Nursing Question

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Locate a peer-reviewed article that utilizes a meta-analysis design and examines a population health topic that interests you. Your article must be a meta-analysis specifically, not just a systematic review. In 2–3 pages, not including title page and references, address the following: Identify your selected article. Explain what characteristics make this a meta-analysis.Were the inclusion and exclusion criteria clearly stated? How were the articles that were included selected? Do you agree with the researchers’ approach? Explain why or why not.Do you agree with the conclusions? Explain why or why not.Explain how you could apply implications from the study to your nursing practiceReference attached, you can include additional references that are within the last 5 years.

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278
Suicide and Life-Threatening Behavior 49 (1) February 2019
© 2017 The American Association of Suicidology
DOI: 10.1111/sltb.12422
Metaanalysis of Mood and Substance Use
Disorders in Proximal Risk for Suicide Deaths
KENNETH R. CONNER, PSYD, MPH, JEFFREY A. BRIDGE, PHD, DUSTIN J. DAVIDSON,
BA, BS, CARLY PILCHER, BS, AND DAVID A. BRENT, MD
Evidence for proximal risk factors for suicide is based on case–control psychological autopsy studies, with these reports showing that mood and substance
use disorders are the most prevalent mental disorders among suicide decedents
worldwide and are associated with marked risk. However, moderators of risk and
the degree of risk associated with (nonalcohol) drug use disorder are unknown. A
comprehensive search was used to identify 35 case–control psychological autopsy
studies published worldwide over a 30-year period that were metaanalyzed using
random effects models. Major depression, odds ratio (95% confidence interval) = 9.14 (5.53, 15.09), and drug use disorder, OR (95% CI) = 7.18 (3.22,
16.01), had large effect sizes, among other results. Risk estimates associated with
major depression were greater in studies with a larger proportion of women and
those conducted in Asia compared with other regions. There was no evidence of
publication bias or that any one study had a disproportionate impact on findings.
Risk for suicide associated with major depression appears to be moderated by sex
and/or world region. Drug use disorder is a potent risk factor, illustrating the
importance of assessing drug use in clinical risk assessment.
Worldwide, there are more than 800,000
suicide deaths annually, accounting for 50%
of all violent deaths in men and 71% in
women (World Health Organization, 2014).
Although cohort studies have generated
much of the evidence for distal risk factors
for suicide (Franklin et al., 2017), data on
proximal risk factors (i.e., present near time of
death) is based primarily on case–control psychological autopsy studies. With this design,
researchers interview proxy respondents of
suicide decedents, most often family members, and gather comparable information on
nonsuicide control subjects along with additional information obtained from records
when available (e.g., medical records) for the
purpose of making systematic comparisons
between study groups (Conner et al., 2011,
2012).
Psychological autopsy research shows
that mood disorders are the most common
category of mental disorders among suicide
KENNETH R. CONNER, University of Rochester Medical Center, Rochester, NY, USA; JEFFREY
A. BRIDGE, Nationwide Children’s Hospital,
Columbus, OH and Ohio State University,
Columbus, OH, USA; DUSTIN J. DAVIDSON and
CARLY PILCHER, Nationwide Children’s Hospital,
Columbus, OH, USA; DAVID A. BRENT, University
of Pittsburgh, Pittsburgh, PA, USA.
This work was supported by a grant from
the American Foundation for Suicide Prevention
(Conner PI). An earlier version was presented in
June, 2015, at the World Congress of the International Association of Suicide Prevention, Montreal, Canada.
Address correspondence to Kenneth R.
Conner, Department of Emergency Medicine,
University of Rochester Medical Center, Box
655C, Rochester, NY 14642; E-mail: kenneth_
[email protected]
CONNER ET AL.
decedents worldwide (Cavanagh, Carson,
Sharpe, & Lawrie, 2003). Illustrating their
central importance in suicide, a metaanalysis concluded that 26.3% of suicides in
males and 31.6% in females are “attributable” to a mood disorder, highest
among mental disorders, based on a formula that considers both the high prevalence of mood disorders among suicide
decedents and the substantially higher likelihood of a mood disorder in suicide cases
compared to nonsuicide controls (Li, Page,
Martin, & Taylor, 2011). Alcohol or other
drug use disorders are the second most
common category of mental disorder
among suicide decedents (Cavanagh et al.,
2003). Prior metaanalyses of case–control
psychological autopsy studies have generated pooled estimates of risk for suicide
associated with mood disorders and alcohol
or drug use disorders (Arsenault-Lapierre,
Kim, & Turecki, 2004; Cavanagh et al.,
2003; Yoshimasu, Kiyohara, & Miyashita,
2008), but numerous studies with large
sample sizes from different regions of the
world have been conducted since these
reports were published. A more recent
metaanalysis by Cho, Na, Cho, Im, and
Kang (2016) served to update the literature,
but the inclusion criteria required an estimate of risk for any mental disorder, serving to exclude more targeted papers, with
implications for results (see Discussion).
As well, prior metaanalyses did not
determine whether mood disorders and
alcohol or drug use disorders confer differing levels of risk across populations. Along
these lines, it is well-established that there
are age, sex, and regional differences in the
prevalence of mood disorders and alcohol
or drug use disorders among suicide decedents, with females generally more likely to
have mood disorders compared to males,
younger individuals more likely to have
alcohol or drug use disorders compared to
older individuals (Qin, 2011), and suicide
decedents in China showing lower prevalence of depression and alcohol or drug use
disorders compared to Western populations
(Phillips et al., 2002). Furthermore, the
279
metaanalysis by Cho et al. (2016) examined
age, sex, and regional differences in the
presence of any mental disorder (but not
mood or substance use disorder per se)
among suicide cases. Although these reports
are useful, they are limited by the examination of suicide cases only, with the potential
that results merely reflect underlying population distributions of these disorders as
opposed to moderating influences of age
and so forth in suicide risk. Addressing this
topic will require analysis of case–control
data and formal tests of moderating effects,
yet, with rare exception (e.g., Conner,
Beautrais, & Conwell, 2003), formal tests of
moderation that produce statistically significant results in the case–control psychological autopsy research literature are rare, a
limitation that can be overcome by combining the results of studies through metaanalysis. A metaanalysis by Li et al. (2011)
examined risk for suicide associated with
mood disorders and alcohol or drug use
disorders using controlled reports that
included a focus on moderating effects of
sex, age, and region. However, the authors
narrowed their search to studies that
reported risk estimates for various diagnoses
and one or more socio-economic variables
(e.g., low occupational status), resulting in a
restricted number of studies analyzed, with
unclear generalizability to the broader case–
control psychological autopsy literature.
A recent metaanalysis examined risk
for suicide associated with alcohol use disorder, providing a pooled estimate, OR
(95% CI) = 2.59 (1.95, 3.23) (Darvishi, Farhadi, Haghtalab, & Poorolajal, 2015). The
authors also examined age and sex as moderators of the association between alcohol
use disorder and suicide and did not find
evidence of moderation. However, the
analyses combined the results from studies
using different study designs, including
cohort studies that may assess mental disorders years prior to suicide, making the
relevance of the findings to proximal risk
for suicide unclear. The metaanalysis by
Cho et al. (2016) narrowed the focus to
psychological autopsy research studies and
280
MOOD AND SUBSTANCE USE DISORDERS IN SUICIDE
reported risk estimates for any substance
use disorder (i.e., alcohol or drug) and alcohol use disorder broadly defined. However,
neither metaanalysis disentangled subcategories of alcohol use disorder, including
alcohol abuse and alcohol dependence, or
examined nonalcohol drug use disorders.
These are critical gaps because case–control
psychological autopsy research has been
dominated by reports of alcohol use disorder alone or summary substance use disorders variables that combine alcohol and
other drug use disorders, making the contribution of (nonalcohol) drug use disorders
to risk unclear. Disentangling categories of
alcohol use disorder is also needed because
some reports suggest that alcohol dependence but not alcohol abuse is greater in
suicide decedents compared to nonsuicide
controls (Cheng, 1995; Foster, Gillespie,
McClelland, & Patterson, 1999; Kolves,
Varnik, Tooding, & Wasserman, 2006),
which may be attributable to greater alcohol-related severity associated with alcohol
dependence.
We conducted a metaanalysis of
case–control psychological autopsy studies
of suicide to provide updated estimates of
risk associated with mood disorders and
alcohol or drug use disorders; test the moderating effects of age, sex, and region on
these variables; disentangle risk in diagnostic subcategories based on the idea that risk
may vary as a function of illness severity;
and generate novel proximal risk estimates
for nonalcohol drug use disorders.
sufficient to calculate an effect size with
respect to these disorders; (3) in-person
research interviews using a diagnostic instrument with proxy respondents of suicide decedents and with nonsuicide controls and/or
proxy respondents of controls; and (4) examinations of all suicides in a given population
and/or subgroups defined by age, sex, and/or
geographic location but no other criteria
(e.g., a study comparing a general population
sample of suicides and controls ages 60 and
over would be eligible). Exclusion criteria
were as follows: (1) non-English reports; (2)
nonsuicide studies (e.g., examinations of nonlethal suicide attempt); (3) subpopulations of
cases defined other than by age, sex, or geographic location (e.g., hospital patients, prisoners); (4) ineligible study design (e.g.,
record linkage study); (5) results were
unavailable to calculate an effect size for a
mood disorder and/or alcohol or drug use
disorder and suicide or such results were
duplicative of other reports of the same sample; (6) papers published before 1985; and (7)
non-peer-reviewed studies (e.g., book chapters).
The identification of reports for the
metaanalysis is described in Figure 1. First,
electronic searches of PubMed using the
terms “case-control” [All Fields] AND “suicide” [All Fields]) OR “psychological
autopsy” [All Fields] were used to identify
reports between January 1, 1985, and May 9,
2016 (n = 1,559). Second, review of the
abstracts and, when necessary, the full
reports of these studies were used to narrow
the list to nonduplicative reports that met all
eligibility criteria (n = 32). Third, the reference lists of the eligible papers, along with
the reference sections of prior metaanalyses
(Arsenault-Lapierre et al., 2004; Cavanagh
et al., 2003; Darvishi et al., 2015; Yoshimasu
et al., 2008) and comprehensive reviews
(Conner et al., 2011, 2012), were used to
identify three additional studies (N = 35).
METHODS
Literature Search
Inclusion criteria were as follows: (1)
case–control study design that included a suicide decedent group and a nonsuicide control
group, living or dead; (2) descriptive data
provided on one or more mood disorder(s)
and/or alcohol or drug use disorders in suicide cases and controls and/or the results of
adjusted or unadjusted comparisons that were
Data Abstraction and Coding
Standardized data collection forms
were developed for abstracting data (Lipsey
CONNER ET AL.
281
PubMED Search
N=1559
misuse). Mood disorders included five categories: (1) mood disorder (broadest); (2)
minor depression or dysthymic disorder; (3)
major depression; (4) depression with psychosis; and (5) bipolar disorder. Alcohol
and drug use disorders included five categories: (1) substance misuse or substance
use disorder (substance use disorder)
(broadest); (2) nonalcohol drug misuse or
drug use disorder (drug use disorder); (3)
alcohol abuse; (4) alcohol dependence; and
(5) alcohol misuse or alcohol use disorder
(alcohol use disorder). Data from separate
reports of the same data set were included
when they provided nonoverlapping results
pertinent to the metaanalysis, including
estimates for different diagnoses (e.g.,
Kolves, Sisask, et al., 2006; Kolves, Varnik,
et al., 2006) or examinations of different
age groups (e.g., Chan et al., 2009; Chiu
et al., 2004). Methodological quality ratings
were generated by one of the authors
(KRC) using a 14-item rating scale (score
range 0–18) that included 10 applicable
items from a standard measure (Downs &
Black, 1998) and four novel items created
for the current study; for example, “What
was the response rate for cases in the
study?” ≥75% (scored 2), 50–74% (scored
1), ≤49% or unreported (scored 0).
N=947
N=605
N=112
N=32
N=35
Nonsuicide outcome
N=612
Ineligible subpopulation
N=342
Ineligible study design
N=493
Information lacking or duplicative
N=80
Hand search of reference sections
N=3
Figure 1. Selection of studies for metaanalysis.
& Wilson, 2001). The studies were coded
by one of the authors (DJD) who reviewed
the codes regularly with a second author
(JAB) and, when there were questions, they
consulted with a third author (KRC) to
reach a consensus. The codes included: date
of publication; region; country; sample size
(cases, controls); participation rates (when
available); age (mean, range); sex distribution; race/ethnic distribution when available; other demographic characteristics
when available (e.g., education); nature of
control group (e.g., community sample,
injury decedents); instrument used to assess
mental disorders; diagnostic system; and
relevant results including descriptive, unadjusted, and adjusted findings.
Age, sex, and region were defined by
mean age of cases (median age or age range
used if mean age not available); proportion
of male cases; and region of data collection
including Asia, Australia or Oceania, Central America, Europe, and North America.
Diagnoses of mood disorders and substance
use disorders were used if they were based
on one of the versions of the Diagnostic and
Statistical Manual (e.g., American Psychiatric
Association, 1994), International Classification
of Diseases (e.g., World Health Organization, 1995), or if we determined that they
were a reasonable proxy (e.g., substance
Analyses
We obtained pooled estimates of the
size of associations between mood disorders
and alcohol or drug use disorders with
suicide using random effects models
(DerSimonian & Laird, 1986). We chose
random effects models instead of fixed
effects models in anticipation of heterogeneous effect sizes (Cooper, Hedges, &
Valentine, 2009). Statistical analyses were
performed using Comprehensive Metaanalyses version 2.2 (Biostat, Englewood, NJ)
and SPSS version 24 (SPSS Inc, Chicago,
IL). Odds ratios and 95% confidence intervals (OR, 95% CI) generated in these
models provided measures of effect size. As
data allowed, we examined world region,
sex, age, and methodological quality as
282
MOOD AND SUBSTANCE USE DISORDERS IN SUICIDE
moderators of risk associated with mood
disorders, major depression, minor depression or dysthymia, substance use disorder,
and alcohol use disorder; there were too
few reports to examine moderating influences on other disorders. World region and
age were categorical moderators of outcome. For continuous moderators, mixed
effects metaregression was used to explore
whether proportion of male cases and
methodological quality influenced outcome.
Continuous moderators that showed an
association with outcome were dichotomized by median split and reexamined as
categorical moderators. Heterogeneity of
effect sizes was examined using the Cochran
Q chi-square statistic (p ≤ .10) and the I2
statistic, a transformation of Q that indicates the percentage of variation in the
effect size estimate attributable to heterogeneity rather than sampling error (Higgins
& Thompson, 2002). Publication bias was
assessed visually using funnel plots and
quantitatively using an adjusted rank correlation test (Begg & Mazumdar, 1994) and a
regression procedure to measure funnel plot
asymmetry (Egger, Davey Smith, Schneider,
& Minder, 1997). We performed leave-oneout analyses by iteratively deleting each
study and calculating the resulting effect to
determine whether any study unduly influenced pooled effect size estimates.
results for the disorders examined in this
review.
RESULTS
Eligible Studies
Characteristics of the 35 studies
analyzed are listed in Table 1. Region of
studies include Asia (n = 11), Australia or
Oceania (n = 5), Central America (n = 1),
Europe (n = 12), and North America (6).
Age categories include adolescent and/or
young adult (n = 10), mixed age (n = 19),
and older adult (n = 6). Across all studies,
the average proportion of male cases was
0.71 (standard deviation [SD] = 0.14). Quality ratings ranged from 4 to 17, with mean
(SD) = 12.7 (3.4). The studies reported the
Main Effects
The primary results of the analyses
are shown in Table 2. Mood disorder
broadly defined and major depression
showed the largest effect sizes in risk for
suicide: mood disorder, OR (95%
CI) = 14.34 (9.10, 22.57); major depression,
OR (95% CI) = 9.14 (5.53, 15.09). The
effect sizes for bipolar disorder, depression
with psychosis, and minor depression or
dysthymic disorder were statistically significant although smaller in magnitude, in the
range of three- to fourfold risk. The results
of the analyses of the various alcohol and
drug use disorders are also shown in
Table 2, with each disorder showing statistically significant results in the range of
threefold risk for suicide and higher, with
the highest risk estimate for drug use disorder, OR (95% CI) = 7.18 (3.22, 16.01). Significant heterogeneity across studies was
noted for each disorder (I2 range, 39%–
80%), with the exception of depression with
psychosis and bipolar disorder.
Moderator Analyses
There is evidence of a moderating
effect of region on risk for suicide associated
with mood disorder (Q3 = 9.60, p = .022)
and major depression (Q2 = 7.63, p = .022),
with studies conducted in Asia showing the
highest pooled risk estimate for each of these
disorders. However, the test for a moderating effect of region on risk for suicide associated with substance use disorder was
nonsignificant (Q3 = 4.98, p = .173). Also,
risk for suicide associated with major depression was higher in studies with larger proportions of females (b = 4.48, Q1 = 6.87,
p = .009). Dichotomizing proportion of
male cases by median split (≤ 0.70 vs. > .70)
revealed significantly larger effect sizes
(Q1 = 3.97, p = .046) in studies where the
proportion of male cases was ≤ .70
(OR = 15.34,
95%
CI = 7.17–32.83)
202 Australia/
Oceania
140 North
America
67 North
America
150 Asia
150 Asia
117 Asia
3. Beautrais (2001)
16. Freuchen, Kjelsberg, Lundervold, and
Groholt (2012)
13. De Leo, Draper, Snowdon, and K~
olves
(2013a)
14. De Leo, Draper, Snowdon, and K~
olves
(2013b)
15. Foster et al. (1999)
41 Europe
193 Australia/
Oceania
86 North
America
84 Australia/
Oceania
261 Australia/
Oceania
117 Europe
11. Conner et al. (2003)
12. Conwell et al. (2010)
117 Asia
70 Asia
9. Cheng, Chen, Chen, and Jenkins (2000)
10. Chiu et al. (2004)
6. Chan et al. (2009)
7. Chen et al. (2006)
8. Cheng (1995)
4. Brent, Baugher, Bridge, Chen, and Chiappetta
(1999)
5. Brent et al. (1993)
194 Europe
84 Europe
1. Almasi et al. (2009)
2. Appleby, Cooper, Amos, and Faragher (1999)
Region
N
Report
Description of Reports Analyzed
TABLE 1
71
12
14
NR
Adolescent/
young adult
14
75
Mixed, Older
adult
Mixed
13
15
85
73
Older adult
16
14
8
Mixed
77
62
46
9
9
13
13
85
64
64
62
16
16
16
8
85
78
81
81
% Male Quality
(cases)
rating
Mixed
Mixed
Older adult
Adolescent/
young adult
Adolescent/
young adult
Mixed
Mixed
Mixed
Mixed
Adolescent/
young adult
Mixed
Age category
(continued)
Mood disorder, major depression, SUD,
alcohol abuse, alcohol dependence, AUD
Mood disorder, minor depression
Major depression, bipolar disorder, AUD
Mood disorder, major depression, SUD,
AUD
Mood disorder, SUD
Major depression
Mood disorder
Minor depression, alcohol abuse, alcohol
dependence
Major depression, SUD
Mood disorder, minor depression, major
depression, alcohol dependence
Drug use disorder, alcohol dependence
Major depression, drug use disorder, AUD
Mood disorder, SUD
Mood disorder, SUD
Mood disorder, minor depression, SUD
SUD
Diagnoses examined
CONNER ET AL.
283
Adolescent/
young adult
Mixed
84 Australia/
Oceania
108 Central
America
95 Europe
55 North
America
163 Europe
23. Page et al. (2014)
29. Shafii, SteltzLenarsky, Derrick, and Beckner
(1988)
30. Tong and Phillips (2010)
31. Vijayakumar et al. (1999)
28. Shaffer et al. (1996)
25. Preville, Hebert, Boyer, Bravo, and Seguin
(2005)
26. Renaud, Berlim, McGirr, Tousignant, and
Turecki (2008)
27. Schneider et al. (2006)
120 North
America
21 North
America
895 Asia
100 Asia
Older adult
427 Europe
419 Europe
100 Asia
20. Kolves, Varnik, et al. (2006)
21. Kolves, Sisask, et al. (2006)
22. Manoranjitham et al. (2010)
24. Palacio et al. (2007)
Mixed
115 Asia
Adolescent/
young adult
Adolescent/
young adult
Mixed
Mixed
Adolescent/
young adult
Mixed
Mixed
Mixed
Mixed
Older adult
Mixed
54 Europe
100 Asia
Age category
17. Harwood, Hawton, Hope, and Jacoby (2001)
18. Khan, Mahmud, Karim, Zaman, and Prince
(2008)
19. Kim et al. (2003)
Region
N
Report
(continued)
TABLE 1
16
8
17
17
91
51
55
13
64
79
8
13
12
12
15
15
14
11
6
14
78
75
81
85
80
80
59
100
41
83
% Male Quality
(cases)
rating
(continued)
Major depression, alcohol abuse, alcohol
dependence
Mood disorder, minor depression, bipolar
disorder, SUD, drug use disorder, AUD
Mood disorder, minor depression, major
depression, bipolar disorder, SUD, AUD
Mood disorder, major depression, bipolar
disorder, SUD, drug use disorder, AUD
Mood disorder, minor depression, major
depression, SUD
Mood disorder, SUD
Minor depression, major depression,
bipolar disorder, drug use disorder, AUD
Minor depression, major depression, SUD
Major depression, bipolar disorder, drug
use disorder, alcohol abuse, alcohol
dependence
Alcohol abuse, alcohol dependence
SUD
Minor depression, major depression,
alcohol dependence
Mood disorder, major depression, SUD
Mood disorder, SUD
SUD
Diagnoses examined
284
MOOD AND SUBSTANCE USE DISORDERS IN SUICIDE
compared to studies with > .70 proportion
of male cases (OR = 5.37, 95% CI = 2.67–
10.80). Studies with higher quality ratings
generated higher risk estimates associated
with alcohol use disorder (p = .003) and
drug use disorder (p < .001). There was a lack of evidence of moderating effects of region or gender on risk associated with other disorders, and we found no evidence of moderating effects of age. 4 Publication Bias and Leave-One-Out Analysis 100 Europe 35. Zonda (2006) AUD, alcohol use disorder; SUD, substance use disorder; NR, not reported. 67 392 Asia 34. Zhang, Xiao, and Zhou (2010) Mixed 11 55 Mood disorder, minor depression, major depression, bipolar disorder, SUD, drug use disorder, AUD Major depression, drug use disorder, AUD 16 56 Adolescent/ young adult Adolescent/ young adult 88 Europe 33. Waern (2003) Older adult 85 Europe 54 16 Mood disorder, minor depression, major depression, bipolar disorder, SUD AUD 285 32. Waern et al. (2002) Report (continued) TABLE 1 N Region Age category % Male Quality (cases) rating Diagnoses examined CONNER ET AL. Separate analyses of publication bias were conducted for each pooled estimate of risk of suicide associated with mood disorders and alcohol or drug use disorders. We did not find evidence of publication bias in any of the models based on visual inspection of the funnel plots, the adjusted rank correlation tests, and the regression intercept approach (data available on request). Sensitivity analyses did not suggest that any individual study unduly influenced the pooled risk estimates reported in Table 2 (data available on request). DISCUSSION Mood Disorders The current metaanalysis of case–control psychological autopsy studies conducted worldwide over a 30-year period provided estimates of proximal risk for suicide associated with various mood and substance use disorders and tested moderators of risk. The risk estimate for major depression was significantly lower than that provided by Cho et al. (2016) which may be presumed to be attributable to the differing search strategies, with the current search uncovering a greater number of relevant reports (n = 19 vs. n = 12). Nonetheless, the risk estimate that we obtained for major depression is on the order of ninefold risk, underscoring that it is a potent risk factor. In contrast, the estimate of proximal risk for suicide associated with 286 MOOD AND SUBSTANCE USE DISORDERS IN SUICIDE TABLE 2 Risk for Suicide Associated with Mood and Alcohol and Drug Use Disorders Heterogeneity Disorder Mood disorder Minor depression Major depression Depression with psychosis Bipolar disorder Substance use disorder Drug use disorder Alcohol abuse Alcohol dependence Alcohol use disorder N of studies OR 95% CI lower 95% CI upper p Value Qdf Within p Value Variance explained, % 18 12 19 3 14.34 2.73 9.14 3.37 9.10 1.53 5.53 1.01 22.57 4.85 15.09 11.24 Purchase answer to see full attachment