical abscess, advanced periodontal disease, and the national oral health screening program among Korean adults.

PubMed

Ha, Jung-Eun; Jung, Se-Hwan; Jin, Bo-Hyoung; Lee, Byoung-Jin; Bae, Kwang-Hak

2013-09-01

The National Oral Health Screening Program (NOHSP) is a general population-based program in Korea. The objective of this study was to assess the association between participation in the NOHSP and dental visit for periapical abscess (PA) and advanced periodontal disease (APD) among Korean adults. Data were obtained for subjects from the National Health Insurance database. The authors conducted a retrospective cohort study of 9358 randomly selected subjects who were between 40 and 64 years old in 2002. The outcomes of dental visit for PA or APD from the years 2003 to 2007 were compared between the screening and nonscreening groups. The nonscreening group had 19% higher risk of PA and 15% higher risk of APD. This study suggests that the NOHSP may decrease the risk of dental visit because of PA and APD by preventing the progress of lesion to the advanced stage among Korean adults.

Understanding long-term protection of human papillomavirus vaccination against cervical carcinoma: Cancer registry-based follow-up.

PubMed

Rana, Muhammad Mohsin; Huhtala, Heini; Apter, Dan; Eriksson, Tiina; Luostarinen, Tapio; Natunen, Kari; Paavonen, Jorma; Pukkala, Eero; Lehtinen, Matti

2013-06-15

Phase III clinical trials of human papilloma virus (HPV) vaccination have shown ≥95% efficacy against HPV16/18 associated cervical intraepithelial neoplasia (CIN) Grade 2/3. Long-term surveillance is, however, needed to determine the overall vaccine efficacy (VE) against CIN3 and invasive cervical carcinoma (ICC). During population-based recruitment between September 2002 and March 2003, 1,749 16- to 17-year old Finns participated in a multi-national randomized Phase III HPV6/11/16/18 vaccine (FUTURE II) trial for the determination of VE against HPV16/18 positive CIN2/3. The passive follow-up started at the country-wide, population-based Finnish Cancer Registry (FCR) six months after the active follow-up and voluntary cross-vaccination in April 2007. A cluster randomized, population-based reference cohort of 15,744 unvaccinated, originally 18-19 year old Finns was established in two phases in 2003 and 2005 after the FUTURE II recruitment. We linked these cohorts with the FCR in 2007-2011 (HPV vaccine and placebo cohorts) and 2006-2010 and 2008-2012 (unvaccinated reference cohorts 1 and 2) to compare their incidences of CIN3 and ICC. The four years passive follow-up resulted in 3,464, 3,444 and 62,876 person years for the HPV6/11/16/18, original placebo and reference cohorts, after excluding cases discovered during the clinical follow-up and individuals not at risk. The numbers of CIN3 and ICC cases identified were 0 and 0, 3 and 0, 59 and 3 for the HPV6/11/16/18, placebo and the unvaccinated reference cohorts. The corresponding CIN3 incidence rates were 0/100,000 (95% confidence interval 0.0-106.5), 87.1/100,000 (95% CI 17.9-254.5) and 93.8/100,000 (95% CI 71.4-121), respectively. Long-term surveillance up to 8 years (and longer) post vaccination of the HPV6/11/16/18 vaccine and placebo cohorts, and the unvaccinated reference cohort (not exposed to interventions) for the most stringent efficacy end-points by passive cancer registry-based follow-up is feasible. Copyright © 2012 UICC.

Risk of acute myocardial infarction in upper tract urothelial carcinoma patients receiving radical nephroureterectomy: a population-based cohort study

PubMed Central

Lin, Shih-Yi; Lin, Cheng-Li; Chang, Chao-Hsiang; Wu, His-Chin; Wang, I-Kuan; Chou, Che-Yi; Liang, Ji-An

2017-01-01

Background The outcomes of upper tract urothelial carcinoma (UTUC) receiving radical nephroureterectomy were usually limited to small sample size, case-control studies, and often focused on cancer progression. Risk of acute myocardial infarction (AMI) in these patients was never investigated. Results The overall incidences of AMI were 3.39, 1.44, and 1.70 per 10,000 person-years in the radical nephroureterectomy, nonnephroureterectomy, and non-UTUC cohorts, respectively. Multivariable Cox proportional hazard regression analysis revealed a significantly higher AMI risk in the radical nephroureterectomy cohort [adjusted HR (aHR) = 1.83, 95% confidence interval (CI) = 1.08–3.11], compared with non-UTUC cohorts. The risk of mortality were the highest in patients with UTUC who had undergone radical nephroureterectomy [adjusted HR (aHR) = 5.37, 95% confidence interval (CI) = 4.80–6.02]. Materials and Methods From the Taiwan National Health Insurance claims data, 1,359 patients with UTUC who had undergone radical nephroureterectomy and 3,154 patients with UTUC who had undergone nephron sparing surgery and were newly diagnosed between 2000 and 2010 were identified. For each patient, 4 individuals without UTUC were randomly selected and frequency matched by age, sex, and diagnosis year. Conclusions Patients with UTUC who have undergone radical nephroureterectomy are at a higher risk of developing AMI, compared with those receiving nephron sparing surgery. PMID:29108329

Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort.

PubMed

Escalas, Cécile; Dalichampt, Marie; Dougados, Maxime; Poiraudeau, Serge

2016-03-01

To evaluate the effect of physiotherapy on functional limitation in an observational cohort of early axial spondyloarthritis. prospective population-based cohort study. 708 patients with early axial spondyloarthritis between 2007 and 2010 naive of TNF blockers. early physiotherapy defined by at least eight supervised sessions of physical therapy during the first six months. the primary outcome was functional improvement defined by a relative improvement of at least 20% in BASFI at six months. Secondary outcomes were improvement in BASFI at one and two years and ASAS20 response criteria at six months. a propensity score of having physiotherapy was developed and multivariate analysis using propensity score weighting were used to assess the effect of physiotherapy on outcome. Overall, 166 (24%) patients had physiotherapy during the first six months. After using propensity score weighting, there was no functional improvement on the primary outcome in patients treated with early physical therapy (relative risk [IC95%]: 1.15 [0.91-1.45]). No differences were observed on secondary outcomes (relative risk [IC95%]: 0.94 [0.80-1.11]). It seems there is no functional benefit for patients with early spondyloarthritis to be treated early by physiotherapy in daily practice, even though the efficacy of physiotherapy has been shown in several randomized controlled studies. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Coffee, caffeine, and risk of completed suicide: results from three prospective cohorts of American adults.

PubMed

Lucas, Michel; O'Reilly, Eilis J; Pan, An; Mirzaei, Fariba; Willett, Walter C; Okereke, Olivia I; Ascherio, Alberto

2014-07-01

To evaluate the association between coffee and caffeine consumption and suicide risk in three large-scale cohorts of US men and women. We accessed data of 43,599 men enrolled in the Health Professionals Follow-up Study (HPFS, 1988-2008), 73,820 women in the Nurses' Health Study (NHS, 1992-2008), and 91,005 women in the NHS II (1993-2007). Consumption of caffeine, coffee, and decaffeinated coffee, was assessed every 4 years by validated food-frequency questionnaires. Deaths from suicide were determined by physician review of death certificates. Multivariate adjusted relative risks (RRs) were estimated with Cox proportional hazard models. Cohort specific RRs were pooled using random-effect models. We documented 277 deaths from suicide. Compared to those consuming ≤ 1 cup/week of caffeinated coffee (< 8 oz/237 ml), the pooled multivariate RR (95% confidence interval [CI]) of suicide was 0.55 (0.38-0.78) for those consuming 2-3 cups/day and 0.47 (0.27-0.81) for those consuming ≥ 4 cups/day (P trend < 0.001). The pooled multivariate RR (95% CI) for suicide was 0.75 (0.63-0.90) for each increment of 2 cups/day of caffeinated coffee and 0.77 (0.63-0.93) for each increment of 300 mg/day of caffeine. These results from three large cohorts support an association between caffeine consumption and lower risk of suicide.

Clinical and Demographic Profile of Patients Receiving Fingolimod in Clinical Practice in Germany and the Benefit-Risk Profile of Fingolimod After 1 Year of Treatment: Initial Results From the Observational, Noninterventional Study PANGAEA.

PubMed

Ziemssen, Tjalf; Lang, Michael; Tackenberg, Björn; Schmidt, Stephan; Albrecht, Holger; Klotz, Luisa; Haas, Judith; Lassek, Christoph; Medin, Jennie; Cornelissen, Christian

2018-01-01

The population with multiple sclerosis receiving treatment in clinical practice differs from that in randomized controlled trials (RCTs). An assessment of the real-world benefit-risk profile of therapies is needed. This analysis used data from the large, noninterventional, observational German study Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) to assess prospectively baseline characteristics and outcomes after 12 months (± 90 days) of fingolimod treatment. Patients were divided into 2 cohorts: fingolimod starter [first received fingolimod in PANGAEA (n = 3315)] and previous study [received fingolimod before enrollment in PANGAEA in RCTs (n = 875), some of whom also had baseline data at entry into RCTs (n = 505)]. At PANGAEA baseline, patients in the fingolimod starter versus the previous study cohort had a higher annualized relapse rate [ARR (95% confidence interval): 1.79 (1.75-1.83) vs 1.32 (1.25-1.40)] and Expanded Disability Status Scale score [3.11 (3.04-3.17) vs 2.55 (2.44-2.66)]. A greater proportion in the fingolimod starter versus previous study cohort had diabetes (2.0% vs 0.7%). After 12 months of fingolimod, ARRs were lower than in the 12 months before PANGAEA enrollment in the fingolimod starter [0.386 (0.360-0.414)] and previous study [0.276 (0.238-0.320)] cohorts. Expanded Disability Status Scale scores were stable versus baseline. Adverse events were experienced by similar proportions in both cohorts during fingolimod treatment. Relevant differences exist in disease activity and comorbidities between patients receiving fingolimod in clinical practice versus RCTs. Irrespective of baseline differences indicating a higher proportion at an advanced stage of multiple sclerosis in the real world versus RCTs, fingolimod remains effective, with a manageable safety profile.

Racial disparities in self-rated health: Trends, explanatory factors, and the changing role of socio-demographics

PubMed Central

Beck, Audrey N.; Finch, Brian K.; Lin, Shih-Fan; Hummer, Robert A.; Masters, Ryan K.

2014-01-01

This paper uses data from the U.S. National Health Interview Surveys (N = 1,513,097) to describe and explain temporal patterns in black-white health disparities with models that simultaneously consider the unique effects of age, period, and cohort. First, we employ cross-classified random effects age–period–cohort (APC) models to document black-white disparities in self-rated health across temporal dimensions. Second, we use decomposition techniques to shed light on the extent to which socio-economic shifts in cohort composition explain the age and period adjusted racial health disparities across successive birth cohorts. Third, we examine the extent to which exogenous conditions at the time of birth help explain the racial disparities across successive cohorts. Results show that black-white disparities are wider among the pre-1935 cohorts for women, falling thereafter; disparities for men exhibit a similar pattern but exhibit narrowing among cohorts born earlier in the century. Differences in socioeconomic composition consistently contribute to racial health disparities across cohorts; notably, marital status differences by race emerge as an increasingly important explanatory factor in more recent cohorts for women whereas employment differences by race emerge as increasingly salient in more recent cohorts for men. Finally, our cohort characteristics models suggest that cohort economic conditions at the time of birth (percent large family, farm or Southern birth) help explain racial disparities in health for both men and women. PMID:24581075

Prediction of five-year all-cause mortality in Chinese patients with type 2 diabetes mellitus - A population-based retrospective cohort study.

PubMed

Wan, Eric Yuk Fai; Fong, Daniel Yee Tak; Fung, Colman Siu Cheung; Yu, Esther Yee Tak; Chin, Weng Yee; Chan, Anca Ka Chun; Lam, Cindy Lo Kuen

2017-06-01

This study aimed to develop and validate an all-cause mortality risk prediction model for Chinese primary care patients with type 2 diabetes mellitus(T2DM) in Hong Kong. A population-based retrospective cohort study was conducted on 132,462 Chinese patients who had received public primary care services during 2010. Each gender sample was randomly split on a 2:1 basis into derivation and validation cohorts and was followed-up for a median period of 5years. Gender-specific mortality risk prediction models showing the interaction effect between predictors and age were derived using Cox proportional hazards regression with forward stepwise approach. Developed models were compared with pre-existing models by Harrell's C-statistic and calibration plot using validation cohort. Common predictors of increased mortality risk in both genders included: age; smoking habit; diabetes duration; use of anti-hypertensive agents, insulin and lipid-lowering drugs; body mass index; hemoglobin A1c; systolic blood pressure(BP); total cholesterol to high-density lipoprotein-cholesterol ratio; urine albumin to creatinine ratio(urine ACR); and estimated glomerular filtration rate(eGFR). Prediction models showed better discrimination with Harrell"'s C-statistics of 0.768(males) and 0.782(females) and calibration power from the plots than previously established models. Our newly developed gender-specific models provide a more accurate predicted 5-year mortality risk for Chinese diabetic patients than other established models. Copyright © 2017 Elsevier Inc. All rights reserved.

Causes of death and expected years of life lost among treated opioid-dependent individuals in the United States and Taiwan

PubMed Central

Chang, Kun-Chia; Wang, Jung-Der; Saxon, Andrew; Matthews, Abigail G.; Woody, George; Hser, Yih-Ing

2017-01-01

Aims This study compared the cause-specific standardized mortality ratios (SMRs) and expected years of life lost (EYLL) among opioid-dependent individuals in the United States and Taiwan. Methods Survival data came from two cohorts followed until 2014: The U.S. data were based on a randomized trial of 1,267 opioid-dependent participants enrolled between 2006 and 2009; the Taiwan data were from a study of 983 individuals that began in 2006, when opioid agonist treatment (OAT) was implemented in Taiwan. SMRs were calculated for each national cohort and compared. Kaplan-Meier estimation was performed on the survival data, then lifespans were extrapolated to 70 years (840 months) to estimate life expectancy using a semi-parametric method. EYLLs for both cohorts were estimated by subtracting their life expectancies from the age- and gender-matched referents within the general population of their respective country. Results Compared with age- and gender- matched referents, the SMRs were 3.2 for the U.S. sample and 7.8 for the Taiwan sample; the EYLLs were 7.7 and 16.4 years, respectively. Half of decedents died of unnatural causes in both cohorts; overdose deaths predominated in the U.S. and suicide in Taiwan. Conclusions Our study identified differences by country in EYLL and causes of deaths. These findings suggest that intervention strategies to reduce mortality risk by overdose (particularly in the U.S.) and suicide (particularly in Taiwan) are urgently needed in these countries. PMID:28160734

Alcohol use disorder increases the risk of necrotizing fasciitis

PubMed Central

Yii, Yong-Cheng; Hsieh, Vivian Chia-Rong; Lin, Cheng-Li; Wang, Yu-Chiao; Chen, Wei-Kung

2017-01-01

Abstract This nationwide retrospective cohort study determined the association between alcohol use disorder (AUD) and the risk of necrotizing fasciitis (NF). This study used health insurance claims data of 52,212 in-patients with AUD and 208,848 controls randomly frequency-matched by age and sex at a 1:4 ratio. The AUD cohort included patients newly diagnosed with AUD between January 1, 2000 and December 31, 2008. The NF event occurrence was observed until December 31, 2011. We used the Kaplan–Meier method to present the cumulative incidence curve and Cox proportional hazard models to depict the risk of NF in patients with AUD. The incidence of NF was 19.4 per 10,000 person-years in the AUD cohort, which was nearly 7.73-fold higher than that in the comparison cohort (2.54 per 10,000 person-years). After adjustment for age, sex, and comorbidities, the patients with AUD exhibited a 3.55-fold higher risk of NF than did the controls (hazard ratio [HR] = 3.55, 95% confidence interval [CI] = 3.00–4.20). Nevertheless, in the AUD groups without any comorbidity, patients with AUD exhibited a significant 15.2-fold higher risk of NF than did the comparison cohort (HR = 15.2, 95% CI = 10.9–21.3). Moreover, the adjusted HRs of NF risk with respect to the severity of AUD were 2.15 (95% CI = 1.76–2.62), 4.54 (95% CI = 3.67–5.62), and 10.7 (95% CI = 8.66–13.2) for mild, moderate, and severe AUD, respectively. This study indicated that AUD should be considered an independent and significant risk factor for NF. PMID:28796035

Increased risk of deep vein thrombosis and pulmonary thromboembolism in patients with organophosphate intoxication: a nationwide prospective cohort study.

PubMed

Lim, Yun-Ping; Lin, Cheng-Li; Hung, Dong-Zong; Ma, Wei-Chih; Lin, Yen-Ning; Kao, Chia-Hung

2015-01-01

Organophosphate (OP) poisoning is a critical cause of morbidity and mortality worldwide. We conducted a nationwide longitudinal cohort study to investigate the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) among patients admitted with OP intoxication.We identified patients with OP intoxication by using the Taiwan National Health Insurance Research Database and enrolled 9223 patients who were hospitalized for OP intoxication between 2000 and 2011. OP intoxication was diagnosed based on a clinical assessment and serum acetylcholinesterase levels at the time of hospital admission. Each patient in the OP intoxication cohort was randomly frequency matched with 4 patients without OP intoxication based on their age, sex, and index year (36,892 patients as control cohort), and all patients were observed from the index date until the appearance of a DVT or a PTE event, or until December 31, 2011. We analyzed the risks of DVT and PTE by using Cox proportional hazards regression models that included the demographic variables of sex, age, and comorbidities (eg, hypertension, diabetes, cerebral vascular disease, heart failure, all cancer types, and lower leg fracture or surgery).The results revealed a significantly increased risk of developing DVT among patients with OP poisoning (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.03-2.34) but not PTE (adjusted HR = 1.44; 95% CI = 0.83-2.52). Among the patients without comorbidities, the OP poisoning patients compared with controls had a higher adjusted HR of 2.12 (95% CI = 1.21-3.71) for DVT.The results of this nationwide cohort study indicate that the risk of developing DVT is markedly higher in patients with OP intoxication compared with that of the general population.

Longitudinal associations between different dementia diagnoses and medication use jointly accounting for dropout.

PubMed

Agogo, George O; Ramsey, Christine M; Gnjidic, Danijela; Moga, Daniela C; Allore, Heather

2018-04-18

ABSTRACTBackground:Longitudinal studies of older adults are characterized by high dropout rates, multimorbid conditions, and multiple medication use, especially proximal to death. We studied the association between multiple medication use and incident dementia diagnoses including Alzheimer's disease (AD), vascular dementia (VD), and Lewy-body dementia (LBD), simultaneously accounting for dropout. Using the National Alzheimer's Coordinating Center data with three years of follow-up, a set of covariate-adjusted models that ignore dropout was fit to complete-case data, and to the whole-cohort data. Additionally, covariate-adjusted joint models with shared random effects accounting for dropout were fit to the whole-cohort data. Multiple medication use was defined as polypharmacy (⩾ five medications), hyperpolypharmacy (⩾ ten medications), and total number of medications. Incident diagnoses were 2,032 for AD, 135 for VD, and 139 for LBD. Percentages of dropout at the end of follow-up were as follows: 71.8% for AD, 81.5% for VD, and 77.7% for LBD. The odds ratio (OR) estimate for hyperpolypharmacy among those with LBD versus AD was 2.19 (0.78, 6.15) when estimated using complete-case data and 3.00 (1.66, 5.40) using whole-cohort data. The OR reduced to 1.41 (0.76, 2.64) when estimated from the joint model accounting for dropout. The OR for polypharmacy using complete-case data differed from the estimates using whole-cohort data. The OR for dementia diagnoses on total number of medications was similar, but non-significant when estimated using complete-case data. Reasons for dropout should be investigated and appropriate statistical methods should be applied to reduce bias in longitudinal studies among high-risk dementia cohorts.

Validation of SAPS3 admission score and its customization for use in Korean intensive care unit patients: a prospective multicentre study.

PubMed

Lim, So Yeon; Koh, Shin Ok; Jeon, Kyeongman; Na, Sungwon; Lim, Chae-Man; Choi, Won-Il; Lee, Young-Joo; Kim, Seok Chan; Chon, Gyu Rak; Kim, Je Hyeong; Kim, Jae Yeol; Lim, Jaemin; Rhee, Chin Kook; Park, Sunghoon; Kim, Ho Cheol; Lee, Jin Hwa; Lee, Ji Hyun; Park, Jisook; Koh, Younsuck; Suh, Gee Young

2013-08-01

To externally validate the simplified acute physiology score 3 (SAPS3) and to customize it for use in Korean intensive care unit (ICU) patients. This is a prospective multicentre cohort study involving 22 ICUs from 15 centres throughout Korea. The study population comprised patients who were consecutively admitted to participating ICUs from 1 July 2010 to 31 January 2011. A total of 4617 patients were enrolled. ICU mortality was 14.3%, and hospital mortality was 20.6%. The patients were randomly assigned into one of two cohorts: a development (n = 2309) or validation (n = 2308) cohort. In the development cohort, the general SAPS3 had good discrimination (area under the receiver operating characteristics curve = 0.829), but poor calibration (Hosmer-Lemeshow goodness-of-fit test H = 123.06, P < 0.001, C = 118.45, P < 0.001). The Australasia SAPS3 did not improve calibration (H = 73.53, P < 0.001, C = 70.52, P < 0.001). Customization was achieved by altering the logit of the original SAPS3 equation. The new equation for Korean ICU patients was validated in the validation cohort, and demonstrated both good discrimination (area under the receiver operating characteristics curve = 0.835) and good calibration (H = 4.61, P = 0.799, C = 5.67, P = 0.684). General and regional Australasia SAPS3 admission scores showed poor calibration for use in Korean ICU patients, but the prognostic power of the SAPS3 was significantly improved by customization. Prediction models should be customized before being used to predict mortality in different regions of the world. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Association between physical activity and risk of nonalcoholic fatty liver disease: a meta-analysis.

PubMed

Qiu, Shanhu; Cai, Xue; Sun, Zilin; Li, Ling; Zügel, Martina; Steinacker, Jürgen Michael; Schumann, Uwe

2017-09-01

Increased physical activity (PA) is a key element in the management of patients with nonalcoholic fatty liver disease (NAFLD); however, its association with NAFLD risk has not been systematically assessed. This meta-analysis of observational studies was to quantify this association with dose-response analysis. Electronic databases were searched to January 2017 for studies of adults reporting the risk of NAFLD in relation to PA with cohort or case-control designs. Studies that reported sex-specific data were included as separate studies. The overall risk estimates were pooled using a random-effects model, and the dose-response analysis was conducted to shape the quantitative relationship. A total of 6 cohort studies from 5 articles with 32,657 incident NAFLD cases from 142,781 participants, and 4 case-control studies from 3 articles with 382 NAFLD cases and 302 controls were included. Compared with the lowest PA level, the highest PA level was associated with a risk reduction of NAFLD in cohort [RR (risk ratio) 0.79, 95% CI (confidence interval) 0.71-0.89] and case-control studies [OR (odds ratio) 0.43, 95% CI 0.27-0.68]. For cohort studies, both highest and moderate PA levels were superior to the light one in lowering NAFLD risk ( p for interaction = 0.006 and 0.02, respectively), and there was a log-linear dose-response association ( p for nonlinearity = 0.10) between PA and NAFLD risk [RR 0.82 (95% CI 0.73-0.91) for every 500 metabolic equivalent (MET)-minutes/week increment in PA]. Increased PA may lead to a reduced risk of NAFLD in a dose-dependent manner, and the current guideline-recommended minimum PA level that approximates to 500 MET-minutes/week is able to moderately reduce the NAFLD risk.

Associations of rotational shift work and night shift status with hypertension: a systematic review and meta-analysis.

PubMed

Manohar, Sandhya; Thongprayoon, Charat; Cheungpasitporn, Wisit; Mao, Michael A; Herrmann, Sandra M

2017-10-01

The reported risks of hypertension (HTN) in rotating shift and night shift workers are controversial. The objective of this meta-analysis was to assess the association between shift work status and HTN. A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through October 2016. Studies that reported odds ratios (OR) comparing the risk of HTN in shift workers were included. A prespecified subgroup analysis by rotating shift and night shift statuses were also performed. Pooled OR and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The protocol for this study is registered with International Prospective Register of Systematic Reviews; no. CRD42016051843. Twenty-seven observational studies (nine cohort and 18 cross-sectional studies) with a total of 394 793 individuals were enrolled. The pooled ORs of HTN in shift workers in cohort and cross-sectional studies were 1.31 (95% CI, 1.07-1.60) and 1.10 (95% CI, 1.00-1.20), respectively. When meta-analysis was restricted only to cohort studies in rotating shift, the pooled OR of HTN in rotating shift workers was 1.34 (95% CI, 1.08-1.67). The data regarding night shift and HTN in cohort studies was limited. The pooled OR of HTN in night shift workers in cross-sectional studies was 1.07 (95% CI, 0.85-1.35). Based on the findings of our meta-analysis, shiftwork status may play an important role in HTN, as there is a significant association between rotating shift work and HTN. However, there is no significant association between night shift status and risk of HTN.

Vegetarianism and breast, colorectal and prostate cancer risk: an overview and meta-analysis of cohort studies.

PubMed

Godos, J; Bella, F; Sciacca, S; Galvano, F; Grosso, G

2017-06-01

Vegetarian diets may be associated with certain benefits toward human health, although current evidence is scarce and contrasting. In the present study, a systematic review and meta-analysis of prospective cohort studies was performed with respect to the association between vegetarian diets and breast, colorectal and prostate cancer risk. Studies were systematically searched in Pubmed and EMBASE electronic databases. Eligible studies had a prospective design and compared vegetarian, semi- and pesco-vegetarian diets with a non-vegetarian diet. Random-effects models were applied to calculate relative risks (RRs) of cancer between diets. Statistical heterogeneity and publication bias were explored. A total of nine studies were included in the meta-analysis. Studies were conducted on six cohorts accounting for 686 629 individuals, and 3441, 4062 and 1935 cases of breast, colorectal and prostate cancer, respectively. None of the analyses showed a significant association of vegetarian diet and a lower risk of either breast, colorectal, and prostate cancer compared to a non-vegetarian diet. By contrast, a lower risk of colorectal cancer was associated with a semi-vegetarian diet (RR = 0.86, 95% confidence interval = 0.79-0.94; I 2 = 0%, P heterogeneity = 0.82) and a pesco-vegetarian diet (RR = 0.67, 95% confidence interval = 0.53, 0.83; I 2 = 0%, P heterogeneity = 0.46) compared to a non-vegetarian diet. The subgroup analysis by cancer localisation showed no differences in summary risk estimates between colon and rectal cancer. A summary of the existing evidence from cohort studies on vegetarian diets showed that complete exclusion of any source of protein from the diet is not associated with further benefits for human health. © 2016 The British Dietetic Association Ltd.

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.

PubMed

Mbeye, Nyanyiwe M; ter Kuile, Feiko O; Davies, Mary-Ann; Phiri, Kamija S; Egger, Matthias; Wandeler, Gilles

2014-09-01

Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children. © 2014 John Wiley & Sons Ltd.

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

PubMed

Shen, Ye; King, Charles H; Binder, Sue; Zhang, Feng; Whalen, Christopher C; Evan Secor, W; Montgomery, Susan P; Mwinzi, Pauline N M; Olsen, Annette; Magnussen, Pascal; Kinung'hi, Safari; Phillips, Anna E; Nalá, Rassul; Ferro, Josefo; Aurelio, H Osvaldo; Fleming, Fiona; Garba, Amadou; Hamidou, Amina; Fenwick, Alan; Campbell, Carl H; Colley, Daniel G

2017-09-29

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis. These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

Assessing the Genetic Predisposition of Education on Myopia: a Mendelian Randomization Study

PubMed Central

Cuellar-Partida, Gabriel; Lu, Yi; Kho, Pik Fang; Hewitt, Alex W.; Wichmann, H.-Erich; Yazar, Seyhan; Stambolian, Dwight; Bailey-Wilson, Joan E.; Wojciechowski, Robert; Wang, Jie Jin; Mitchell, Paul; Mackey, David A.; MacGregor, Stuart

2016-01-01

Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N=5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P=1.04×10−3). Our estimate of the effect of education on myopia was higher (P=0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [~2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error. PMID:26497973

Chemotherapy-induced neutropenia and the prognosis of colorectal cancer: a meta-analysis of cohort studies.

PubMed

Tan, XiangZhou; Wen, QiaoCheng; Wang, Ran; Chen, ZhiKang

2017-11-01

Recently, there has been a controversial discussion about the prognostic value of chemotherapy-induced neutropenia (CIN) in colorectal cancer patients. Thus, a meta-analysis was conducted to determine the relationship between CIN and the prognosis of colorectal cancer patients. We searched the PubMed, EMBASE, and Cochrane library databases to identify studies evaluating the association between CIN and colorectal cancer prognosis. Pooled random/fixed effect models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association. Eight studies were selected for the meta-analysis, for a total of 2,745 patients. There was significant improved survival among colorectal cancer patients with CIN (HR = 0.62, 95% CI = 0.47-0.76). However, significant heterogeneity was found (p = 0.000, Ι 2  = 75.0%). Through subgroup analysis, we could greatly eliminate the heterogeneity and found that neutropenia was associated with better survival in stage IV colorectal cancer patients, no matter the HR calculated by overall survival (OS) or progression-free survival (PFS). Meanwhile, the prognostic value of neutropenia in stage II/III colorectal cancer can be found when the HR is calculated by disease-free survival (DFS). Additionally, we observed significant differences after stratification according to various tumor stages, endpoints, and the use of G-CSF. Our results which, based on a cohort study, indicate that CIN is associated with improved survival in patients with colorectal cancer. However, further randomized controlled trials are warranted.

Surgical treatment of hepatocellular carcinoma: evidence-based outcomes.

PubMed

Yamazaki, Shintaro; Takayama, Tadatoshi

2008-02-07

Surgeons may be severely criticized from the perspective of evidence-based medicine because the majority of surgical publications appear not to be convincing. In the top nine surgical journals in 1996, half of the 175 publications refer to pilot studies lacking a control group, 18% to animal experiments, and only 5% to randomized controlled trials (RCT). There are five levels of clinical evidence: level 1 (randomized controlled trial), level 2 (prospective concurrent cohort study), level 3 (retrospective historical cohort study), level 4 (pre-post study), and level 5 (case report). Recently, a Japanese evidence-based guideline for the surgical treatment of hepatocellular carcinoma (HCC) was made by a committee (Chairman, Professor Makuuchi and five members). We searched the literature using the Medline Dialog System with four keywords: HCC, surgery, English papers, in the last 20 years. A total of 915 publications were identified systematically reviewed. At the first selection (in which surgery-dominant papers were selected), 478 papers survived. In the second selection (clearly concluded papers), 181 papers survived. In the final selection (clinically significant papers), 100 papers survived. The evidence level of the 100 surviving papers is shown here: level-1 papers (13%), level-2 papers (11%), level-3 papers (52%), and level-4 papers (24%); therefore, there were 24% prospective papers and 76% retrospective papers. Here, we present a part of the guideline on the five main surgical issues: indication to operation, operative procedure, peri-operative care, prognostic factor, and post-operative adjuvant therapy.

Surgical treatment of hepatocellular carcinoma: Evidence-based outcomes

PubMed Central

Yamazaki, Shintaro; Takayama, Tadatoshi

2008-01-01

Surgeons may be severely criticized from the perspective of evidence-based medicine because the majority of surgical publications appear not to be convincing. In the top nine surgical journals in 1996, half of the 175 publications refer to pilot studies lacking a control group, 18% to animal experiments, and only 5% to randomized controlled trials (RCT). There are five levels of clinical evidence: level 1 (randomized controlled trial), level 2 (prospective concurrent cohort study), level 3 (retrospective historical cohort study), level 4 (pre-post study), and level 5 (case report). Recently, a Japanese evidence-based guideline for the surgical treatment of hepatocellular carcinoma (HCC) was made by a committee (Chairman, Professor Makuuchi and five members). We searched the literature using the Medline Dialog System with four keywords: HCC, surgery, English papers, in the last 20 years. A total of 915 publications were identified systematically reviewed. At the first selection (in which surgery-dominant papers were selected), 478 papers survived. In the second selection (clearly concluded papers), 181 papers survived. In the final selection (clinically significant papers), 100 papers survived. The evidence level of the 100 surviving papers is shown here: level-1 papers (13%), level-2 papers (11%), level-3 papers (52%), and level-4 papers (24%); therefore, there were 24% prospective papers and 76% retrospective papers. Here, we present a part of the guideline on the five main surgical issues: indication to operation, operative procedure, peri-operative care, prognostic factor, and post-operative adjuvant therapy. PMID:18205256

Frequency distribution of gastro esophageal reflux disease in inhalation injury: A historical cohort study.

PubMed

Karbasi, Ashraf; Aliannejad, Rasoul; Ghanei, Mostafa; Sanamy, Mehran Noory; Alaeddini, Farshid; Harandi, Ali Amini

2015-07-01

There is no data on the prevalence and the association of gastro esophageal reflux disease (GERD) with toxic fume inhalation. Therefore, we aimed to evaluate the frequency distribution of GERD symptoms among the individuals with mild respiratory disorder due to the past history of toxic fume exposure to sulfur mustard (SM). In a historical cohort study, subjects were randomly selected from 7000 patients in a database of all those who had a history of previous exposure to a single high dose of SM gas during war. The control group was randomly selected from adjacent neighbors of the patients, and two healthy male subjects were chosen per patient. In this study, we used the validated Persian translation of Mayo Gastroesophageal Reflux Questionnaire to assess the frequency distribution of reflux disease. Relative frequency of GERD symptoms, was found to be significantly higher in the inhalation injury patients with an odds ratio of 8.30 (95% confidence interval [CI]: 4.73-14.55), and after adjustment for cigarette smoking, tea consumption, age, and body mass index, aspirin and chronic cough the odds ratio was found to be 4.41 (95% CI: 1.61-12.07). The most important finding of our study was the major GERD symptoms (heartburn and/or acid regurgitation once or more per week) among the individuals with the past history of exposure to SM toxic gas is substantially higher (4.4-fold) than normal populations.

Frequency distribution of gastro esophageal reflux disease in inhalation injury: A historical cohort study

PubMed Central

Karbasi, Ashraf; Aliannejad, Rasoul; Ghanei, Mostafa; Sanamy, Mehran Noory; Alaeddini, Farshid; Harandi, Ali Amini

2015-01-01

Background: There is no data on the prevalence and the association of gastro esophageal reflux disease (GERD) with toxic fume inhalation. Therefore, we aimed to evaluate the frequency distribution of GERD symptoms among the individuals with mild respiratory disorder due to the past history of toxic fume exposure to sulfur mustard (SM). Materials and Methods: In a historical cohort study, subjects were randomly selected from 7000 patients in a database of all those who had a history of previous exposure to a single high dose of SM gas during war. The control group was randomly selected from adjacent neighbors of the patients, and two healthy male subjects were chosen per patient. In this study, we used the validated Persian translation of Mayo Gastroesophageal Reflux Questionnaire to assess the frequency distribution of reflux disease. Results: Relative frequency of GERD symptoms, was found to be significantly higher in the inhalation injury patients with an odds ratio of 8.30 (95% confidence interval [CI]: 4.73-14.55), and after adjustment for cigarette smoking, tea consumption, age, and body mass index, aspirin and chronic cough the odds ratio was found to be 4.41 (95% CI: 1.61-12.07). Conclusion: The most important finding of our study was the major GERD symptoms (heartburn and/or acid regurgitation once or more per week) among the individuals with the past history of exposure to SM toxic gas is substantially higher (4.4-fold) than normal populations. PMID:26622251

Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study.

PubMed

Cuellar-Partida, Gabriel; Lu, Yi; Kho, Pik Fang; Hewitt, Alex W; Wichmann, H-Erich; Yazar, Seyhan; Stambolian, Dwight; Bailey-Wilson, Joan E; Wojciechowski, Robert; Wang, Jie Jin; Mitchell, Paul; Mackey, David A; MacGregor, Stuart

2016-01-01

Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P = 1.04 × 10(-3) ). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [∼2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error. © 2015 WILEY PERIODICALS, INC.

Descriptive epidemiology and prior healthcare utilization of patients in the Spine Patient Outcomes Research Trial's (SPORT) three observational cohorts: disc herniation, spinal stenosis, and degenerative spondylolisthesis.

PubMed

Cummins, Justin; Lurie, Jon D; Tosteson, Tor D; Hanscom, Brett; Abdu, William A; Birkmeyer, Nancy J O; Herkowitz, Harry; Weinstein, James

2006-04-01

Prospective observational cohorts. To describe sociodemographic and clinical features, and nonoperative (medical) resource utilization before enrollment, in patients who are candidates for surgical intervention for intervertebral disc herniation (IDH), spinal stenosis (SpS), and degenerative spondylolisthesis (DS) according to SPORT criteria. Intervertebral disc herniation, spinal stenosis, and degenerative spondylolisthesis with stenosis are the three most common diagnoses of low back and leg symptoms for which surgery is performed. There is a paucity of descriptive literature examining large patient cohorts for the relationships among baseline characteristics and medical resource utilization with these three diagnoses. The Spine Patient Outcomes Research Trial (SPORT) conducts three randomized and three observational cohort studies of surgical and nonsurgical treatments for patients with IDH, SpS, and DS. Baseline data include demographic information, prior treatments received, and functional status measured by SF-36 and the Oswestry Disability Index (ODI-AAOS/Modems version). The data presented represent all 1,411 patients (743 IDH, 365 SpS, 303 DS) enrolled in the SPORT observational cohorts. Multiple logistic regression was used to generate independent predictors of utilization adjusted for sociodemographic variables, diagnosis, and duration of symptoms. The average age was 41 years for the IDH group, 64 years for the SpS group, and 66 years for the DS group. At enrollment, IDH patients presented with the most pain as reported on the SF-36 (BP 26.3 vs. 33.2 SpS and 33.8 DS) and were the most impaired (ODI 51 vs. 42.3 SpS and 41.5 DS). IDH patients used more chiropractic treatment (42% vs. 33% SpS and 26% DS), had more Emergency Department (ED) visits (21% vs. 7% SpS and 4% DS), and used more opiate analgesics (49% vs. 29% SpS and 27% DS). After adjusting for age, gender, diagnosis, education, race, duration of symptoms, and compensation, Medicaid patients used significantly more opiate analgesics (58% Medicaid vs. 41% no insurance, 42% employer, 33% Medicare, and 32% private) and had more ED visits compared with other insurance types (31% Medicaid vs. 22% no insurance, 16% employer, 3% Medicare, and 11% private). IDH patients appear to have differences in sociodemographics, resource utilization, and functional impairment when compared with the SpS/DS patients. In addition, the differences in resource utilization for Medicaid patients may reflect differences in access to care. The data provided from these observational cohorts will serve as an important comparison to the SPORT randomized cohorts in the future.

Determining individual variation in growth and its implication for life-history and population processes using the empirical Bayes method.

PubMed

Vincenzi, Simone; Mangel, Marc; Crivelli, Alain J; Munch, Stephan; Skaug, Hans J

2014-09-01

The differences in demographic and life-history processes between organisms living in the same population have important consequences for ecological and evolutionary dynamics. Modern statistical and computational methods allow the investigation of individual and shared (among homogeneous groups) determinants of the observed variation in growth. We use an Empirical Bayes approach to estimate individual and shared variation in somatic growth using a von Bertalanffy growth model with random effects. To illustrate the power and generality of the method, we consider two populations of marble trout Salmo marmoratus living in Slovenian streams, where individually tagged fish have been sampled for more than 15 years. We use year-of-birth cohort, population density during the first year of life, and individual random effects as potential predictors of the von Bertalanffy growth function's parameters k (rate of growth) and L∞ (asymptotic size). Our results showed that size ranks were largely maintained throughout marble trout lifetime in both populations. According to the Akaike Information Criterion (AIC), the best models showed different growth patterns for year-of-birth cohorts as well as the existence of substantial individual variation in growth trajectories after accounting for the cohort effect. For both populations, models including density during the first year of life showed that growth tended to decrease with increasing population density early in life. Model validation showed that predictions of individual growth trajectories using the random-effects model were more accurate than predictions based on mean size-at-age of fish.

Dietary Inflammatory Potential Score and Risk of Breast Cancer: Systematic Review and Meta-analysis.

PubMed

Zahedi, Hoda; Djalalinia, Shirin; Sadeghi, Omid; Asayesh, Hamid; Noroozi, Mehdi; Gorabi, Armita Mahdavi; Mohammadi, Rasool; Qorbani, Mostafa

2018-02-07

Several studies have been conducted on the relationship between dietary inflammatory potential (DIP) and breast cancer. However, the findings are conflicting. This systematic review and meta-analysis summarizes the findings on the association between DIP and the risk of breast cancer. We used relevant keywords and searched online international electronic databases, including PubMed and NLM Gateway (for Medline), Institute for Scientific Information (ISI), and Scopus for articles published through February 2017. All cross-sectional, case-control, and cohort studies were included in this meta-analysis. Meta-analysis was performed using the random effects meta-analysis method to address heterogeneity among studies. Findings were analyzed statistically. Nine studies were included in the present systematic review and meta-analysis. The total sample size of these studies was 296,102, and the number of participants varied from 1453 to 122,788. The random effects meta-analysis showed a positive and significant association between DIP and the risk of breast cancer (pooled odds ratio, 1.14; 95% confidence interval, 1.01-1.27). The pooled effect size was not statistically significant because of the type of studies, including cohort (pooled relative risk, 1.04; 95% confidence interval, 0.98-1.10) and case-control (pooled odds ratio, 1.63; 95% confidence interval, 0.89-2.37) studies. We found a significant and positive association between higher DIP score and risk of breast cancer. Modifying inflammatory characteristics of diet can substantially reduce the risk of breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation.

PubMed

Favennec, Marie; Hennart, Benjamin; Caiazzo, Robert; Leloire, Audrey; Yengo, Loïc; Verbanck, Marie; Arredouani, Abdelilah; Marre, Michel; Pigeyre, Marie; Bessede, Alban; Guillemin, Gilles J; Chinetti, Giulia; Staels, Bart; Pattou, François; Balkau, Beverley; Allorge, Delphine; Froguel, Philippe; Poulain-Godefroy, Odile

2015-10-01

This study characterized the kynurenine pathway (KP) in human obesity by evaluating circulating levels of kynurenines and the expression of KP enzymes in adipose tissue. Tryptophan and KP metabolite levels were measured in serum of individuals from the D.E.S.I.R. cohort (case-cohort study: 212 diabetic, 836 randomly sampled) and in women with obesity, diabetic or normoglycemic, from the ABOS cohort (n = 100). KP enzyme gene expressions were analyzed in omental and subcutaneous adipose tissue of women from the ABOS cohort, in human primary adipocytes and in monocyte-derived macrophages. In the D.E.S.I.R. cohort, kynurenine levels were positively associated with body mass index (BMI) (P = 4.68 × 10(-19) ) and with a higher HOMA2-IR insulin resistance index (P = 6.23 × 10(-4) ). The levels of kynurenine, kynurenic acid, and quinolinic acid were associated with higher BMI (P < 0.05). The expression of several KP enzyme genes (indoleamine 2,3-dioxygenase 1 [IDO1], kynureninase [KYNU], kynurenine 3-monooxygenase [KMO], and kynurenine aminotransferase III [CCBL2]) was increased in the omental adipose tissue of women with obesity compared to lean (P < 0.05), and their expression was induced by proinflammatory cytokines in human primary adipocytes (P < 0.05), except for KMO that is not expressed in these cells. The expressions of IDO1, KYNU, KMO, and CCBL2 were higher in proinflammatory than in anti-inflammatory macrophages (P < 0.05). In the context of obesity, the presence of macrophages in adipose tissue may contribute to diverting KP toward KMO activation. © 2015 The Obesity Society.

Parent–offspring resemblance in colony-specific adult survival of cliff swallows

USGS Publications Warehouse

Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

2015-01-01

Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies

PubMed Central

Kelly, Jennifer L.; Salles, Gilles; Goldman, Bryan; Fisher, Richard I.; Brice, Pauline; Press, Oliver; Casasnovas, Olivier; Maloney, David G.; Soubeyran, Pierre; Rimsza, Lisa; Haioun, Corinne; Xerri, Luc; LeBlanc, Michael; Tilly, Hervé; Friedberg, Jonathan W.

2015-01-01

Purpose Recent literature reports a potential association between high vitamin D and improved lymphoma prognosis. We evaluated the impact of pretreatment vitamin D on follicular lymphoma (FL) outcome. Patients and Methods SWOG participants were previously untreated patients with FL enrolled onto SWOG clinical trials (S9800, S9911, or S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab) between 1998 and 2008. Participants included in our second independent cohort were also previously untreated patients with FL enrolled onto the Lymphoma Study Association (LYSA) PRIMA trial of rituximab plus chemotherapy (randomly assigned to rituximab maintenance v observation) between 2004 and 2007. Using the gold-standard liquid chromatography–tandem mass spectrometry method, 25-hydroxyvitamin D was measured in stored baseline serum samples. The primary end point was progression-free survival (PFS). Results After a median follow-up of 5.4 years, the adjusted PFS and overall survival hazard ratios for the SWOG cohort were 1.97 (95% CI, 1.10 to 3.53) and 4.16 (95% CI, 1.66 to 10.44), respectively, for those who were vitamin D deficient (< 20 ng/mL; 15% of cohort). After a median follow-up of 6.6 years, the adjusted PFS and overall survival hazard ratios for the LYSA cohort were 1.50 (95% CI, 0.93 to 2.42) and 1.92 (95% CI, 0.72 to 5.13), respectively, for those who were vitamin D deficient (< 10 ng/mL; 25% of cohort). Conclusion Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival. Further investigation is needed to determine the effects of vitamin D supplementation in this clinical setting. PMID:25823738

Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies.

PubMed

Kelly, Jennifer L; Salles, Gilles; Goldman, Bryan; Fisher, Richard I; Brice, Pauline; Press, Oliver; Casasnovas, Olivier; Maloney, David G; Soubeyran, Pierre; Rimsza, Lisa; Haioun, Corinne; Xerri, Luc; LeBlanc, Michael; Tilly, Hervé; Friedberg, Jonathan W

2015-05-01

Recent literature reports a potential association between high vitamin D and improved lymphoma prognosis. We evaluated the impact of pretreatment vitamin D on follicular lymphoma (FL) outcome. SWOG participants were previously untreated patients with FL enrolled onto SWOG clinical trials (S9800, S9911, or S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab) between 1998 and 2008. Participants included in our second independent cohort were also previously untreated patients with FL enrolled onto the Lymphoma Study Association (LYSA) PRIMA trial of rituximab plus chemotherapy (randomly assigned to rituximab maintenance v observation) between 2004 and 2007. Using the gold-standard liquid chromatography-tandem mass spectrometry method, 25-hydroxyvitamin D was measured in stored baseline serum samples. The primary end point was progression-free survival (PFS). After a median follow-up of 5.4 years, the adjusted PFS and overall survival hazard ratios for the SWOG cohort were 1.97 (95% CI, 1.10 to 3.53) and 4.16 (95% CI, 1.66 to 10.44), respectively, for those who were vitamin D deficient (< 20 ng/mL; 15% of cohort). After a median follow-up of 6.6 years, the adjusted PFS and overall survival hazard ratios for the LYSA cohort were 1.50 (95% CI, 0.93 to 2.42) and 1.92 (95% CI, 0.72 to 5.13), respectively, for those who were vitamin D deficient (< 10 ng/mL; 25% of cohort). Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival. Further investigation is needed to determine the effects of vitamin D supplementation in this clinical setting. © 2015 by American Society of Clinical Oncology.

Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.

PubMed

Viney, Nicholas J; van Capelleveen, Julian C; Geary, Richard S; Xia, Shuting; Tami, Joseph A; Yu, Rosie Z; Marcovina, Santica M; Hughes, Steven G; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T; Witztum, Joseph L; Stroes, Erik S; Tsimikas, Sotirios

2016-11-05

Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations. We did two randomised, double-blind, placebo-controlled trials. In a phase 2 trial (done in 13 study centres in Canada, the Netherlands, Germany, Denmark, and the UK), we assessed the effect of IONIS-APO(a) Rx , an oligonucleotide targeting apolipoprotein(a). Participants with elevated Lp(a) concentrations (125-437 nmol/L in cohort A; ≥438 nmol/L in cohort B) were randomly assigned (in a 1:1 ratio in cohort A and in a 4:1 ratio in cohort B) with an interactive response system to escalating-dose subcutaneous IONIS-APO(a) Rx (100 mg, 200 mg, and then 300 mg, once a week for 4 weeks each) or injections of saline placebo, once a week, for 12 weeks. Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration at day 85 or 99 in the per-protocol population (participants who received more than six doses of study drug) and safety and tolerability in the safety population. In a phase 1/2a first-in-man trial, we assessed the effect of IONIS-APO(a)-L Rx , a ligand-conjugated antisense oligonucleotide designed to be highly and selectively taken up by hepatocytes, at the BioPharma Services phase 1 unit (Toronto, ON, Canada). Healthy volunteers (Lp[a] ≥75 nmol/L) were randomly assigned to receive a single dose of 10-120 mg IONIS-APO(a)L Rx subcutaneously in an ascending-dose design or placebo (in a 3:1 ratio; single-ascending-dose phase), or multiple doses of 10 mg, 20 mg, or 40 mg IONIS-APO(a)L Rx subcutaneously in an ascending-dose design or placebo (in an 8:2 ratio) at day 1, 3, 5, 8, 15, and 22 (multiple-ascending-dose phase). Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration, safety, and tolerability at day 30 in the single-ascending-dose phase and day 36 in the multiple-ascending-dose phase in participants who were randomised and received at least one dose of study drug. In both trials, the randomised allocation sequence was generated by Ionis Biometrics or external vendor with a permuted-block randomisation method. Participants, investigators, sponsor personnel, and clinical research organisation staff who analysed the data were all masked to the treatment assignments. Both trials are registered with ClinicalTrials.gov, numbers NCT02160899 and NCT02414594. From June 25, 2014, to Nov 18, 2015, we enrolled 64 participants to the phase 2 trial (51 in cohort A and 13 in cohort B). 35 were randomly assigned to IONIS-APO(a) Rx and 29 to placebo. At day 85/99, participants assigned to IONIS-APO(a) Rx had mean Lp(a) reductions of 66·8% (SD 20·6) in cohort A and 71·6% (13·0) in cohort B (both p<0·0001 vs pooled placebo). From April 15, 2015, to Jan 11, 2016, we enrolled 58 healthy volunteers to the phase 1/2a trial of IONIS-APO(a)-L Rx . Of 28 participants in the single-ascending-dose phase, three were randomly assigned to 10 mg, three to 20 mg, three to 40 mg, six to 80 mg, six to 120 mg, and seven to placebo. Of 30 participants in the multiple-ascending-dose phase, eight were randomly assigned to 10 mg, eight to 20 mg, eight to 40 mg, and six to placebo. Significant dose-dependent reductions in mean Lp(a) concentrations were noted in all single-dose IONIS-APO(a)-L Rx groups at day 30. In the multidose groups, IONIS-APO(a)-L Rx resulted in mean reductions in Lp(a) of 66% (SD 21·8) in the 10 mg group, 80% (SD 13·7%) in the 20 mg group, and 92% (6·5) in the 40 mg group (p=0·0007 for all vs placebo) at day 36. Both antisense oligonucleotides were safe. There were two serious adverse events (myocardial infarctions) in the IONIS-APO(a) Rx phase 2 trial, one in the IONIS-APO(a) Rx and one in the placebo group, but neither were thought to be treatment related. 12% of injections with IONIS-APO(a) Rx were associated with injection-site reactions. IONIS-APO(a)-L Rx was associated with no injection-site reactions. IONIS-APO(a)-L Rx is a novel, tolerable, potent therapy to reduce Lp(a) concentrations. IONIS-APO(a)-L Rx might mitigate Lp(a)-mediated cardiovascular risk and is being developed for patients with elevated Lp(a) concentrations with existing cardiovascular disease or calcific aortic valve stenosis. Ionis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Attention deficit/hyperactivity disorder and risk of injuries: A systematic review and meta-analysis

PubMed Central

Amiri, Shahrokh; Sadeghi-Bazargani, Homayoun; Nazari, Soulmaz; Ranjbar, Fatemeh; Abdi, Salman

2017-01-01

Abstract: Background: This study systematically reviewed the literature in order to determine the effect of Attention-Deficit Hyperactivity Disorder (ADHD) on injuries and assessed the magnitude of the potential association. Methods: A systematic review of the studies examining the association of ADHD and injuries was carried out across multiple databases. Odds ratios and standardized mean differences were pooled. Results: A total of 35 studies were selected for quantitative analysis. The association of ADHD and injuries was confirmed over the meta-analysis of eligible studies. The odds ratio pooled over all comparative studies was 1.96(95% CI: 1.6-2.4) using random effects model. Pooled odds ratio of 2.1 and 2.17 were calculated respectively when cohort and case-control studies or just cohort studies were included. The pooled odds ratio reduced to 1.8(CI:1.45-2.3) when studies on specific injuries were removed. For studies comparing scores of rating scales, the pooled standardized mean difference was 0.61(95% CI: 0.03-1.2). Conclusions: Those with ADHD are nearly two times more likely to be injured. PMID:28554188

The association between glomus tumors and neurofibromatosis.

PubMed

Harrison, Bridget; Moore, Amy M; Calfee, Ryan; Sammer, Douglas M

2013-08-01

To determine whether an epidemiologic association exists between glomus tumors and neurofibromatosis. Using a pathology database, we established a study cohort consisting of all patients who had undergone excision of a glomus tumor of the hand between 1995 and 2010. We created a control cohort by randomly selecting 200 patients who had undergone excision of a ganglion cyst over the same period. We reviewed medical records for each cohort to identify patients with a diagnosis of neurofibromatosis. We calculated the odds ratio was calculated and performed Fisher's exact test to determine the significance of the association. We identified 21 patients with glomus tumors of the hand. Six of these patients carried the diagnosis of neurofibromatosis (29%). In contrast, no patients in the control group carried the diagnosis of neurofibromatosis. The odds ratio for a diagnosis of neurofibromatosis in association with a glomus tumor compared with controls was 168:1. This study provides evidence of a strong epidemiologic association between glomus tumors and neurofibromatosis. Glomus tumor should be included in the differential diagnosis in neurofibromatosis patients who present with a painful lesion of the hand or finger. Diagnostic III. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Are effort-reward imbalance and social isolation mediating the association between education and depressiveness? Baseline findings from the lidA(§)-study.

PubMed

du Prel, Jean-Baptist; Iskenius, Mario; Peter, Richard

2014-12-01

To investigate multiple mediations of the association between education and depressive symptoms (BDI-V) by work-related stress (ERI) and social isolation, the regional variation of the first mediation and a potential moderating effect of regional unemployment rate. 6339 employees born in 1959 and 1965 were randomly recruited from 222 sample points in a German cohort study on work, age, health and work participation. A multilevel model of moderated lower-level mediation was used to investigate the confirmatory research question. Multiple mediations were tested corresponding to Baron and Kenny. These analyses were stratified for age and adjusted for sex, negative affectivity and overcommitment. In the association between education and depressive symptoms, indirect effects of work-related stress and social isolation were significant in both age cohorts whereas a direct association was observable in the younger cohort, only. The significant regional variation in the association between work-related stress and depressive symptoms was not statistically explained by regional unemployment rate. Our findings point out that work-related stress and social isolation play an intermediary role between education and depressive symptoms in middle-aged employees.

Seeking out SARI: an automated search of electronic health records.

PubMed

O'Horo, John C; Dziadzko, Mikhail; Sakusic, Amra; Ali, Rashid; Sohail, M Rizwan; Kor, Daryl J; Gajic, Ognjen

2018-06-01

The definition of severe acute respiratory infection (SARI) - a respiratory illness with fever and cough, occurring within the past 10 days and requiring hospital admission - has not been evaluated for critically ill patients. Using integrated electronic health records data, we developed an automated search algorithm to identify SARI cases in a large cohort of critical care patients and evaluate patient outcomes. We conducted a retrospective cohort study of all admissions to a medical intensive care unit from August 2009 through March 2016. Subsets were randomly selected for deriving and validating a search algorithm, which was compared with temporal trends in laboratory-confirmed influenza to ensure that SARI was correlated with influenza. The algorithm was applied to the cohort to identify clinical differences for patients with and without SARI. For identifying SARI, the algorithm (sensitivity, 86.9%; specificity, 95.6%) outperformed billing-based searching (sensitivity, 73.8%; specificity, 78.8%). Automated searching correlated with peaks in laboratory-confirmed influenza. Adjusted for severity of illness, SARI was associated with more hospital, intensive care unit and ventilator days but not with death or dismissal to home. The search algorithm accurately identified SARI for epidemiologic study and surveillance.

Maternal and perinatal mortality by place of delivery in sub-Saharan Africa: a meta-analysis of population-based cohort studies.

PubMed

Chinkhumba, Jobiba; De Allegri, Manuela; Muula, Adamson S; Robberstad, Bjarne

2014-09-28

Facility-based delivery has gained traction as a key strategy for reducing maternal and perinatal mortality in developing countries. However, robust evidence of impact of place of delivery on maternal and perinatal mortality is lacking. We aimed to estimate the risk of maternal and perinatal mortality by place of delivery in sub-Saharan Africa. We conducted a systematic review of population-based cohort studies reporting on risk of maternal or perinatal mortality at the individual level by place of delivery in sub-Saharan Africa. Newcastle-Ottawa Scale was used to assess study quality. Outcomes were summarized in pooled analyses using fixed and random effects models. We calculated attributable risk percentage reduction in mortality to estimate exposure effect. We report mortality ratios, crude odds ratios and associated 95% confidence intervals. We found 9 population-based cohort studies: 6 reporting on perinatal and 3 on maternal mortality. The mean study quality score was 10 out of 15 points. Control for confounders varied between the studies. A total of 36,772 pregnancy episodes were included in the analyses. Overall, perinatal mortality is 21% higher for home compared to facility-based deliveries, but the difference is only significant when produced with a fixed effects model (OR 1.21, 95% CI: 1.02-1.46) and not when produced by a random effects model (OR 1.21, 95% CI: 0.79-1.84). Under best settings, up to 14 perinatal deaths might be averted per 1000 births if the women delivered at facilities instead of homes. We found significantly increased risk of maternal mortality for facility-based compared to home deliveries (OR 2.29, 95% CI: 1.58-3.31), precluding estimates of attributable risk fraction. Evaluating the impact of facility-based delivery strategy on maternal and perinatal mortality using population-based studies is complicated by selection bias and poor control of confounders. Studies that pool data at an individual level may overcome some of these problems and provide better estimates of relative effectiveness of place of delivery in the region.

A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprim-sulfamethoxazole a real option?

PubMed

Hernandez, A V; Thota, P; Pellegrino, D; Pasupuleti, V; Benites-Zapata, V A; Deshpande, A; Penalva de Oliveira, A C; Vidal, J E

2017-02-01

The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent. We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82-1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02-1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24-0.97). The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed. © 2016 British HIV Association.

Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis.

PubMed

Anderson, Jana J; Darwis, Narisa D M; Mackay, Daniel F; Celis-Morales, Carlos A; Lyall, Donald M; Sattar, Naveed; Gill, Jason M R; Pell, Jill P

2018-02-01

Red and processed meat may be risk factors for breast cancer due to their iron content, administration of oestrogens to cattle or mutagens created during cooking. We studied the associations in UK Biobank and then included the results in a meta-analysis of published cohort studies. UK Biobank, a general population cohort study, recruited participants aged 40-69 years. Incident breast cancer was ascertained via linkage to routine hospital admission, cancer registry and death certificate data. Univariate and multivariable Cox proportional hazard models were used to explore the associations between red and processed meat consumption and breast cancer. Previously published cohort studies were identified from a systematic review using PubMed and Ovid and a meta-analysis conducted using a random effects model. Over a median of 7 years follow-up, 4819 of the 262,195 women developed breast cancer. The risk was increased in the highest tertile (>9 g/day) of processed meat consumption (adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.08-1.35, p = 0.001). Collation with 10 previous cohort studies provided data on 40,257 incident breast cancers in 1.65 million women. On meta-analysis, processed meat consumption was associated with overall (relative risk [RR] 1.06, 95% CI 1.01-1.11) and post-menopausal (RR 1.09, 95% CI 1.03-1.15), but not pre-menopausal (RR 0.99, 95% CI 0.88-1.10), breast cancer. In UK Biobank and the meta-analysis, red meat consumption was not associated with breast cancer (adjusted HR 0.99 95% CI 0.88-1.12 and RR 1.03, 95% CI 0.99-1.08, respectively). Consumption of processed meat, but not red meat, may increase the risk of breast cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort

PubMed Central

Budhathoki, Sanjeev; Hidaka, Akihisa; Sawada, Norie; Tanaka-Mizuno, Sachiko; Kuchiba, Aya; Charvat, Hadrien; Goto, Atsushi; Kojima, Satoshi; Sudo, Natsuki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro; Iwasaki, Motoki

2018-01-01

Abstract Objective To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. Design Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. Setting Nine public health centre areas across Japan. Participants 3301 incident cases of cancer and 4044 randomly selected subcohort participants. Exposure Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. Main outcome measure Incidence of overall or site specific cancer. Results Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. Conclusions In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites. PMID:29514781

Classification and appraisal of the level of clinical evidence of publications from the Canadian Association of Pediatric Surgeons for the past 10 years.

PubMed

Al-Harbi, Khalad; Farrokhyar, Forough; Mulla, Sohail; Fitzgerald, Peter

2009-05-01

Increasing evidence is placed on the evidence-based quality of publications. We classified the publication type and assessed the reporting quality of the highest evidence level publications from the Canadian Association of Pediatric Surgeons between 1998 and 2007. All publications from Canadian Association of Pediatric Surgeons issues in the Journal of Pediatric Surgery from 1998 to 2007 were classified by study type and level of evidence (Oxford Center for Evidence-based Medicine Levels of Evidence). Cohort studies (level 2) were evaluated by 2 independent assessors using the Newcastle-Ottawa Quality Assessment Scale (NOQAS). Reliability and chi(2) analyses were performed. Three hundred two publications were classified by level of evidence as follows: level 2, 46; level 3, 13; level 4, 109; and level 5, 134. The median NOQAS score of the 46 level-2 cohort studies was 8 (range, 5-9), and the interrater reliability was 0.94 (95% confidence interval, 0.89-0.96). There was a significant increase in the number of level-2 evidence publications (P = .001) over the study period. Level-2 evidence cohort studies met a high scientific standard as assessed by the NOQAS and significantly increased in number over the study period. However, there were no level-1 evidence (randomized controlled trial) publications, and most were in the lower evidence classification levels (3-5).

Cohort profile: the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) in Korea.

PubMed

Seong, Sang Cheol; Kim, Yeon-Yong; Park, Sue K; Khang, Young Ho; Kim, Hyeon Chang; Park, Jong Heon; Kang, Hee-Jin; Do, Cheol-Ho; Song, Jong-Sun; Lee, Eun-Joo; Ha, Seongjun; Shin, Soon Ae; Jeong, Seung-Lyeal

2017-09-24

The National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) is a cohort of participants who participated in health screening programmes provided by the NHIS in the Republic of Korea. The NHIS constructed the NHIS-HEALS cohort database in 2015. The purpose of this cohort is to offer relevant and useful data for health researchers, especially in the field of non-communicable diseases and health risk factors, and policy-maker. To construct the NHIS-HEALS database, a sample cohort was first selected from the 2002 and 2003 health screening participants, who were aged between 40 and 79 in 2002 and followed up through 2013. This cohort included 514 866 health screening participants who comprised a random selection of 10% of all health screening participants in 2002 and 2003. The age-standardised prevalence of anaemia, diabetes mellitus, hypertension, obesity, hypercholesterolaemia and abnormal urine protein were 9.8%, 8.2%, 35.6%, 2.7%, 14.2% and 2.0%, respectively. The age-standardised mortality rate for the first 2 years (through 2004) was 442.0 per 100 000 person-years, while the rate for 10 years (through 2012) was 865.9 per 100 000 person-years. The most common cause of death was malignant neoplasm in both sexes (364.1 per 100 000 person-years for men, 128.3 per 100 000 person-years for women). This database can be used to study the risk factors of non-communicable diseases and dental health problems, which are important health issues that have not yet been fully investigated. The cohort will be maintained and continuously updated by the NHIS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Association of an inter-arm systolic blood pressure difference with all-cause and cardiovascular mortality: An updated meta-analysis of cohort studies.

PubMed

Cao, Kaiwu; Xu, Jingsong; Shangguan, Qing; Hu, Weitong; Li, Ping; Cheng, Xiaoshu; Su, Hai

2015-01-01

To evaluate whether an association exists between an inter-arm systolic blood pressure difference (sIAD) and all-cause and cardiovascular mortality. We searched for cohort studies that evaluated the association of a sIAD and all-cause or cardiovascular mortality in the electronic databases Medline/PubMed and Embase (August 2014). Random effects models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Nine cohort studies (4 prospective and 5 retrospective) enrolling 15,617 participants were included. The pooled HR of all-cause mortality for a sIAD of ≥ 10 mm Hg was 1.53 (95% CI 1.14-2.06), and that for a sIAD of ≥ 15 mm Hg was 1.46 (1.13-1.88). Pooled HRs of cardiovascular mortality were 2.21 (95% CI 1.52-3.21) for a sIAD of ≥ 10mm Hg, and 1.89 (1.32-2.69) for a sIAD of ≥ 15 mm Hg. In the patient-based cohorts including hospital- and diabetes-based cohorts, both sIADs of ≥ 10 and ≥ 15 mm Hg were associated with increased all-cause (pooled HR 1.95, 95% CI 1.01-3.78 and 1.59, 1.06-2.38, respectively) and cardiovascular mortality (pooled HR 2.98, 95% CI 1.88-4.72 and 2.10, 1.07-4.13, respectively). In the community-based cohorts, however, only a sIAD of ≥ 15 mm Hg was associated with increased cardiovascular mortality (pooled HR 1.94, 95 % CI 1.12-3.35). In the patient populations, a sIAD of ≥ 10 or of ≥ 15 mm Hg could be a useful indictor for increased all-cause and cardiovascular mortality, and a sIAD of ≥ 15 mm Hg might help to predict increased cardiovascular mortality in the community populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Coffee intake and the incident risk of cognitive disorders: A dose-response meta-analysis of nine prospective cohort studies.

PubMed

Wu, Lei; Sun, Dali; He, Yao

2017-06-01

Previous epidemiological studies have provided inconsistent conclusions on the impact of coffee consumption in the developing of cognitive disorders. However, no previous meta-analysis has pooled the evidence from the prospective cohort studies to assess the influence of coffee drinking and its potential dose-response patterns on the risk of developing cognitive disorders specifically. Two databases (PubMed and Embase) were searched for evidence of cohort studies from inception to February 2016. We used a generic inverse-variance method with a random-effects model to pool the fully adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). In the dose-response analyses, a generalized least-squares trend estimation model was applied to computing the study-specific slopes. Nine prospective cohort studies involving 34,282 participants were included in our study. The duration of follow-up years ranged from 1.3 to 28. Compared with <1 cup, daily drinking of 1-2 cups of coffee was inversely linked with the occurrence of cognitive disorders (i.e., Alzheimer's disease, dementia, cognitive decline, and cognitive impairment), and the pooled RR (95% CI) was 0.82 (0.71, 0.94) with evidence of non-significant heterogeneity (I 2  = 25%). Non-significant differences were presented for the association between coffee consumption (>3 vs. <1 cup/d) and incident cognitive disorders. The dose-response analysis showed a "J-shaped" curve relationship of the risk of developing cognitive disorders with coffee consumption. A "J-shaped" association was presented between coffee intake and incident cognitive disorders, with the lowest risk of incident cognitive disorders at a daily consumption level of 1-2 cups of coffee. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Attention Deficit/Hyperactivity Disorder and Childhood Autism in Association with Prenatal Exposure to Perfluoroalkyl Substances: A Nested Case–Control Study in the Danish National Birth Cohort

PubMed Central

Liew, Zeyan; Ritz, Beate; von Ehrenstein, Ondine S.; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Fei, Chunyuan; Bossi, Rossana; Henriksen, Tine Brink; Bonefeld-Jørgensen, Eva Cecilie

2014-01-01

Background: Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited. Objectives: We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children. Methods: Among 83,389 mother–child pairs enrolled in the Danish National Birth Cohort during 1996–2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child’s sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights. Results: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother’s PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise. Conclusions: In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children. Citation: Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei CY, Bossi R, Henriksen TB, Bonefeld-Jørgensen EC, Olsen J. 2015. Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case–control study in the Danish National Birth Cohort. Environ Health Perspect 123:367–373; http://dx.doi.org/10.1289/ehp.1408412 PMID:25616253

Jim Crow and Premature Mortality Among the US Black and White Population, 1960–2009

PubMed Central

Krieger, Nancy; Chen, Jarvis T.; Coull, Brent A.; Beckfield, Jason; Kiang, Mathew V.; Waterman, Pamela D.

2016-01-01

Background Scant research has analyzed the health impact of abolition of Jim Crow (ie, legal racial discrimination overturned by the US 1964 Civil Rights Act). Methods We used hierarchical age–period–cohort models to analyze US national black and white premature mortality rates (death before 65 years of age) in 1960–2009. Results Within a context of declining US black and white premature mortality rates and a persistent 2-fold excess black risk of premature mortality in both the Jim Crow and non-Jim Crow states, analyses including random period, cohort, state, and county effects and fixed county income effects found that, within the black population, the largest Jim Crow-by-period interaction occurred in 1960–1964 (mortality rate ratio [MRR] = 1.15 [95% confidence interval = 1.09–1.22), yielding the largest overall period-specific Jim Crow effect MRR of 1.27, with no such interactions subsequently observed. Furthermore, the most elevated Jim Crow-by-cohort effects occurred for birth cohorts from 1901 through 1945 (MRR range = 1.05–1.11), translating to the largest overall cohort-specific Jim Crow effect MRRs for the 1921–1945 birth cohorts (MRR ~ 1.2), with no such interactions subsequently observed. No such interactions between Jim Crow and either period or cohort occurred among the white population. Conclusion Together, the study results offer compelling evidence of the enduring impact of both Jim Crow and its abolition on premature mortality among the US black population, although insufficient to eliminate the persistent 2-fold black excess risk evident in both the Jim Crow and non-Jim Crow states from 1960 to 2009. PMID:24825344

Predicting Early Mortality After Hip Fracture Surgery: The Hip Fracture Estimator of Mortality Amsterdam.

PubMed

Karres, Julian; Kieviet, Noera; Eerenberg, Jan-Peter; Vrouenraets, Bart C

2018-01-01

Early mortality after hip fracture surgery is high and preoperative risk assessment for the individual patient is challenging. A risk model could identify patients in need of more intensive perioperative care, provide insight in the prognosis, and allow for risk adjustment in audits. This study aimed to develop and validate a risk prediction model for 30-day mortality after hip fracture surgery: the Hip fracture Estimator of Mortality Amsterdam (HEMA). Data on 1050 consecutive patients undergoing hip fracture surgery between 2004 and 2010 were retrospectively collected and randomly split into a development cohort (746 patients) and validation cohort (304 patients). Logistic regression analysis was performed in the development cohort to determine risk factors for the HEMA. Discrimination and calibration were assessed in both cohorts using the area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow goodness-of-fit test, and by stratification into low-, medium- and high-risk groups. Nine predictors for 30-day mortality were identified and used in the final model: age ≥85 years, in-hospital fracture, signs of malnutrition, myocardial infarction, congestive heart failure, current pneumonia, renal failure, malignancy, and serum urea >9 mmol/L. The HEMA showed good discrimination in the development cohort (AUC = 0.81) and the validation cohort (AUC = 0.79). The Hosmer-Lemeshow test indicated no lack of fit in either cohort (P > 0.05). The HEMA is based on preoperative variables and can be used to predict the risk of 30-day mortality after hip fracture surgery for the individual patient. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

The competing risks Cox model with auxiliary case covariates under weaker missing-at-random cause of failure.

PubMed

Nevo, Daniel; Nishihara, Reiko; Ogino, Shuji; Wang, Molin

2017-08-04

In the analysis of time-to-event data with multiple causes using a competing risks Cox model, often the cause of failure is unknown for some of the cases. The probability of a missing cause is typically assumed to be independent of the cause given the time of the event and covariates measured before the event occurred. In practice, however, the underlying missing-at-random assumption does not necessarily hold. Motivated by colorectal cancer molecular pathological epidemiology analysis, we develop a method to conduct valid analysis when additional auxiliary variables are available for cases only. We consider a weaker missing-at-random assumption, with missing pattern depending on the observed quantities, which include the auxiliary covariates. We use an informative likelihood approach that will yield consistent estimates even when the underlying model for missing cause of failure is misspecified. The superiority of our method over naive methods in finite samples is demonstrated by simulation study results. We illustrate the use of our method in an analysis of colorectal cancer data from the Nurses' Health Study cohort, where, apparently, the traditional missing-at-random assumption fails to hold.

Knee osteoarthritis and role for surgical intervention: lessons learned from randomized clinical trials and population-based cohorts.

PubMed

Buchbinder, Rachelle; Richards, Bethan; Harris, Ian

2014-03-01

Over the last decade, there has been increased recognition of the importance of high-quality randomized controlled trials in determining the role of surgery for knee osteoarthritis. This review highlights key findings from the best available studies, and considers whether or not this knowledge has resulted in better evidence-based care. Use of arthroscopy to treat knee osteoarthritis has not declined despite strong evidence-based recommendations that do not sanction its use. A large randomized controlled trial has demonstrated that arthroscopic partial meniscectomy followed by a standardized physical therapy program results in similar improvements in pain and function at 6 and 12 months in comparison to physical therapy alone in patients with knee osteoarthritis and a symptomatic meniscal tear, confirming the findings of two previous trials. Two recent randomized controlled trials have demonstrated that decision aids help people to reach better-informed decisions about total knee arthroplasty. A majority of studies have indicated that for people with obesity the positive results of total knee arthroplasty may be compromised by postoperative complications, particularly infection. More efforts are needed to overcome significant evidence-practice gaps in the surgical management of knee osteoarthritis, particularly arthroscopy. Decision aids are a promising tool.

Mutation Frequency of the Major Frontotemporal Dementia Genes, MAPT, GRN and C9ORF72 in a Turkish Cohort of Dementia Patients.

PubMed

Guven, Gamze; Lohmann, Ebba; Bras, Jose; Gibbs, J Raphael; Gurvit, Hakan; Bilgic, Basar; Hanagasi, Hasmet; Rizzu, Patrizia; Heutink, Peter; Emre, Murat; Erginel-Unaltuna, Nihan; Just, Walter; Hardy, John; Singleton, Andrew; Guerreiro, Rita

2016-01-01

'Microtubule-associated protein tau' (MAPT), 'granulin' (GRN) and 'chromosome 9 open reading frame72' (C9ORF72) gene mutations are the major known genetic causes of frontotemporal dementia (FTD). Recent studies suggest that mutations in these genes may also be associated with other forms of dementia. Therefore we investigated whether MAPT, GRN and C9ORF72 gene mutations are major contributors to dementia in a random, unselected Turkish cohort of dementia patients. A combination of whole-exome sequencing, Sanger sequencing and fragment analysis/Southern blot was performed in order to identify pathogenic mutations and novel variants in these genes as well as other FTD-related genes such as the 'charged multivesicular body protein 2B' (CHMP2B), the 'FUS RNA binding protein' (FUS), the 'TAR DNA binding protein' (TARDBP), the 'sequestosome1' (SQSTM1), and the 'valosin containing protein' (VCP). We determined one pathogenic MAPT mutation (c.1906C>T, p.P636L) and one novel missense variant (c.38A>G, p.D13G). In GRN we identified a probably pathogenic TGAG deletion in the splice donor site of exon 6. Three patients were found to carry the GGGGCC expansions in the non-coding region of the C9ORF72 gene. In summary, a complete screening for mutations in MAPT, GRN and C9ORF72 genes revealed a frequency of 5.4% of pathogenic mutations in a random cohort of 93 Turkish index patients with dementia.

Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia.

PubMed

Akdim, Fatima; Tribble, Diane L; Flaim, JoAnn D; Yu, Rosie; Su, John; Geary, Richard S; Baker, Brenda F; Fuhr, Rainard; Wedel, Mark K; Kastelein, John J P

2011-11-01

Mipomersen, an apolipoprotein (apo) B synthesis inhibitor, has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers. A randomized, double-blind, placebo-controlled, dose-escalation study was designed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia. Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 randomization ratio of active to placebo. Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week. Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins. In the 200 and 300 mg/week dose cohorts, mean reductions from baseline in LDL cholesterol were -45 ± 10% (P= 0.000) and -61 ± 8% (P= 0.000), corresponding to a -46 ± 11% (P= 0.000) and -61 ± 7% (P= 0.000) decrease in apoB levels. Triglyceride levels were also lowered with median reductions up to 53% (P= 0.021). The most common adverse events were injection site reactions. Seven of 40 subjects (18%) showed consecutive transaminase elevations >3× upper limit of normal. Five of these subjects received 400 mg/week, four of whom had apoB levels below the limit of detection. As a consequence, the 400 mg/week cohort was discontinued. Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins. Higher doses were associated with hepatic transaminase increases.

Are Locking Constructs in Distal Femoral Fractures Always Best? A Prospective Multicenter Randomized Controlled Trial Comparing the Less Invasive Stabilization System With the Minimally Invasive Dynamic Condylar Screw System.

PubMed

2016-01-01

The purpose of this clinical study is to determine whether the rate of fracture healing and fracture union, repaired with a locked device, will be as good as or better than standard nonlocking bicortical fixation in distal femoral fractures. Institutional review board-approved, multicenter prospective randomized controlled trial. Seven level 1 trauma centers across Canada. Fifty-two patients with distal femoral fractures (AO/OTA 33A1 to 33C2) were enrolled in the randomized trial. Twelve AO/OTA 33C3 fractures were excluded from the randomized trial but followed up as a nonrandomized cohort. Patients were treated through a standardized minimally invasive approach. Fractures were randomized 1:1 to treatment with the locked Less Invasive Stabilization System (LISS; Synthes, Paoli, PA) or the dynamic condylar screw (DCS). The nonrandomized cohort was treated at the surgeon's discretion. Primary outcomes were time to radiological union and number of delayed/nonunions at 12 months. Secondary outcomes were postoperative function and complications. Fifty-two patients were randomized including 34 women and 18 men. The mean age was 59 years. Twenty-eight patients were treated with the LISS and 24 with the DCS. There was no statistically significant difference between the LISS and the DCS in terms of the number of fractures healed, time to union, or functional scores. Complications and revisions were more common in the LISS group. There were 7 reoperations in the LISS group and one in the DCS group. Only 52% of the LISS group healed without intervention by 12 months compared with 91% in the DCS group. There was no advantage to the locking plate design in the management of distal femoral fractures in this study. The higher cost of the locking plates, challenges in technique, and lack of superiority have led the authors to discontinue the use of this lateral unicortical locking device in favor of other devices that allow locked or nonlocked bicortical fixation, articular compression, and bridging of the comminuted fracture segments. The cost-effective treatment for a subgroup or periarticular fractures may be a fixed-angle nonlocked device in patients with reasonable bone quality. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

Overall mortality among patients surviving an episode of peptic ulcer bleeding

PubMed Central

Ruigomez, A.; Rodriguez, L. A.; Hasselgren, G.; Johansson, S.; Wallander, M.

2000-01-01

STUDY OBJECTIVE—The authors investigated whether patients who have survived an acute episode of peptic ulcer bleeding (PUB) have an excess long term all cause mortality compared with the general population free of PUB.
DESIGN—Follow up study of previously identified cohort of patients with a PUB episode and a general population cohort.
SETTING—The source population included all people aged 30 to 89 years, registered with general practitioners in the United Kingdom.
PATIENTS—All patients alive one month after the PUB episode constituted the cohort of PUB patients (n=978). A control group of 5000 people was randomly sampled from the source population. The same eligibility criteria as for patients with PUB were applied to the control series. Also, controls had to be free of PUB before start date.
MAIN RESULTS—Relative risk of mortality among PUB patients was 2.1, 95%CI: 1.7, 2.6) compared with the general population. This increased mortality risk occurred mainly in the patients less than 60 years old. No difference was observed between men and women. The excess mortality was not only circumscribed to deaths attributable to recurrent gastrointestinal bleed, but also cardiovascular, cancer and other causes.
CONCLUSIONS—People who have survived an acute episode of PUB have a reduced long term survival compared with the general population.This reduction was stronger among middle age patients than in the elderly.


Keywords: cohort study; mortality; peptic ulcer; bleeding; population-based study PMID:10715746

Cancer Incidence in Physicians: A Taiwan National Population-based Cohort Study.

PubMed

Lee, Yu-Sung; Hsu, Chien-Chin; Weng, Shih-Feng; Lin, Hung-Jung; Wang, Jhi-Joung; Su, Shih-Bin; Huang, Chien-Cheng; Guo, How-Ran

2015-11-01

Cancer has been the leading cause of death in Taiwan since 1982. Physicians have many health-related risk factors which may contribute to cancer, such as rotating night shift, radiation, poor lifestyle, and higher exposure risk to infection and potential carcinogenic drugs. However, the cancer risk in physicians is not clear. In Taiwan's National Health Insurance Research Database, we identified 14,889 physicians as the study cohort and randomly selected 29,778 nonmedical staff patients as the comparison cohort for this national population-based cohort study. Cox proportional-hazard regression was used to compare the cancer risk between physicians and comparisons. Physician subgroups were also analyzed. Physicians had a lower all-cancer risk than did the comparisons (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.76-0.97). In the sex-based analysis, male physicians had a lower all-cancer risk than did male comparisons (HR 0.82, 95% CI 0.73-0.94); and female physicians did not (HR 1.29, 95% CI 0.88-1.91). In the cancer-type analysis, male physicians had a higher risk of prostate cancer (HR 1.72, 95% CI 1.12-2.65) and female physicians had twice the risk of breast cancer (HR 2.00, 95% CI 1.11-3.62) than did comparisons. Cancer risk was not significantly associated with physician specialties. Physicians in Taiwan had a lower all-cancer risk but higher risks for prostate and breast cancer than did the general population. These new epidemiological findings require additional study to clarify possible mechanisms.

Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects.

PubMed

Vakkalagadda, Blisse; Vetter, Marion L; Rana, Jignasa; Smith, Charles H; Huang, Jian; Karkas, Jennifer; Boulton, David W; LaCreta, Frank

2015-12-01

Saxagliptin and dapagliflozin are individually indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed-dose combination (FDC) tablets compared with coadministration of the individual tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs were evaluated in this open-label, randomized, single-dose crossover study. Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg + dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2). Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus individual components was concluded if the 90% CIs for FDC to individual component geometric mean ratios of C max, AUC 0-T, and AUC inf of both analytes were between 0.80 and 1.25. Seventy-two subjects were randomized; 71 (98.6%) completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets were bioequivalent to the individual tablets administered concomitantly. Food had no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to coadministration of the individual components in healthy subjects under fasted conditions and food had no clinically meaningful effect on bioavailability.

All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study.

PubMed

Schlenk, Richard F; Lübbert, Michael; Benner, Axel; Lamparter, Alexander; Krauter, Jürgen; Herr, Wolfgang; Martin, Hans; Salih, Helmut R; Kündgen, Andrea; Horst, Heinz-A; Brossart, Peter; Götze, Katharina; Nachbaur, David; Wattad, Mohammed; Köhne, Claus-Henning; Fiedler, Walter; Bentz, Martin; Wulf, Gerald; Held, Gerhard; Hertenstein, Bernd; Salwender, Hans; Gaidzik, Verena I; Schlegelberger, Brigitte; Weber, Daniela; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut

2016-12-01

The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m 2 , days 6-8; 15 mg/m 2 , days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).

Pharmacokinetics of oral sitamaquine taken with or without food and safety and efficacy for treatment of visceral leishmaniais: a randomized study in Bihar, India.

PubMed

Sundar, Shyam; Sinha, Prabhat K; Dixon, Susan A; Buckley, Renata; Miller, Ann K; Mohamed, Khadeeja; Al-Banna, Mahir

2011-06-01

This randomized, open-label study of patients in India with visceral leishmaniasis (VL) investigated the effect of food on sitamaquine and desethyl-sitamaquine pharmacokinetics. Patients were randomized to receive oral sitamaquine, 2 mg/kg/day, once a day for 21 days across four cohorts (n = 41) (fasted/fed, fed/fasted, fed/fed, and fasted/fasted) over two periods (days 1-10 and 11-21), or intravenous amphotericin B (AmB), 1 mg/kg every other day for 30 days (n = 20). Mean day 21 pharmacokinetics across the four cohorts were sitamaquine, area under curve (AUC)((0-τ)) = 6,627-8,903 ng.hr/mL, AUC((0-16)) = 4,859-6,633 ng.hr/mL, maximum plasma concentration (C(max)) = 401-570 ng/mL, apparent terminal half-life (t(1/2)) = 18.3-22.8 hr, time to reach C(max) (t(max)) = 3.5-6 hr; and desethyl-sitamaquine, AUC((0-τ)) = 2,307-3,163 ng.hr/mL, C(max) = 109-154 ng/mL, t(1/2) = 23.0-27.9 hr, t(max) = 2-10 hr, with no significant food effect. On-therapy adverse events were observed for sitamaquine in 4 (10%) of 41 patients and for AmB in 17 (85%) of 20 patients. The final clinical cure (day 180) was 85% (95% confidence interval = 70.8-94.4%) for sitamaquine and 95% (95% confidence interval = 75.1-99.9) for AmB. Sitamaquine can be taken regardless of food intake, was generally well tolerated, and showed potential efficacy in patients with visceral leishmaniasis.

Effect of Eischens Yoga During Radiation Therapy on Prostate Cancer Patient Symptoms and Quality of Life: A Randomized Phase II Trial.

PubMed

Ben-Josef, Avital Mazar; Chen, Jerry; Wileyto, Paul; Doucette, Abigail; Bekelman, Justin; Christodouleas, John; Deville, Curtiland; Vapiwala, Neha

2017-08-01

A randomized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue, erectile dysfunction, urinary incontinence, and overall quality of life (QOL) in prostate cancer (PCa) patients undergoing external beam radiation therapy (RT). The participants were randomized to yoga and no-yoga cohorts (1:1). Twice-weekly yoga interventions were offered throughout the 6- to 9-week courses of RT. Comparisons of standardized assessments were performed between the 2 cohorts for the primary endpoint of fatigue and the secondary endpoints of erectile dysfunction, urinary incontinence, and QOL before, during, and after RT. From October 2014 to January 2016, 68 eligible PCa patients underwent informed consent and agreed to participate in the study. Of the 68 patients, 18 withdrew early, mostly because of treatment schedule-related time constraints, resulting in 22 and 28 patients in the yoga and no-yoga groups, respectively. Throughout treatment, those in the yoga arm reported less fatigue than those in the control arm, with global fatigue, effect of fatigue, and severity of fatigue subscales showing statistically significant interactions (P<.0001). The sexual health scores (International Index of Erectile Function Questionnaire) also displayed a statistically significant interaction (P=.0333). The International Prostate Symptom Score revealed a statistically significant effect of time (P<.0001) but no significant effect of treatment (P=.1022). The QOL measures had mixed results, with yoga having a significant time by treatment effect on the emotional, physical, and social scores but not on functional scores. A structured yoga intervention of twice-weekly classes during a course of RT was associated with a significant reduction in pre-existing and RT-related fatigue and urinary and sexual dysfunction in PCa patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Loop diuretics for chronic heart failure: a foe in disguise of a friend?

PubMed

Kapelios, Chris J; Malliaras, Konstantinos; Kaldara, Elisabeth; Vakrou, Stella; Nanas, John N

2018-01-01

Loop diuretics are recommended for relieving symptoms and signs of congestion in patients with chronic heart failure and are administered to more than 80% of them. However, several of their effects have not systematically been studied. Numerous cohort and four interventional studies have addressed the effect of diuretics on renal function; apart from one prospective study, which showed that diuretics withdrawal is accompanied by increase in some markers of early-detected renal injury, all others converge to the conclusion that diuretics receipt, especially in high doses is associated with increased rates of renal dysfunction. Although a long standing perception has attributed a beneficial effect to diuretics in the setting of chronic heart failure, many cohort studies support that their use, especially in high doses is associated with adverse outcome. Several studies have used propensity scores in order to match diuretic and non-diuretic receiving patients; their results reinforce the notion that diuretics use and high diuretics dose are true risk factors and not disease severity markers, as some have suggested. One small, randomized study has demonstrated that diuretics decrease is feasible and safe and accompanied by a better prognosis. In conclusion, until elegantly designed, randomized trials, powered for clinical endpoints answer the unsettled issues in the field, the use of diuretics in chronic heart failure will remain subject to physicians' preferences and biases and not evidence based. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Parkinson disease and musculoskeletal pain: an 8-year population-based cohort study.

PubMed

Lien, Wei-Hung; Lien, Wei-Chih; Kuan, Ta-Shen; Wu, Shang-Te; Chen, Yi-Ting; Chiu, Ching-Ju

2017-07-01

The aim of this study was to evaluate the incidence and clinical features of musculoskeletal pain (MSP) in patients with Parkinson disease (PD) compared with a control group without the disease. The retrospective cohort study used a subset of the Taiwan National Health Insurance Research Database (NHIRD) comprising information on 1 million beneficiaries randomly sampled from the entire population of Taiwan. A total of 490 patients aged 50 and above with newly diagnosed Parkinson disease were identified during a period from 2000 to 2005. Among them, 199 developed MSP after PD. The control group consisted of 1960 participants without PD over the study period randomly selected by matching PD cases according to the date of PD incidence, age, and sex. The study groups were then followed to the end of 2007. Musculoskeletal pain was the end point. The incidence rate ratios of MSP were higher in the PD group than in the control group, representing an adjusted hazard ratio of 1.31 (95% confidence interval 1.09 to 1.58). PD was associated with a significantly elevated risk of MSP in all sex and age stratifications, with the highest hazard ratio noted for middle-aged male patients with PD, followed by older male patients with PD. This study showed that the PD may significantly increase the risk of developing MSP. The risk of developing MSP seems to be greatest for middle-aged male patients with PD. Clinicians should be more alert for MSP in patients with PD, and early intervention should be considered.

A systematic review on the relations between pasta consumption and cardio-metabolic risk factors.

PubMed

Huang, M; Li, J; Ha, M-A; Riccardi, G; Liu, S

2017-11-01

The traditional Italian dish pasta is a major food source of starch with low glycemic index (GI) and an important low-GI component of the Mediterranean diet. This systematic review aimed at assessing comprehensively and in-depth the potential benefit of pasta on cardio-metabolic disease risk factors. Following a standard protocol, we conducted a systematic literature search of PubMed, CINAHL, and Cochrane Central Register of Controlled Trials for prospective cohort studies and randomized controlled dietary intervention trials that examined pasta and pasta-related fiber and grain intake in relation to cardio-metabolic risk factors of interest. Studies comparing postprandial glucose response to pasta with that to bread or potato were quantitatively summarized using meta-analysis of standardized mean difference. Evidence from studies with pasta as part of low-GI dietary intervention and studies investigating different types of pasta were qualitatively summarized. Pasta meals have significantly lower postprandial glucose response than bread or potato meals, but evidence was lacking in terms of how the intake of pasta can influence cardio-metabolic disease risk. More long-term randomized controlled trials are needed where investigators directly contrast the cardio-metabolic effects of pasta and bread or potato. Long-term prospective cohort studies with required data available should also be analyzed regarding the effect of pasta intake on disease endpoints. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.

PubMed

Merhi, Basma; Shireman, Theresa; Carpenter, Myra A; Kusek, John W; Jacques, Paul; Pfeffer, Marc; Rao, Madhumathi; Foster, Meredith C; Kim, S Joseph; Pesavento, Todd E; Smith, Stephen R; Kew, Clifton E; House, Andrew A; Gohh, Reginald; Weiner, Daniel E; Levey, Andrew S; Ix, Joachim H; Bostom, Andrew

2017-09-01

Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality. Cohort study. The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs. Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization. During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92-1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15-1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04-1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00-1.31), transplant failure (HR, 1.72; 95% CI, 1.46-2.01), and mortality (HR, 1.34; 95% CI, 1.15-1.54). We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites. Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted. Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.

A randomized trial comparing concise and standard consent forms in the START trial

PubMed Central

Touloumi, Giota; Walker, A. Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G.; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

2017-01-01

Background Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. Methods We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). Results 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. Conclusions An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Trial registration Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12 PMID:28445471

Reporting clinical outcomes of breast reconstruction: a systematic review.

PubMed

Potter, S; Brigic, A; Whiting, P F; Cawthorn, S J; Avery, K N L; Donovan, J L; Blazeby, J M

2011-01-05

Breast reconstruction after mastectomy for cancer requires accurate evaluation to inform evidence-based participatory decision making, but the standards of outcome reporting after breast reconstruction have not previously been considered. We used extensive searches to identify articles reporting surgical outcomes of breast reconstruction. We extracted data using published criteria for complication reporting modified to reflect reconstructive practice. Study designs included randomized controlled trials, cohort studies, and case series. The Cochrane Risk of Bias tool was used to critically appraise all study designs. Other criteria used to assess the studies were selection and funding bias, statistical power calculations, and institutional review board approval. Wilcoxon signed rank tests were used to compare the breadth and frequency of study outcomes, and χ² tests were used to compare the number of studies in each group reporting each of the published criteria. All statistical tests were two-sided. Surgical complications following breast reconstruction in 42,146 women were evaluated in 134 studies. These included 11 (8.2%) randomized trials, 74 (55.2%) cohort studies, and 49 (36.6%) case series. Fifty-three percent of studies demonstrated a disparity between methods and results in the numbers of complications reported. Complications were defined by 87 (64.9%) studies and graded by 78 (58.2%). Details such as the duration of follow-up and risk factors for adverse outcomes were omitted from 47 (35.1%) and 58 (43.3%) studies, respectively. Overall, the studies defined fewer than 20% of the complications they reported, and the definitions were largely inconsistent. The results of this systematic review suggest that outcome reporting in breast reconstruction is inconsistent and lacks methodological rigor. The development of a standardized core outcome set is recommended to improve outcome reporting in breast reconstruction.

Enoxaparin is superior to unfractionated heparin in patients with ST elevation myocardial infarction undergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis.

PubMed

Giraldez, Roberto R; Nicolau, José Carlos; Corbalan, Ramon; Gurfinkel, Enrique P; Juarez, Ursulo; Lopez-Sendon, Jose; Parkhomenko, Alexander; Molhoek, Peter; Mohanavelu, Satishkumar; Morrow, David A; Antman, Elliott M

2007-07-01

We compared outcomes of ST-elevation myocardial infarction (STEMI) patients randomized to a strategy of either enoxaparin or unfractionated heparin (UFH) to support fibrinolysis. In the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction Study 25 (ExTRACT-TIMI 25) trial, 20,479 patients undergoing fibrinolysis for STEMI with a fibrin-specific agent (N = 16,283) or streptokinase (SK) (N = 4139) were randomized to enoxaparin throughout their hospitalization or UFH for at least 48 h. The primary end point of death or nonfatal recurrent MI through 30 days occurred in 12.0% of patients in the UFH and 9.8% in the enoxaparin groups when treated with fibrin-specific lytics [odds ratio(adjusted) (OR(adj)) 0.78; 95% CI 0.70-0.87; P < 0.001] and 11.8 vs. 10.2%, respectively, when treated with SK (OR(adj) 0.83; 95% CI 0.66-1.04; P = 0.10; P(interaction) = 0.58). Major bleeding rates including intracranial hemorrhage within the fibrin-specific cohort were 1.2 and 2.0% in the UFH and enoxaparin groups, respectively (P < 0.001) and 2.0% in UFH and 2.4% in enoxaparin patients in the SK cohort (P = 0.16). Interaction tests between antithrombin- and lytic-type were non-significant (P = 0.20). Death, nonfatal MI, or major bleeding was significantly reduced with enoxaparin in the fibrin-specific cohort (OR(adj) 0.82; 95% CI 0.74-0.91; P < 0.001) and favoured enoxaparin in the SK cohort (OR(adj) 0.89; 95% CI 0.72-1.10; P = 0.29; P(interaction) = 0.53). The benefits of an enoxaparin strategy over UFH were observed in both SK and fibrin-specific-treated STEMI patients. Therefore, an enoxaparin strategy is preferred over UFH to support fibrinolysis for STEMI regardless of lytic agent.

LD-aminopterin in the canine homologue of human atopic dermatitis: a randomized, controlled trial reveals dosing factors affecting optimal therapy.

PubMed

Zebala, John A; Mundell, Alan; Messinger, Linda; Griffin, Craig E; Schuler, Aaron D; Kahn, Stuart J

2014-01-01

Options are limited for patients with atopic dermatitis (AD) who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD. This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg) or twice-weekly (0.007 mg/kg) LD-aminopterin. The primary efficacy outcome was the Global Score (GS), a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01). The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo. Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD.

LD-Aminopterin in the Canine Homologue of Human Atopic Dermatitis: A Randomized, Controlled Trial Reveals Dosing Factors Affecting Optimal Therapy

PubMed Central

Zebala, John A.; Mundell, Alan; Messinger, Linda; Griffin, Craig E.; Schuler, Aaron D.; Kahn, Stuart J.

2014-01-01

Background Options are limited for patients with atopic dermatitis (AD) who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD. Methods and Findings This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg) or twice-weekly (0.007 mg/kg) LD-aminopterin. The primary efficacy outcome was the Global Score (GS), a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01). The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo. Conclusions Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD. PMID:25255447

Association of coffee consumption with risk of colorectal cancer: a meta-analysis of prospective cohort studies.

PubMed

Gan, Yong; Wu, Jiang; Zhang, Shengchao; Li, Liqing; Cao, Shiyi; Mkandawire, Naomie; Ji, Kun; Herath, Chulani; Gao, Chao; Xu, Hong; Zhou, Yanfeng; Song, Xingyue; Chen, Shanquan; Chen, Yawen; Yang, Tingting; Li, Jing; Qiao, Yan; Hu, Sai; Yin, Xiaoxv; Lu, Zuxun

2017-03-21

A meta-analysis was performed to assess the association of coffee consumption with colorectal cancer and to investigate the shape of the association. Relevant prospective cohort studies were identified by a comprehensive search of the PubMed, Embase and Web of Science databases from their inception through August 2015. Either a random-effects model or fixed-effects model was used to compute the pooled risk estimates when appropriate. Linear and nonlinear dose-response meta-analyses were also performed. Nineteen prospective cohort studies involving 2,046,575 participants and 22,629 patients with colorectal cancer were included. The risk of colon cancer was decreased by 7% for every 4 cups per day of coffee (RR=0.93, 95%CI, 0.88-0.99; P=0.199). There was a threshold approximately five cups of coffee per day, and the inverse association for colorectal cancer appeared to be stronger at a higher range of intake. However, a nonlinear association of rectal cancer with coffee consumption was not observed (P for nonlinearity = 0.214). In conclusion, coffee consumption is significantly associated with a decreased risk of colorectal cancer at ≥ 5 cups per day of coffee consumption. The findings support the recommendations of including coffee as a healthy beverage for the prevention of colorectal cancer.

Association of coffee consumption with risk of colorectal cancer: a meta-analysis of prospective cohort studies

PubMed Central

Zhang, Shengchao; Li, Liqing; Cao, Shiyi; Mkandawire, Naomie; Ji, Kun; Herath, Chulani; Gao, Chao; Xu, Hong; Zhou, Yanfeng; Song, Xingyue; Chen, Shanquan; Chen, Yawen; Yang, Tingting; Li, Jing; Qiao, Yan; Hu, Sai; Yin, Xiaoxv; Lu, Zuxun

2017-01-01

A meta-analysis was performed to assess the association of coffee consumption with colorectal cancer and to investigate the shape of the association. Relevant prospective cohort studies were identified by a comprehensive search of the PubMed, Embase and Web of Science databases from their inception through August 2015. Either a random-effects model or fixed-effects model was used to compute the pooled risk estimates when appropriate. Linear and nonlinear dose-response meta-analyses were also performed. Nineteen prospective cohort studies involving 2,046,575 participants and 22,629 patients with colorectal cancer were included. The risk of colon cancer was decreased by 7% for every 4 cups per day of coffee (RR=0.93, 95%CI, 0.88-0.99; P=0.199). There was a threshold approximately five cups of coffee per day, and the inverse association for colorectal cancer appeared to be stronger at a higher range of intake. However, a nonlinear association of rectal cancer with coffee consumption was not observed (P for nonlinearity = 0.214). In conclusion, coffee consumption is significantly associated with a decreased risk of colorectal cancer at ≥ 5 cups per day of coffee consumption. The findings support the recommendations of including coffee as a healthy beverage for the prevention of colorectal cancer. PMID:27078843

Educational Differences in U.S. Adult Mortality: A Cohort Perspective*

PubMed Central

Masters, Ryan K.; Hummer, Robert A.; Powers, Daniel A.

2014-01-01

We use hierarchical cross-classified random-effects models to simultaneously measure age, period, and cohort patterns of mortality risk between 1986 and 2006 for non-Hispanic white and non-Hispanic black men and women with less than a high school education, a high school education, and more than a high school education. We examine all-cause mortality risk and mortality risk from heart disease, lung cancer, and unpreventable cancers. Findings reveal that temporal reductions in black and white men’s and women’s mortality rates were driven entirely by cohort changes in mortality. Findings also demonstrate that disparate cohort effects between education groups widened the education gap in all-cause mortality risk and mortality risk from heart disease and lung cancer across this time period. Educational disparities in mortality risk from unpreventable cancers, however, did not change. This research uncovers widening educational differences in adult mortality and demonstrates that a cohort perspective provides valuable insights for understanding recent temporal changes in U.S. mortality risk. PMID:25346542

Vitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study.

PubMed

Molloy, J; Koplin, J J; Allen, K J; Tang, M L K; Collier, F; Carlin, J B; Saffery, R; Burgner, D; Ranganathan, S; Dwyer, T; Ward, A C; Moreno-Betancur, M; Clarke, M; Ponsonby, A L; Vuillermin, P

2017-08-01

Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D 3 (25(OH)D 3 ) levels among infants with food allergy vs a random subcohort (n = 274). The primary exposures were VDI (25(OH)D 3 <50 nM) at birth and 6 months of age. Ambient UVR and time in the sun were combined to estimate UVR exposure dose. IgE-mediated food allergy status at 1 year was determined by formal challenge. Binomial regression was used to examine associations between VDI, UVR exposure dose and food allergy and investigate potential confounding. Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blood pressure and stroke: an overview of published reviews.

PubMed

Lawes, Carlene M M; Bennett, Derrick A; Feigin, Valery L; Rodgers, Anthony

2004-03-01

The last few years have seen a considerable increase in the amount of information available concerning blood pressure (BP) and stroke associations. This article provides an overview of published reviews of the effects on stroke seen in trials of BP-lowering drugs and compares these with the results available from cohort studies. We present a review of major overviews of prospective cohort studies and an updated meta-analysis of >40 randomized controlled trials of BP lowering, which included >188 000 participants and approximately 6800 stroke events. Cohort studies now indicate that in the Asia Pacific region as well as in North America and Western Europe, each 10 mm Hg lower systolic BP is associated with a decrease in risk of approximately one third in subjects aged 60 to 79 years. The association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, and stroke subtypes and for fatal and nonfatal events. The proportional association is age dependent but is still a strong and positive association in those aged 80 years. Data from randomized controlled trials, in which mean age at event was approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is associated with a reduction in risk of stroke of approximately one third. Per mm Hg systolic BP reduction, the benefits for stroke appear similar between agents, by baseline BP levels, and whether or not individuals have a past history of cardiovascular disease. There is, however, evidence of greater benefit with a larger BP reduction. The epidemiologically expected benefits of BP lowering for stroke risk reduction are broadly consistent across a range of different population subgroups. There are greater benefits from larger BP reductions, and initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.

Blood pressure and stroke: an overview of published reviews.

PubMed

Lawes, Carlene M M; Bennett, Derrick A; Feigin, Valery L; Rodgers, Anthony

2004-04-01

The last few years have seen a considerable increase in the amount of information available concerning blood pressure (BP) and stroke associations. This article provides an overview of published reviews of the effects on stroke seen in trials of BP-lowering drugs and compares these with the results available from cohort studies. We present a review of major overviews of prospective cohort studies and an updated meta-analysis of >40 randomized controlled trials of BP lowering, which included >188 000 participants and approximately 6800 stroke events. Cohort studies now indicate that in the Asia Pacific region as well as in North America and Western Europe, each 10 mm Hg lower systolic BP is associated with a decrease in risk of stroke of approximately one third in subjects aged 60 to 79 years. The association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, and stroke subtypes and for fatal and nonfatal events. The proportional association is age dependent but is still strong and positive in those aged 80 years. Data from randomized controlled trials, in which mean age at event was approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is associated with a reduction in risk of stroke of approximately one third. Per mm Hg systolic BP reduction, the relative benefits for stroke appear similar between agents, by baseline BP levels, and whether or not individuals have a past history of cardiovascular disease. There is, however, evidence of greater benefit with a larger BP reduction. The epidemiologically expected benefits of BP lowering for stroke risk reduction are broadly consistent across a range of different population subgroups. There are greater benefits from larger BP reductions, and initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.

Prescription pattern of Chinese herbal products for heart failure in Taiwan: A population-based study.

PubMed

Tsai, Ming-Yen; Hu, Wen-Long; Lin, Che-Chen; Lee, Yi-Chiao; Chen, Shih-Yu; Hung, Yu-Chiang; Chen, Yung-Hsiang

2017-02-01

Certain Chinese herbal products (CHPs) may protect against the progression of heart failure (HF). However, there is a lack of research regarding the use of CHPs in patients with HF. The aims of this study were to analyze CHPs usage patterns in patients with HF and to identify the frequency and combination of CHPs most commonly used for HF. This retrospective, nationwide, population-based cohort study was conducted using a randomly sampled cohort of one million patients selected from the National Health Insurance Research Database (NHIRD) for the years 2000-2010 in Taiwan. CHP use and the top ten most frequently prescribed formulae and single herbs for treating HF were assessed, including total formulae number and average and frequency of prescriptions. Demographic characteristics, including sex and age at diagnosis of HF, were examined, together with existing comorbidities. The cohort included 19,988 newly diagnosed AD patients, who were given CHP treatment for HF between 2000 and 2010. Among them, female patients (53.3%) and those over 65years old (63.9%) were more likely to use CM. After adjusting for demographic factors, HF patients suffering from coronary artery disease (CAD) were more likely to seek traditional Chinese medicine (TCM) treatment than those with non-TCM users (57.6% vs. 52.6%). Zhi-Gan-Cao-Tang (4.07%) and Danshen (5.13%) were the most frequent formula CHP and single CHP prescribed by TCM practitioners for treating HF, respectively. Most people with HF who consumed CHPs used CHPs to supplement Yang-Qi, nourish the Ying-blood, and strengthen the heart spirit as complementary medicines to relieve HF-related symptoms, in addition to using standard anti-HF treatments. Further large-scale, randomized clinical trials are warranted in order to determine the effectiveness and safety of these herbal medicines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Psychometric evaluation of the Chinese version of the Subjective Happiness Scale: evidence from the Hong Kong FAMILY Cohort.

PubMed

Nan, Hairong; Ni, Michael Y; Lee, Paul H; Tam, Wilson W S; Lam, Tai Hing; Leung, Gabriel M; McDowell, Ian

2014-08-01

With China's rapid economic growth in the past few decades, there is currently an emerging focus on happiness. Cross-cultural validity studies have indicated that the four-item Subjective Happiness Scale (SHS) has high internal consistency and stable reliability. However, the psychometric characteristics of the SHS in broader Chinese community samples are unknown. We evaluated the factor structure and psychometric properties of the SHS in the Hong Kong general population. The Chinese SHS was derived using forward-backward translation. Of the Cantonese-speaking participants aged ≥15 years, 2,635 were randomly selected from the random sample component of the FAMILY Cohort, a territory-wide cohort study in Hong Kong. In addition to the SHS, a single-item overall happiness scale, the Patient Health Questionnaire-9 (PHQ-9), the Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR) scale, and the Medical Outcomes Study 12-item short-form version 2 (SF-12) mental and physical health scales were administered. Exploratory and confirmatory factor analyses supported a single factor with high loadings for the four SHS items. Multiple group analyses indicated factor invariance across sex and age groups. Cronbach's alpha was 0.82, and 2-week test-retest reliability (n = 191) was 0.70. The SHS correlated significantly with single-item overall happiness (Spearman's rho [ρ] = 0.57), Family APGAR (ρ = 0.26), PHQ-9 (ρ = -0.34), and mental health-related quality of life (ρ = 0.40) but showed a lower correlation with physical health (ρ = 0.15). A regression model that included the PHQ-9 and Family APGAR scores explained 37% of the variance in SF-12 mental health scores; adding the SHS raised the variance explained to 41 %. Our results support the reliability and validity of the SHS as a relevant component in the measurement battery for mental well-being in a Chinese general population.

Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case-control study in the Danish National Birth Cohort.

PubMed

Liew, Zeyan; Ritz, Beate; von Ehrenstein, Ondine S; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Fei, Chunyuan; Bossi, Rossana; Henriksen, Tine Brink; Bonefeld-Jørgensen, Eva Cecilie; Olsen, Jørn

2015-04-01

Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited. We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children. Among 83,389 mother-child pairs enrolled in the Danish National Birth Cohort during 1996-2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child's sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother's PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise. In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children.

The Nottingham study of neurotic disorder: predictors of 12 year costs.

PubMed

Knerer, G; Byford, S; Johnson, T; Seivewright, H; Tyrer, P

2005-09-01

To examine the relationship between clinical, demographic and socio-economic characteristics and the long-term costs of a cohort of neurotic patients. Analysis of the costs of a cohort of 210 people entered in the Nottingham study of neurotic disorders, a randomized controlled evaluation of five treatments for neurotic disorders. Service use data were collected at 5 and 12 years after study entry. Multiple regression analyses were conducted. The total cost per patient over the 12-year follow-up period was calculated to be $11,940 (SD $15,520) ( pound7450, SD pound9690). Higher costs were significantly associated with the presence of general neurotic syndrome, an initial diagnosis of dysthymia and a recurrent episode of illness. The total costs of care for a range of neurotic disorders are broadly comparable with other estimates of costs reported in the literature for similar populations. Those responsible for higher costs in the longer-term have comorbid anxiety, depressive and personality disorders. Copyright (c) 2005 Blackwell Munksgaard

Parental separation and pediatric cancer: a Danish cohort study.

PubMed

Grant, Sally; Carlsen, Kathrine; Bidstrup, Pernille Envold; Bastian, Gro Samsø; Lund, Lasse Wegener; Dalton, Susanne Oksbjerg; Johansen, Christoffer

2012-05-01

The purpose of this study was to determine the risk for separation (ending cohabitation) of the parents of a child with a diagnosis of cancer. In a nationwide cohort, we compared the risk for ending cohabitation of the parents of 2450 children (aged 0-20 years) given a diagnosis of cancer with the risk of parents of 44 853 randomly selected, gender- and age-matched cancer-free children. We adjusted for socioeconomic position and demographic factors. Rate ratios and 95% confidence intervals for separation were estimated in a Cox proportional hazards model. The parents of children with cancer did not have a higher risk for separation than the general population (rate ratio: 1.00 [95% confidence interval: 0.91-1.10]). Separate analyses according to type of cancer and survival of the child similarly yielded null results. Experiencing cancer in a child does not seem to be a risk factor for separation. Our study will allow clinicians to reassure parents and to support them in facing the trauma of cancer in their child.

Explaining mortality rate plateaus

PubMed Central

Weitz, Joshua S.; Fraser, Hunter B.

2001-01-01

We propose a stochastic model of aging to explain deviations from exponential growth in mortality rates commonly observed in empirical studies. Mortality rate plateaus are explained as a generic consequence of considering death in terms of first passage times for processes undergoing a random walk with drift. Simulations of populations with age-dependent distributions of viabilities agree with a wide array of experimental results. The influence of cohort size is well accounted for by the stochastic nature of the model. PMID:11752476

Insomnia and the risk of depression: a meta-analysis of prospective cohort studies.

PubMed

Li, Liqing; Wu, Chunmei; Gan, Yong; Qu, Xianguo; Lu, Zuxun

2016-11-05

Observational studies suggest that insomnia might be associated with an increased risk of depression with inconsistent results. This study aimed at conducting a meta-analysis of prospective cohort studies to evaluate the association between insomnia and the risk of depression. Relevant cohort studies were comprehensively searched from the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases (up to October 2014) and from the reference lists of retrieved articles. A random-effects model was used to calculate the pooled risk estimates and 95 % confidence intervals (CIs). The I 2 statistic was used to assess the heterogeneity and potential sources of heterogeneity were assessed with meta-regression. The potential publication bias was explored by using funnel plots, Egger's test, and Duval and Tweedie trim-and-fill methods. Thirty-four cohort studies involving 172,077 participants were included in this meta-analysis with an average follow-up period of 60.4 months (ranging from 3.5 to 408). Statistical analysis suggested a positive relationship between insomnia and depression, the pooled RR was 2.27 (95 % CI: 1.89-2.71), and a high heterogeneity was observed (I 2  = 92.6 %, P < 0.001). Visual inspection of the funnel plot revealed some asymmetry. The Egger's test identified evidence of substantial publication bias (P <0.05), but correction for this bias using trim-and-fill method did not alter the combined risk estimates. This meta-analysis indicates that insomnia is significantly associated with an increased risk of depression, which has implications for the prevention of depression in non-depressed individuals with insomnia symptoms.

Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants.

PubMed

Zhou, Ang; Taylor, Amy E; Karhunen, Ville; Zhan, Yiqiang; Rovio, Suvi P; Lahti, Jari; Sjögren, Per; Byberg, Liisa; Lyall, Donald M; Auvinen, Juha; Lehtimäki, Terho; Kähönen, Mika; Hutri-Kähönen, Nina; Perälä, Mia Maria; Michaëlsson, Karl; Mahajan, Anubha; Lind, Lars; Power, Chris; Eriksson, Johan G; Raitakari, Olli T; Hägg, Sara; Pedersen, Nancy L; Veijola, Juha; Järvelin, Marjo-Riitta; Munafò, Marcus R; Ingelsson, Erik; Llewellyn, David J; Hyppönen, Elina

2018-05-14

Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (β = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; β = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (P heterogeneity  > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

Impact of Study Design on Reported Incidences of Acute Mountain Sickness: A Systematic Review.

PubMed

Waeber, Baptiste; Kayser, Bengt; Dumont, Lionel; Lysakowski, Christopher; Tramèr, Martin R; Elia, Nadia

2015-09-01

Published incidences of acute mountain sickness (AMS) vary widely. Reasons for this variation, and predictive factors of AMS, are not well understood. We aimed to identify predictive factors that are associated with the occurrence of AMS, and to test the hypothesis that study design is an independent predictive factor of AMS incidence. We did a systematic search (Medline, bibliographies) for relevant articles in English or French, up to April 28, 2013. Studies of any design reporting on AMS incidence in humans without prophylaxis were selected. Data on incidence and potential predictive factors were extracted by two reviewers and crosschecked by four reviewers. Associations between predictive factors and AMS incidence were sought through bivariate and multivariate analyses for different study designs separately. Association between AMS incidence and study design was assessed using multiple linear regression. We extracted data from 53,603 subjects from 34 randomized controlled trials, 44 cohort studies, and 33 cross-sectional studies. In randomized trials, the median of AMS incidences without prophylaxis was 60% (range, 16%-100%); mode of ascent and population were significantly associated with AMS incidence. In cohort studies, the median of AMS incidences was 51% (0%-100%); geographical location was significantly associated with AMS incidence. In cross-sectional studies, the median of AMS incidences was 32% (0%-68%); mode of ascent and maximum altitude were significantly associated with AMS incidence. In a multivariate analysis, study design (p=0.012), mode of ascent (p=0.003), maximum altitude (p<0.001), population (p=0.002), and geographical location (p<0.001) were significantly associated with AMS incidence. Age, sex, speed of ascent, duration of exposure, or history of AMS were inconsistently reported and therefore not further analyzed. Reported incidences and identifiable predictive factors of AMS depend on study design.

Genetic anticipation in BRCA1/2 families after controlling for ascertainment bias and cohort effect

PubMed Central

Guindalini, Rodrigo Santa Cruz; Song, Andrew; Fackenthal, James D.; Olopade, Olufunmilayo I.; Huo, Dezheng

2016-01-01

Background Genetic anticipation, the earlier onset of disease in successive generations, has been reported in hereditary breast and ovarian cancer syndrome (HBOC), but little is known about its underlying mechanisms. Ascertainment bias is a reason that has been suggested in previous studies. Likewise, cohort effect, which may be due to environmental factors, can be misinterpreted as genetic anticipation. Methods We conducted a review of pedigrees in 176 kindreds segregating deleterious mutations in BRCA1/2 genes who had at least two consecutive generations of the same cancer (breast or ovarian). Using mutation probabilities as analytical weights in weighted random-effect models, we calculated generational differences in age of onset of breast/ovarian cancer. Then we further controlled for ascertainment bias by excluding probands and adjusted for birth cohort effect in the anticipation models. Results The mean age of breast cancer for the probands’ generation was 41.9 years, which was 6.8 years and 9.8 years earlier than the parents’ and grandparents’ generations, respectively. The anticipation effect for breast cancer remained significant after excluding probands. There was a birth cohort effect: patients born in 1930s and 1940s had breast cancer 5.0 and 7.6 years earlier than patients born before 1920. The difference in breast cancer age of onset across generations was no longer significant after adjusting for birth cohort effect. Conclusions The observed anticipation effect was mainly driven by a decrease in age of onset across birth cohorts, underscoring the need for risk reducing interventions that target changing environmental/lifestyle factors in BRCA1/2 carriers. PMID:26992017

Bladder cancer biomarker discovery using global metabolomic profiling of urine.

PubMed

Wittmann, Bryan M; Stirdivant, Steven M; Mitchell, Matthew W; Wulff, Jacob E; McDunn, Jonathan E; Li, Zhen; Dennis-Barrie, Aphrihl; Neri, Bruce P; Milburn, Michael V; Lotan, Yair; Wolfert, Robert L

2014-01-01

Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence after initial diagnosis and treatment. As a result, recurrent surveillance, primarily involving repeated cystoscopies, is a critical component of post diagnosis patient management. Since cystoscopy is invasive, expensive and a possible deterrent to patient compliance with regular follow-up screening, new non-invasive technologies to aid in the detection of recurrent and/or primary bladder cancer are strongly needed. In this study, mass spectrometry based metabolomics was employed to identify biochemical signatures in human urine that differentiate bladder cancer from non-cancer controls. Over 1000 distinct compounds were measured including 587 named compounds of known chemical identity. Initial biomarker identification was conducted using a 332 subject sample set of retrospective urine samples (cohort 1), which included 66 BCa positive samples. A set of 25 candidate biomarkers was selected based on statistical significance, fold difference and metabolic pathway coverage. The 25 candidate biomarkers were tested against an independent urine sample set (cohort 2) using random forest analysis, with palmitoyl sphingomyelin, lactate, adenosine and succinate providing the strongest predictive power for differentiating cohort 2 cancer from non-cancer urines. Cohort 2 metabolite profiling revealed additional metabolites, including arachidonate, that were higher in cohort 2 cancer vs. non-cancer controls, but were below quantitation limits in the cohort 1 profiling. Metabolites related to lipid metabolism may be especially interesting biomarkers. The results suggest that urine metabolites may provide a much needed non-invasive adjunct diagnostic to cystoscopy for detection of bladder cancer and recurrent disease management.

Sugar-Sweetened Beverages and Weight Gain in Children and Adults: A Systematic Review from 2013 to 2015 and a Comparison with Previous Studies

PubMed Central

Luger, Maria; Lafontan, Max; Bes-Rastrollo, Maira; Winzer, Eva; Yumuk, Volkan; Farpour-Lambert, Nathalie

2018-01-01

Objective Partly inconsistent findings from previous reviews have fueled discussions on the impact of sugar-sweetened beverages (SSBs) on obesity development. The aim was to systematically review the recent evidence in children and adults. Methods Data were retrieved from the databases MEDLINE, EMBASE, and Cochrane library for the period January 2013 to October 2015. A systematic review of prospective cohort studies and randomized controlled trials (RCTs) relating SSBs to weight measures was conducted. Results 30 publications met the inclusion criteria. Prospective cohort studies (96%; n = 26) showed a positive association between consumption of SSBs and weight/BMI in adults and children (n = 242,352), and only one cohort study in children showed no association. Findings from three RCTs in children demonstrated that SSB consumption had an effect on BMI/BMI z-score. The one RCT in adults showed no significant effect of the intervention. 63% of the studies were of good, 30% of medium quality, and none was funded by industry. Conclusion Recent evidence suggests that SSB consumption is positively associated with or has an effect on obesity indices in children and adults. By combining the already published evidence with the new one, we conclude that public health policies should aim to reduce the consumption of SSBs and encourage healthy alternatives such as water. PMID:29237159

Statins and Hip Fracture Prevention – A Population Based Cohort Study in Women

PubMed Central

Helin-Salmivaara, Arja; Korhonen, Maarit J.; Lehenkari, Petri; Junnila, Seppo Y. T.; Neuvonen, Pertti J.; Ruokoniemi, Päivi; Huupponen, Risto

2012-01-01

Objective To study the association of long-term statin use and the risk of low-energy hip fractures in middle-aged and elderly women. Design A register-based cohort study. Setting Finland. Participants Women aged 45–75 years initiating statin therapy between 1996 and 2001 with adherence to statins ≥80% during the subsequent five years (n = 40 254), a respective cohort initiating hypertension drugs (n = 41 610), and women randomly selected from the population (n = 62 585). Main Outcome Measures Incidence rate of and hazard ratio (HR) for low-energy hip fracture during the follow-up extending up to 7 years after the 5-year exposure period. Results Altogether 199 low-energy hip fractures occurred during the 135 330 person-years (py) of follow-up in the statin cohort, giving an incidence rate of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts, the rates were 2.0 per 1000 py (312 fractures per 157 090 py) and 1.0 per 1000 py (212 fractures per 216 329 py), respectively. Adjusting for a propensity score and individual variables strongly predicting the outcome, good adherence to statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58–0.86) of a low-energy hip fracture in comparison with adherent use of hypertension drugs. The association was of the same magnitude when comparing the statin users with the population cohort, the HR being 0.69 (0.55–0.87). When women with poor (<40%), moderate (40 to 80%), and good adherence (≥80%) to statins were compared to those with good adherence to hypertension drugs (≥80%) or to the population cohort, the protective effect associated with statin use attenuated with the decreasing level of adherence. Conclusions 5-year exposure to statins is associated with a reduced risk of low-energy hip fracture in women aged 50–80 years without prior hospitalizations for fractures. PMID:23144731

Red and processed meat consumption and risk of glioma in adults: A systematic review and meta-analysis of observational studies

PubMed Central

Saneei, Parvane; Willett, Walter; Esmaillzadeh, Ahmad

2015-01-01

Background: These findings from several observational studies, investigated the association between red meat consumption and gliomas, were inconsistent. We conducted a systematic review and meta-analysis of observational studies to summarize available date on the relation between meat intake and risk of glioma. Materials and Methods: A systematic literature search of relevant reports published until May 2014 of the PubMed/Medline, ISI Web of Knowledge, Excerpta Medica database, Ovid database, Google Scholar, and Scopus databases was conducted. From 723 articles yielded in the preliminary literature search, data from eighteen publications (14 case-control, three cohort, and one nested case-control study) on unprocessed red meat, processed meat, and/or total red meat consumption in relation to glioma in adults were included in the analysis. Quality assessment of studies was performed. Random effects model was used to conduct the meta-analysis. Results: We found a positive significant association between unprocessed red meat intake and risk of glioma (relative risk [RR] = 1.30; 95% confidence interval [CI]: 1.08-1.58) after excluding three studies with uncertain type of brain cancer. This analysis included only one cohort study which revealed no relation between unprocessed red meat intake and glioma (RR = 1.75; 95% CI: 0.35-8.77). Consumption of processed meats was not related to increased risk of glioma in population-based case-control studies (RR = 1.26; 95% CI: 1.05-1.51) and reduced risk in hospital-based case-controls (RR = 0.79; 95% CI: 0.65-0.97). No significant association was seen between processed red meat intake and risk of glioma in cohort studies (RR: 1.08; 95% CI: 0.84-1.37). Total red meat consumption was not associated with risk of adult glioma in case-control or cohort studies. Conclusion: In this meta-analysis of 18 observational studies, we found a modest positive association between unprocessed red meat intake and risk of gliomas based almost entirely on case-control studies. Processed red meat was overall not associated with risk of gliomas in case-control or cohort studies. PMID:26600837

Health-related quality of life in cancer patients at the end of life, translation, validation, and longitudinal analysis of specific tools: study protocol for a randomized controlled trial.

PubMed

Poirier, Anne-Lise; Kwiatkowski, Fabrice; Commer, Jean-Marie; D'Aillières, Bénédicte; Berger, Virginie; Mercier, Mariette; Bonnetain, Franck

2012-04-20

The end of life for cancer patients is the ultimate stage of the disease, and care in this setting is important as it can improve the wellbeing not only of patients, but also the patients' family and close friends. As it is a matter of profoundly personal concerns, patients' perception of this phase of the disease is difficult to assess and has thus been insufficiently studied. Nonetheless, caregivers are required to provide specific care to help patients and to treat them in order to improve their wellbeing during this period.While tools to assess health-related quality of life (QoL) in cancer patients at the end of life exist in English, to our knowledge, no validated tools are available in French. This randomized multicenter cohort study will be carried out to cross-culturally adapt and validate a French version of the English QUAL-E and the Missoula Vitas Quality Of Life Index (MVQOLI) questionnaires for advanced cancer patients in a palliative setting. A randomized clinical trial component in addition to a cohort study is implemented in order to test psychometric hypotheses: order effect and improvement of sensibility to change.The validation procedure will ensure that the psychometric properties are maintained.The main criterion to assess the reliability of the questionnaires will be reproducibility (test-retest method) using intraclass correlation coefficients. It will be necessary to include 372 patients. The sensitivity to change, discriminant capability as well as convergent validity will be also investigated. If the cross-cultural validation of the MVQOLI and QUAL-E questionnaires for advanced cancer patients in a palliative setting have satisfactory psychometric properties, it will allow us to assess the specific dimensions of QoL at the end of life. Current Controlled Trials NCT01545921.

Quasi-experimental designs in practice-based research settings: design and implementation considerations.

PubMed

Handley, Margaret A; Schillinger, Dean; Shiboski, Stephen

2011-01-01

Although randomized controlled trials are often a gold standard for determining intervention effects, in the area of practice-based research (PBR), there are many situations in which individual randomization is not possible. Alternative approaches to evaluating interventions have received increased attention, particularly those that can retain elements of randomization such that they can be considered "controlled" trials. Methodological design elements and practical implementation considerations for two quasi-experimental design approaches that have considerable promise in PBR settings--the stepped-wedge design, and a variant of this design, a wait-list cross-over design, are presented along with a case study from a recent PBR intervention for patients with diabetes. PBR-relevant design features include: creation of a cohort over time that collects control data but allows all participants (clusters or patients) to receive the intervention; staggered introduction of clusters; multiple data collection points; and one-way cross-over into the intervention arm. Practical considerations include: randomization versus stratification, training run in phases; and extended time period for overall study completion. Several design features of practice based research studies can be adapted to local circumstances yet retain elements to improve methodological rigor. Studies that utilize these methods, such as the stepped-wedge design and the wait-list cross-over design, can increase the evidence base for controlled studies conducted within the complex environment of PBR.

Social relationships and cognitive decline: a systematic review and meta-analysis of longitudinal cohort studies.

PubMed

Kuiper, Jisca S; Zuidersma, Marij; Zuidema, Sytse U; Burgerhof, Johannes Gm; Stolk, Ronald P; Oude Voshaar, Richard C; Smidt, Nynke

2016-08-01

Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta-analysis to investigate the relation between poor social relationships and cognitive decline. MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these. We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies. Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Breast Pocket Irrigation with Antibiotic Solution at Implant Insertion: A Systematic Review and Meta-Analysis.

PubMed

Lynch, Jessica M; Sebai, Mohamad E; Rodriguez-Unda, Nelson A; Seal, Stella; Rosson, Gedge D; Manahan, Michele A

2018-06-08

Antibiotic irrigation is routinely used during implant insertion in augmentation mammoplasty procedures. However, the evidence for whether this reduces the incidence of infection or capsular contracture is unclear. Five databases were used to search for all randomized control trials, retrospective cohort and prospective cohort studies containing original data related to the primary outcomes being investigated in this study. The primary outcomes were the effects of antibiotic breast pocket irrigation on clinical infection and capsular contracture. The literature search was designed to combine three concepts: implant or tissue expander-based breast surgery, antibiotic irrigation and clinical infection or capsular contracture. Studies found were screened using specific eligibility criteria. Risk ratios (RR) and 95% confidence interval (CI) were calculated using pooled acquired data from all included studies. The search identified 1256 citations. Three independent screeners identified seven studies that met the inclusion criteria with a pooled population of 4725. This included one prospective and six retrospective studies. A meta-analysis of pooled study data showed significant reductions in clinical infection (RR 0.52, 95% CI 0.33-0.81) and capsular contracture (RR 0.36, 95% CI 0.16-0.83) as a result of antibiotic irrigation. The meta-analyses support the use of antibiotic irrigation of the breast pocket. However, the results of this study are limited by the large proportion of retrospective studies, the small number of studies included, the lack of randomized controlled trials and the heterogeneity of the antibiotic and control regimes used. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CONSTANCES: a general prospective population-based cohort for occupational and environmental epidemiology: cohort profile.

PubMed

Goldberg, Marcel; Carton, Matthieu; Descatha, Alexis; Leclerc, Annette; Roquelaure, Yves; Santin, Gaëlle; Zins, Marie

2017-01-01

WHY THE COHORT WAS SET UP?: CONSTANCES is a general-purpose cohort with a focus on occupational and environmental factors. CONSTANCES was designed as a randomly selected sample of French adults aged 18-69 years at inception; 200 000 participants will be included. At enrolment, the participants are invited to complete questionnaires and to attend a health screening centre (HSC) for a health examination. A biobank will be set up. The follow-up includes an yearly self-administered questionnaire, a periodic visit to an HSC and linkage to social and national health administrative databases. Data collected for participants include social and demographic characteristics, socioeconomic status, life events and behaviours. Regarding occupational and environmental factors, a wealth of data on organisational, chemical, biological, biomechanical and psychosocial lifelong exposure, as well as residential characteristics, are collected at enrolment and during follow-up. The health data cover a wide spectrum: self-reported health scales, reported prevalent and incident diseases, long-term chronic diseases and hospitalisations, sick-leaves, handicaps, limitations, disabilities and injuries, healthcare usage and services provided, and causes of death. To take into account non-participation and attrition, a random cohort of non-participants was set up and will be followed through the same national databases as participants. Inclusions begun at the end of 2012 and more than 110 000 participants were already included by September 2016. Several projects on occupational and environmental risks already applied to a public call for nested research projects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Caffeinated and decaffeinated coffee consumption and melanoma risk: a dose-response meta-analysis of prospective cohort studies.

PubMed

Micek, Agnieszka; Godos, Justyna; Lafranconi, Alessandra; Marranzano, Marina; Pajak, Andrzej

2018-06-01

To determine the association between total, caffeinated and decaffeinated coffee consumption and melanoma risk a dose-response meta-analysis on prospective cohort studies were performed. Eligible studies were identified searching PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by random-effects meta-analysis and the shape of the exposure-outcome curve was modelled linearly and using restricted cubic splines. A total of seven studies eligible for meta-analysis were identified that comprised 1,418,779 participants and 9211 melanoma cases. A linear dose-response meta-analysis showed a significant association between total coffee consumption and melanoma risk. An increase in coffee consumption of one cup per day was associated with a 3% reduction in melanoma risk (RR 0.97; 95% CI 0.95-0.99). Our findings suggest that coffee intake may be inversely associated with incidence of melanoma. Nevertheless, further studies exploring also the role of confounding factors are needed to explain the heterogeneity among studies.

Polymorphism in the promoter region of the Toll-like receptor 9 gene and cervical human papillomavirus infection.

PubMed

Oliveira, Lucas Boeno; Louvanto, Karolina; Ramanakumar, Agnihotram V; Franco, Eduardo L; Villa, Luisa L

2013-08-01

Polymorphism in the Toll-like receptor (TLR) 9 gene has been shown to have a significant role in some diseases; however, little is known about its possible role in the natural history of human papillomavirus (HPV) infections. We investigated the association between a single-nucleotide polymorphism (SNP) (rs5743836) in the promoter region of TLR9 (T1237C) and type-specific HPV infections. Specimens were derived from a cohort of 2462 women enrolled in the Ludwig-McGill Cohort Study. We randomly selected 500 women who had a cervical HPV infection detected at least once during the study as cases. We defined two control groups: (i) a random sample of 300 women who always tested HPV negative, and (ii) a sample of 234 women who were always HPV negative but had a minimum of ten visits during the study. TLR9 genotyping was performed using bidirectional PCR amplification of specific alleles. Irrespective of group, the WT homozygous TLR9 genotype (TT) was the most common form, followed by the heterozygous (TC) and the mutant homozygous (CC) forms. There were no consistent associations between polymorphism and infection risk, either overall or by type or species. Likewise, there were no consistently significant associations between polymorphism and HPV clearance or persistence. We concluded that this polymorphism in the promoter region of TLR9 gene does not seem to have a mediating role in the natural history of the HPV infection.

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

PubMed Central

2011-01-01

Background Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Methods Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Results Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. Conclusions A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health. PMID:21529374

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality.

PubMed

Fenton, Tanis R; Tough, Suzanne C; Lyon, Andrew W; Eliasziw, Misha; Hanley, David A

2011-04-30

Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.

In utero exposure to 25-hydroxyvitamin D and risk of childhood asthma, wheeze, and respiratory tract infections: A meta-analysis of birth cohort studies.

PubMed

Feng, Haixia; Xun, Pengcheng; Pike, Katharine; Wills, Andrew K; Chawes, Bo L; Bisgaard, Hans; Cai, Wei; Wan, Yanping; He, Ka

2017-05-01

Studies of the associations between in utero 25-hydroxyvitamin D (25[OH]D) exposure and risk of childhood asthma, wheeze, and respiratory tract infections are inconsistent and inconclusive. We sought to assess associations between 25(OH)D levels in cord blood or maternal venous blood and risk of offspring's asthma, wheeze, and respiratory tract infections. Data were derived from PubMed, Embase, Google Scholar, references from relevant articles, and de novo results from published studies until December 2015. A random-effects meta-analysis was conducted among 16 birth cohort studies. Comparing the highest with the lowest category of 25(OH)D levels, the pooled odds ratios were 0.84 (95% CI, 0.70-1.01; P = .064) for asthma, 0.77 (95% CI, 0.58-1.03; P = .083) for wheeze, and 0.85 (95% CI, 0.66-1.09; P = .187) for respiratory tract infections. The observed inverse association for wheeze was more pronounced and became statistically significant in the studies that measured 25(OH)D levels in cord blood (0.43; 95% CI, 0.29-0.62; P < .001). Accumulated evidence generated from this meta-analysis suggests that increased in utero exposure to 25(OH)D is inversely associated with the risk of asthma and wheeze during childhood. These findings are in keeping with the results of 2 recently published randomized clinical trials of vitamin D supplementation during pregnancy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

TRAINING ERRORS AND RUNNING RELATED INJURIES: A SYSTEMATIC REVIEW

PubMed Central

Buist, Ida; Sørensen, Henrik; Lind, Martin; Rasmussen, Sten

2012-01-01

Purpose: The purpose of this systematic review was to examine the link between training characteristics (volume, duration, frequency, and intensity) and running related injuries. Methods: A systematic search was performed in PubMed, Web of Science, Embase, and SportDiscus. Studies were included if they examined novice, recreational, or elite runners between the ages of 18 and 65. Exposure variables were training characteristics defined as volume, distance or mileage, time or duration, frequency, intensity, speed or pace, or similar terms. The outcome of interest was Running Related Injuries (RRI) in general or specific RRI in the lower extremity or lower back. Methodological quality was evaluated using quality assessment tools of 11 to 16 items. Results: After examining 4561 titles and abstracts, 63 articles were identified as potentially relevant. Finally, nine retrospective cohort studies, 13 prospective cohort studies, six case-control studies, and three randomized controlled trials were included. The mean quality score was 44.1%. Conflicting results were reported on the relationships between volume, duration, intensity, and frequency and RRI. Conclusion: It was not possible to identify which training errors were related to running related injuries. Still, well supported data on which training errors relate to or cause running related injuries is highly important for determining proper prevention strategies. If methodological limitations in measuring training variables can be resolved, more work can be conducted to define training and the interactions between different training variables, create several hypotheses, test the hypotheses in a large scale prospective study, and explore cause and effect relationships in randomized controlled trials. Level of evidence: 2a PMID:22389869

Maternal and offspring fasting glucose and type 2 diabetes-associated genetic variants and cognitive function at age 8: a Mendelian randomization study in the Avon Longitudinal Study of Parents and Children

PubMed Central

2012-01-01

Background In observational epidemiological studies type 2 diabetes (T2D) and both low and high plasma concentrations of fasting glucose have been found to be associated with lower cognitive performance. These associations could be explained by confounding. Methods In this study we looked at the association between genetic variants, known to be robustly associated with fasting glucose and T2D risk, in the mother and her offspring to determine whether there is likely to be a causal link between early life exposure to glucose and child’s intelligence quotient (IQ) scores in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. We generated a fasting glucose (FGGRS) and a T2D (T2DGRS) genetic risk score and used them in a Mendelian randomization approach. Results We found a strong correlation between the FGGRS and fasting glucose plasma measurements that were available for a subset of children, but no association of either the maternal or the offspring FGGRS with child’s IQ was observed. In contrast, the maternal T2DGRS was positively associated with offspring IQ. Conclusions Maternal and offspring genetic variants which are associated with glucose levels are not associated with offspring IQ, suggesting that there is unlikely to be a causal link between glucose exposure in utero and IQ in childhood. Further exploration in even larger cohorts is required to exclude the possibility that our null findings were due to a lack of statistical power. PMID:23013243

Associations between Yogurt Consumption and Weight Gain and Risk of Obesity and Metabolic Syndrome: A Systematic Review1234

PubMed Central

Martínez-González, Miguel A; Bes-Rastrollo, Maira

2017-01-01

The role of yogurt consumption in the risk of developing overweight, obesity, or metabolic syndrome has been the subject of epidemiologic studies over the last 10 y. A comprehensive literature search on MEDLINE and ISI Web of Knowledge from 1966 through June 2016 was conducted to examine the relation between yogurt consumption and weight gain, as well as the risk of overweight, obesity, or metabolic syndrome, in prospective cohort studies. Ten articles met all the inclusion criteria and were included in our systematic review. Of the 10 cohort studies, 3 analyzed the relation between yogurt consumption and the risk of overweight or obesity, 8 analyzed changes in waist circumference or weight changes, 3 studied the association with the risk of developing metabolic syndrome, and 1 studied the probability of abdominal obesity reversion. Although an inverse association between yogurt consumption and the risk of developing overweight or obesity was not fully consistent or always statistically significant, all studies but one showed in their point estimates inverse associations between yogurt consumption and changes in waist circumference, changes in weight, risk of overweight or obesity, and risk of metabolic syndrome during follow-up, although not all estimates were statistically significant (2 studies). Prospective cohort studies consistently suggested that yogurt consumption may contribute to a reduction in adiposity indexes and the risk of metabolic syndrome. Therefore, there is a need for more prospective studies and high-quality randomized clinical trials to confirm this apparent inverse association. PMID:28096138

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

PubMed

Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

2015-01-01

Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib plus letrozole and 81 to letrozole alone. At the time of the final analysis for progression-free survival (median follow-up 29.6 months [95% CI 27.9-36.0] for the palbociclib plus letrozole group and 27.9 months [25.5-31.1] for the letrozole group), 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group. Median progression-free survival was 10.2 months (95% CI 5.7-12.6) for the letrozole group and 20.2 months (13.8-27.5) for the palbociclib plus letrozole group (HR 0.488, 95% CI 0.319-0.748; one-sided p=0.0004). In cohort 1 (n=66), median progression-free survival was 5.7 months (2.6-10.5) for the letrozole group and 26.1 months (11.2-not estimable) for the palbociclib plus letrozole group (HR 0.299, 0.156-0.572; one-sided p<0.0001); in cohort 2 (n=99), median progression-free survival was 11.1 months (7.1-16.4) for the letrozole group and 18.1 months (13.1-27.5) for the palbociclib plus letrozole group (HR 0.508, 0.303-0.853; one-sided p=0.0046). Grade 3-4 neutropenia was reported in 45 (54%) of 83 patients in the palbociclib plus letrozole group versus one (1%) of 77 patients in the letrozole group, leucopenia in 16 (19%) versus none, and fatigue in four (4%) versus one (1%). Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism (three [4%] patients), back pain (two [2%]), and diarrhoea (two [2%]). No cases of febrile neutropenia or neutropenia-related infections were reported during the study. 11 (13%) patients in the palbociclib plus letrozole group and two (2%) in the letrozole group discontinued the study because of adverse events. The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway. Pfizer. Copyright © 2015 Elsevier Ltd. All rights reserved.