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On February 23, 2018, PubMed Central Canada (PMC Canada) will be taken offline permanently. No author manuscripts will be deleted, and the approximately 2,900 manuscripts authored by Canadian Institutes of Health Research (CIHR)-funded researchers currently in the archive will be copied to the National Research Council’s (NRC) Digital Repository over the coming months. These manuscripts along with all other content will also remain publicly searchable on PubMed Central (US) and Europe PubMed Central, meaning such manuscripts will continue to be compliant with the Tri-Agency Open Access Policy on Publications.

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1.  On the implication of structural zeros as independent variables in regression analysis: applications to alcohol research 
Journal of data science : JDS  2014;12(3):439-460.
In alcohol studies, drinking outcomes such as number of days of any alcohol drinking (DAD) over a period of time do not precisely capture the differences among subjects in a study population of interest. For example, the value of 0 on DAD could mean that the subject was continually abstinent from drinking such as lifetime abstainers or the subject was alcoholic, but happened not to use any alcohol during the period of interest. In statistics, zeros of the first kind are called structural zeros, to distinguish them from the sampling zeros of the second type. As the example indicates, the structural and sampling zeros represent two groups of subjects with quite different psychosocial outcomes. In the literature on alcohol use, although many recent studies have begun to explicitly account for the differences between the two types of zeros in modeling drinking variables as a response, none has acknowledged the implications of the different types of zeros when such modeling drinking variables are used as a predictor. This paper serves as the first attempt to tackle the latter issue and illustrate the importance of disentangling the structural and sampling zeros by using simulated as well as real study data.
PMCID: PMC5628625
number of days of drinking alcohol; NHANES; structural zero; zero-inflated count data; zero-inflated models for count data
2.  The Differences and Similarities Between Two-Sample T-Test and Paired T-Test 
Shanghai Archives of Psychiatry  null;29(3):184-188.
In clinical research, comparisons of the results from experimental and control groups are often encountered. The two-sample t-test (also called independent samples t-test) and the paired t-test are probably the most widely used tests in statistics for the comparison of mean values between two samples. However, confusion exists with regard to the use of the two test methods, resulting in their inappropriate use. In this paper, we discuss the differences and similarities between these two t-tests. Three examples are used to illustrate the calculation procedures of the two-sample t-test and paired t-test.
PMCID: PMC5579465  PMID: 28904516
independent t-test; paired t-test; pre- and post-treatment; matched paired data
3.  Correlation and agreement: overview and clarification of competing concepts and measures 
Shanghai Archives of Psychiatry  null;28(2):115-120.
Summary: Agreement and correlation are widely-used concepts that assess the association between variables. Although similar and related, they represent completely different notions of association. Assessing agreement between variables assumes that the variables measure the same construct, while correlation of variables can be assessed for variables that measure completely different constructs. This conceptual difference requires the use of different statistical methods, and when assessing agreement or correlation, the statistical method may vary depending on the distribution of the data and the interest of the investigator. For example, the Pearson correlation, a popular measure of correlation between continuous variables, is only informative when applied to variables that have linear relationships; it may be non-informative or even misleading when applied to variables that are not linearly related. Likewise, the intraclass correlation, a popular measure of agreement between continuous variables, may not provide sufficient information for investigators if the nature of poor agreement is of interest. This report reviews the concepts of agreement and correlation and discusses differences in the application of several commonly used measures.
PMCID: PMC5004097  PMID: 27605869
concordance correlation; intraclass correlation; Kendall's tau; non-linear association; Pearson's correlation; Spearman's rho
4.  Mood-, Anxiety-, and Substance Use Disorders and Suicide Risk in a Military Population Cohort 
There are meager prospective data from nonclinical samples on the link between anxiety disorders and suicide or the extent to which the association varies over time. We examined these issues in a cohort of 309,861 United States Air Force service members, with 227 suicides over follow-up. Mental disorder diagnoses including anxiety, mood, and substance use disorders (SUD) were based on treatment encounters. Risk for suicide associated with anxiety disorders were lower compared to mood disorders and similar to SUD. Moreover, the associations between mood and anxiety disorders with suicide were greatest within a year of treatment presentation.
PMCID: PMC4863230  PMID: 23094649
suicide; mental disorder; risk factor; military; cohort
5.  Relationships among three popular measures of differential risks: relative risk, risk difference, and odds ratio 
The relative risk, risk difference, and odds ratio are the three most commonly used measures for comparing the risk of disease between different groups. Although widely popular in biomedical and psychosocial research, the relationship among the three measures has not been clarified in the literature. Many researchers incorrectly assume a monotonic relationship, such that higher (or lower) values in one measure are associated with higher (or lower) values in the other measures. In this paper we discuss three theorems and provide examples demonstrating that this is not the case; there is no logical relationship between any of these measures. Researchers must be very cautious when implying a relationship between the different measures or when combining results of studies that use different measures of risk.
PMCID: PMC4984606  PMID: 27688647
odds ratio; relative risk; risk difference
6.  Adapting Interpersonal Psychotherapy for Older Adults at Risk for Suicide 
To pilot a psychological intervention adapted for older adults at-risk for suicide.
A focused, uncontrolled, pre-to-post-treatment psychotherapy trial. All eligible participants were offered the study intervention.
Outpatient mental healthcare provided in the psychiatry department of an academic medical center in a mid-sized Canadian city.
Seventeen English-speaking adults 60 years or older, at- risk for suicide by virtue of current suicide ideation, death ideation, and/or recent self-injury.
A 16-session course of Interpersonal Psychotherapy (IPT) adapted for older adults at-risk for suicide who were receiving medication and/or other standard psychiatric treatment for underlying mood disorders.
Participants completed a demographics form, screens for cognitive impairment and alcohol misuse, a semi-structured diagnostic interview, and measures of primary (suicide ideation and death ideation), and secondary study outcomes (depressive symptom severity; social adjustment and support; psychological well-being), and psychotherapy process measures.
Participants experienced significant reductions in suicide ideation, death ideation, and depressive symptom severity, and significant improvement in perceived meaning in life, social adjustment, perceived social support, and other psychological well-being variables.
Study participants experienced enhanced psychological well-being and reduced symptoms of depression and suicide ideation over the course of IPT adapted for older adults at-risk for suicide. Larger, controlled trials are needed to further evaluate the impact of this novel intervention and to test methods for translating and integrating focused interventions into standard clinical care with at-risk older adults.
PMCID: PMC4211998  PMID: 24840611
Suicide; suicide ideation; psychotherapy; treatment; Interpersonal Psychotherapy; IPT; psychological well-being; meaning in life
7.  The Avalanche Hypothesis and Compression of Morbidity: Testing Assumptions through Cohort-Sequential Analysis 
PLoS ONE  2015;10(5):e0123910.
The compression of morbidity model posits a breakpoint in the adult lifespan that separates an initial period of relative health from a subsequent period of ever increasing morbidity. Researchers often assume that such a breakpoint exists; however, this assumption is hitherto untested.
To test the assumption that a breakpoint exists—which we term a morbidity tipping point—separating a period of relative health from a subsequent deterioration in health status. An analogous tipping point for healthcare costs was also investigated.
Four years of adults’ (N = 55,550) morbidity and costs data were retrospectively analyzed. Data were collected in Pittsburgh, PA between 2006 and 2009; analyses were performed in Rochester, NY and Ann Arbor, MI in 2012 and 2013. Cohort-sequential and hockey stick regression models were used to characterize long-term trajectories and tipping points, respectively, for both morbidity and costs.
Morbidity increased exponentially with age (P<.001). A morbidity tipping point was observed at age 45.5 (95% CI, 41.3-49.7). An exponential trajectory was also observed for costs (P<.001), with a costs tipping point occurring at age 39.5 (95% CI, 32.4-46.6). Following their respective tipping points, both morbidity and costs increased substantially (Ps<.001).
Findings support the existence of a morbidity tipping point, confirming an important but untested assumption. This tipping point, however, may occur earlier in the lifespan than is widely assumed. An “avalanche of morbidity” occurred after the morbidity tipping point—an ever increasing rate of morbidity progression. For costs, an analogous tipping point and “avalanche” were observed. The time point at which costs began to increase substantially occurred approximately 6 years before health status began to deteriorate.
PMCID: PMC4427176  PMID: 25962130
8.  Parent and Child Psychopathology and Suicide Attempts among Children of Parents with Alcohol Use Disorder 
Parents with psychopathology such as alcohol use disorder (AUD) that confers risk for suicide attempt (SA) may have children who are more likely to develop such psychopathology and to attempt suicide, suggesting that risk may be “transmitted” from parents to children. We examined this phenomenon during the transition from childhood to adolescence, when risk for SA increases dramatically. A cohort of 418 children were examined at average age 9.4 (range 7–14) years at enrollment (Time 1, childhood) and approximately five years later, prior to reaching age 18 (Time 2, adolescence). One or both biological parents, oversampled for AUD, were also interviewed. Structural equation models (SEM) examined father-child, mother-child, and either/both parent-child associations. The primary outcome was SA over follow-up among offspring, assessed at Time 2. As hypothesized, parental antisocial personality disorder predicted conduct disorder symptoms in offspring both during childhood and adolescence (parent-child model, father-child model) and maternal AUD predicted conduct disorder symptoms during childhood (mother-child model). However, we did not find evidence to support transmission of depression from parents to offspring either during childhood or adolescence, and parent psychopathology did not show statistically significant associations with SA during adolescence. In conclusion, we conducted a rare study of parent-to-child “transmission” of risk for SA that used a prospective research design, included diagnostic interviews with both parents and offspring, and examined the transition from childhood to adolescence, and the first such study in children of parents with AUD. Results provided mixed support for hypothesized parent-child associations.
PMCID: PMC4059391  PMID: 24716789
adolescent; parent; suicide attempt; alcohol use disorder; risk factor
9.  Log-transformation and its implications for data analysis 
Shanghai Archives of Psychiatry  2014;26(2):105-109.
The log-transformation is widely used in biomedical and psychosocial research to deal with skewed data. This paper highlights serious problems in this classic approach for dealing with skewed data. Despite the common belief that the log transformation can decrease the variability of data and make data conform more closely to the normal distribution, this is usually not the case. Moreover, the results of standard statistical tests performed on log-transformed data are often not relevant for the original, non-transformed data.We demonstrate these problems by presenting examples that use simulated data. We conclude that if used at all, data transformations must be applied very cautiously. We recommend that in most circumstances researchers abandon these traditional methods of dealing with skewed data and, instead, use newer analytic methods that are not dependent on the distribution the data, such as generalized estimating equations (GEE).
PMCID: PMC4120293  PMID: 25092958
hypothesis testing; outliners; lon-normal distribution; normal distribution; skewness
10.  Power analysis for cross-sectional and longitudinal study designs 
Shanghai Archives of Psychiatry  2013;25(4):259-262.
PMCID: PMC4054560  PMID: 24991165
11.  On Fitting Generalized Linear Mixed-effects Models for Binary Responses using Different Statistical Packages 
Statistics in medicine  2011;30(20):2562-2572.
The generalized linear mixed-effects model (GLMM) is a popular paradigm to extend models for cross-sectional data to a longitudinal setting. When applied to modeling binary responses, different software packages and even different procedures within a package may give quite different results. In this report, we describe the statistical approaches that underlie these different procedures and discuss their strengths and weaknesses when applied to fit correlated binary responses. We then illustrate these considerations by applying these procedures implemented in some popular software packages to simulated and real study data. Our simulation results indicate a lack of reliability for most of the procedures considered, which carries significant implications for applying such popular software packages in practice.
PMCID: PMC3175267  PMID: 21671252
Integral Approximation; Linearization; GLIMMIX; lme4; NLMIXED; R; SAS; ZELIG
12.  Test of a Clinical Model of Drinking and Suicidal Risk 
There are few data on the role of drinking patterns in suicidal thoughts or behavior among alcohol dependent individuals (ADIs), and meager data on variables that may influence the role of drinking in suicidal thoughts and behavior. This study tested a heuristic model that predicts that drinking promotes suicidal thoughts and behavior, the association is mediated (accounted for) by depressive symptoms, and that anger moderates (increases) the risk associated with intense drinking.
Data from Project MATCH, a multi-site alcohol use disorders treatment trial, were analyzed using structural equation modeling. There were 1,726 participants including 24% women and a mean age of 40.2 ± 11.0 years. Subjects were assessed at baseline and at 3-, 9-, and 15-month follow-up. Two categorical measures (presence/absence) of suicidal ideation (SI) were used that were analyzed in separate models. Predictors of interest were continuous assessments of average drinking intensity (i.e., drinks per drinking day or DDD), drinking frequency (i.e., percent days abstinent or PDA), depression, and anger.
Both DDD and PDA were associated with SI at a statistically significant level, with PDA showing an inverse association. Depression scores served as a partial mediator or a full mediator of the drinking – SI relationship depending on the measure of SI used in the analysis. The models testing anger scores as a moderator fit the data poorly and did not support that anger serves as a moderator of the drinking – SI association.
Greater drinking intensity and drinking frequency predict SI among ADIs and depression serves as a mediator of these associations but anger does not appear to serve as a moderator. Further research is required to clarify if depression serves as a partial- or full mediator and to see if the results herein extend to suicidal behavior (i.e., suicide attempt, suicide).
PMCID: PMC3005075  PMID: 20958331
suicide; alcohol dependence; drinking; depression
13.  Detection of depression in older adults by family and friends: distinguishing mood disorder signals from the noise of personality and everyday life 
The capacity of friends and family member informants to make judgments about the presence of a mood disorder history in an older primary care patient has theoretical, clinical, and public health significance. This study examined the accuracy of informant-reported mood disorder diagnoses in a sample of primary care patients aged 65 years or older. We hypothesized that the accuracy (sensitivity and specificity) of informant reports would vary with the patient's personality.
Hypotheses were tested in 191 dyads consisting of patients and their friends or relatives (informants) recruited from primary care settings. Gold-standard mood disorder diagnoses were established at consensus conferences based on a review of medical charts and data collected in a structured interview with the patient. Patients completed an assessment battery that included the NEO-Five Factor Inventory.
Sensitivity and specificity of informant-derived mood disorder diagnoses were related to patient personality. Sensitivity of informant-derived lifetime mood disorder diagnoses was compromised by higher Extraversion and higher Agreeableness. Specificity of informant-derived lifetime mood disorder diagnoses was compromised by lower Agreeableness and higher Conscientiousness.
Patient personality has implications for the accuracy of mood disorder histories provided by friends and family members. Given that false negatives can have grave consequences, we recommend that practitioners be particularly vigilant when interpreting collateral information about their extraverted, agreeable patients.
PMCID: PMC3032027  PMID: 20880426
personality; depression; informants; primary care
14.  A New Analytic Framework for Moderation Analysis --- Moving Beyond Analytic Interactions 
Journal of data science : JDS  2009;7(3):313-329.
Conceptually, a moderator is a variable that modifies the effect of a predictor on a response. Analytically, a common approach as used in most moderation analyses is to add analytic interactions involving the predictor and moderator in the form of cross-variable products and test the significance of such terms. The narrow scope of such a procedure is inconsistent with the broader conceptual definition of moderation, leading to confusion in interpretation of study findings. In this paper, we develop a new approach to the analytic procedure that is consistent with the concept of moderation. The proposed framework defines moderation as a process that modifies an existing relationship between the predictor and the outcome, rather than simply a test of a predictor by moderator interaction. The approach is illustrated with data from a real study.
PMCID: PMC2790290  PMID: 20161453
Analytic interactions; Mixed-effects model; Non-linear model; Varying-coefficient regression model
15.  Adapting Interpersonal Psychotherapy for Older Adults at Risk for Suicide: Preliminary Findings 
We report preliminary findings of the first ever study testing a 16-week course of Interpersonal Psychotherapy (IPT) modified for older outpatients at elevated risk for suicide. Participants were referred from inpatient and outpatient medicine and mental health services. Psychotherapy sessions took place in a therapist’s office in a teaching hospital. Twelve adults 60 years or older (M=70.5, SD=6.1) with current thoughts of suicide (suicide ideation) or a wish to die (death ideation) or with recent self-injurious behavior were recruited into weekly sessions of IPT; one was subsequently excluded due to severe cognitive impairment. Participants completed measures of suicide ideation, death ideation, and depressive symptom severity at pre-treatment, mid-treatment, post-treatment, and at 3-month follow-up periods, and measures of therapeutic process variables. Preliminary findings of this uncontrolled pre-post-treatment study support the feasibility of recruiting and retaining older adults at-risk for suicide into psychotherapy research and suggest that adapted IPT is tolerable and safe. Findings indicate a substantial reduction in participant suicide ideation, death ideation, and depressive symptoms; controlled trials are needed to further evaluate these findings. We discuss implications for clinical care with at-risk older adults.
PMCID: PMC2889497  PMID: 20574546
Suicide; suicide ideation; suicidal behavior; geriatric; elderly; older adults; psychotherapy; interventions; treatment; IPT; Interpersonal Psychotherapy
16.  Predicting Sexual Risk Behaviors among Adolescent and Young Women Using a Prospective Diary Method 
Research in nursing & health  2008;31(4):329-340.
We describe the sexual risk behaviors, psychological distress, and substance use of 102 late adolescent girls and identify predictors of protected and unprotected vaginal sex. Participants completed questionnaires assessing hypothesized predictors and then daily behavioral diaries for 12 weeks. Protected intercourse was predicted by baseline sexual behavior, greater knowledge, positive condom attitudes, lower perceived condom-use difficulty, greater condom-use intentions, more drinking days, less binge drinking, less Ecstasy use, and lower psychological distress. Unprotected intercourse was predicted by baseline sexual behavior, binge drinking, Ecstasy and opiate use, fewer drinking days, and fewer daily drinks. These findings suggest that psychological distress, substance use, and sexual risk behavior are interconnected and should be considered collectively in interventions for adolescent females.
PMCID: PMC2562714  PMID: 18231976
sexual behavior; HIV; adolescent girls; substance use; depression; diary

Results 1-16 (16)