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      The association between mental illness and all-cause mortality in patients with cirrhosis: a Veterans Affairs retrospective cohort study

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          Background:

          Mental health diagnoses are common and known to impact key outcomes in patients with chronic illnesses including cirrhosis. However, the independent impact of psychiatric comorbidities on mortality in these patients and potential mitigating effects of outpatient mental health–related care has not been well characterized.

          Methods:

          This was a retrospective cohort study of patients with cirrhosis in the Veterans Health Administration between 2008 and 2021. Adjusted Cox regression was performed to evaluate the association between mental health–related diagnoses [groups: alcohol use disorder (AUD)/substance use disorder (SUD) alone, non-AUD/SUD alone, and any mental health diagnosis (AUD/SUD or non-AUD/SUD)] and all-cause mortality. In subgroup analyses, the impact of regular outpatient mental health visits was also assessed.

          Results:

          We identified 115,409 patients, 81.7% of whom had any mental health diagnosis at baseline. During the study window there was a significant increase in the number of mental health clinic visits per person-year (β=0.078, 95% CI: 0.065–0.092, p < 0.001), but a decrease in AUD/SUD clinic utilization ( p < 0.001). In regression models, there was a 54% increased hazard in all-cause mortality for any mental health diagnosis, 11% for non-AUD/SUD, and 44% for AUD/SUD (each p < 0.001). Regular mental health visits resulted in a 21% decreased risk in all-cause mortality for AUD/SUD diagnosis, compared with 3% and 9% for any mental health diagnosis and non-AUD/SUD diagnosis, respectively (each p < 0.001).

          Conclusions:

          Mental illness is associated with an increased risk of all-cause mortality in veterans with cirrhosis. Regular outpatient mental health care may be protective against all-cause mortality, particularly among patients with AUD/SUD. Future studies should focus on relevant clinical practice changes, including implementing integrated care programs.

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          Most cited references46

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          Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples

          The propensity score is a subject's probability of treatment, conditional on observed baseline covariates. Conditional on the true propensity score, treated and untreated subjects have similar distributions of observed baseline covariates. Propensity-score matching is a popular method of using the propensity score in the medical literature. Using this approach, matched sets of treated and untreated subjects with similar values of the propensity score are formed. Inferences about treatment effect made using propensity-score matching are valid only if, in the matched sample, treated and untreated subjects have similar distributions of measured baseline covariates. In this paper we discuss the following methods for assessing whether the propensity score model has been correctly specified: comparing means and prevalences of baseline characteristics using standardized differences; ratios comparing the variance of continuous covariates between treated and untreated subjects; comparison of higher order moments and interactions; five-number summaries; and graphical methods such as quantile–quantile plots, side-by-side boxplots, and non-parametric density plots for comparing the distribution of baseline covariates between treatment groups. We describe methods to determine the sampling distribution of the standardized difference when the true standardized difference is equal to zero, thereby allowing one to determine the range of standardized differences that are plausible with the propensity score model having been correctly specified. We highlight the limitations of some previously used methods for assessing the adequacy of the specification of the propensity-score model. In particular, methods based on comparing the distribution of the estimated propensity score between treated and untreated subjects are uninformative. Copyright © 2009 John Wiley & Sons, Ltd.
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            Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies

            The propensity score is defined as a subject's probability of treatment selection, conditional on observed baseline covariates. Weighting subjects by the inverse probability of treatment received creates a synthetic sample in which treatment assignment is independent of measured baseline covariates. Inverse probability of treatment weighting (IPTW) using the propensity score allows one to obtain unbiased estimates of average treatment effects. However, these estimates are only valid if there are no residual systematic differences in observed baseline characteristics between treated and control subjects in the sample weighted by the estimated inverse probability of treatment. We report on a systematic literature review, in which we found that the use of IPTW has increased rapidly in recent years, but that in the most recent year, a majority of studies did not formally examine whether weighting balanced measured covariates between treatment groups. We then proceed to describe a suite of quantitative and qualitative methods that allow one to assess whether measured baseline covariates are balanced between treatment groups in the weighted sample. The quantitative methods use the weighted standardized difference to compare means, prevalences, higher‐order moments, and interactions. The qualitative methods employ graphical methods to compare the distribution of continuous baseline covariates between treated and control subjects in the weighted sample. Finally, we illustrate the application of these methods in an empirical case study. We propose a formal set of balance diagnostics that contribute towards an evolving concept of ‘best practice’ when using IPTW to estimate causal treatment effects using observational data. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
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              Symptoms of Anxiety or Depressive Disorder and Use of Mental Health Care Among Adults During the COVID-19 Pandemic — United States, August 2020–February 2021

              The spread of disease and increase in deaths during large outbreaks of transmissible diseases is often associated with fear and grief ( 1 ). Social restrictions, limits on operating nonessential businesses, and other measures to reduce pandemic-related mortality and morbidity can lead to isolation and unemployment or underemployment, further increasing the risk for mental health problems ( 2 ). To rapidly monitor changes in mental health status and access to care during the COVID-19 pandemic, CDC partnered with the U.S. Census Bureau to conduct the Household Pulse Survey (HPS). This report describes trends in the percentage of adults with symptoms of an anxiety disorder or a depressive disorder and those who sought mental health services. During August 19, 2020–February 1, 2021, the percentage of adults with symptoms of an anxiety or a depressive disorder during the past 7 days increased significantly (from 36.4% to 41.5%), as did the percentage reporting that they needed but did not receive mental health counseling or therapy during the past 4 weeks (from 9.2% to 11.7%). Increases were largest among adults aged 18–29 years and among those with less than a high school education. HPS data can be used in near real time to evaluate the impact of strategies that address mental health status and care of adults during the COVID-19 pandemic and to guide interventions for groups that are disproportionately affected. HPS is a rapid-response online survey using a probability-based sample design to measure the social and economic impact of the COVID-19 pandemic on U.S. households ( 3 ). This experimental data product* was developed by the U.S. Census Bureau in partnership with CDC’s National Center for Health Statistics (NCHS) and several other federal statistical agencies. The sample is drawn from the U.S. Census Bureau’s Master Address File. † E-mail addresses and mobile telephone numbers associated with randomly selected housing units are used to invite participants. Analytic files include self-reported data from one adult aged ≥18 years at each address. Data collection began on April 23, 2020, and is ongoing (phase 1 = April 23–July 21, 2020; phase 2 = August 19–October 26, 2020; phase 3 = October 28, 2020–present, with a break during December 22, 2020–January 5, 2021). HPS response rates averaged 2.9%, 9.3%, and 6.5% during phase 1, phase 2, and phase 3 (through February 1, 2021), respectively. Questions on mental health symptoms were based on the validated four-item Patient Health Questionnaire (PHQ-4) for depression and anxiety and included how often, during the past 7 days, respondents had been bothered by 1) feeling nervous, anxious, or on edge; 2) not being able to stop or control worrying; 3) having little interest or pleasure in doing things; and 4) feeling down, depressed, or hopeless. Adults who had symptoms that generally occurred more than one half of the days or nearly every day were classified as having symptoms, consistent with published scoring recommendations § ( 4 ). Questions about mental health care use included whether, during the past 4 weeks, respondents had 1) taken prescription medication for their mental health, 2) received counseling or therapy from a mental health professional, or 3) needed but did not receive counseling or therapy from a mental health professional (i.e., had an unmet mental health need). Because of methodological differences between phases 1 and 2, trend analyses were limited to phases 2 and 3. ¶ Estimates** are presented for each 2-week data collection period for August 19, 2020–February 1, 2021 (unweighted sample size = 431,656 for phase 2 and 358,977 for phase 3, total = 790,633). Trends were assessed using joinpoint regression. †† In addition, changes in estimates of symptoms of an anxiety or a depressive disorder and the two mental health care measures were compared between August 19–31, 2020, and January 20–February 1, 2021, according to selected respondent characteristics. SAS-callable SUDAAN (version 11.0; RTI International) was used to conduct these analyses. Estimates were weighted to adjust for nonresponse and number of adults in the household and to match U.S. Census Bureau estimates of the population by age, sex, race/ethnicity, and educational attainment. During August 19–31, 2020, through December 9–21, 2020, significant increases were observed in the percentages of adults who reported experiencing symptoms of an anxiety disorder (from 31.4% to 36.9%), depressive disorder (from 24.5% to 30.2%), and at least one of these disorders (from 36.4% to 42.4%) (Figure 1). Estimates for all three mental health indicators through January 2021 were similar to those in December 2020. FIGURE 1 Percentage of adults aged ≥18 years with symptoms of anxiety disorder, depressive disorder, or anxiety or depressive disorder during past 7 days, by data collection period — Household Pulse Survey, United States, August 19, 2020–February 1, 2021* * Household Pulse Survey data collection included a 1-day break between the conclusion of one data collection period and the start of the next, as well as a 2-week break during December 22, 2020–January 5, 2021. This figure is a line graph showing the percentage of adults aged ≥18 years with symptoms of anxiety disorder, depressive disorder, or anxiety or depressive disorder during the past 7 days in the United States during August 19, 2020 through February 1, 2021. During August 19–31, 2020, through November 25–December 7, 2020, a significant increase was observed in the percentage of adults who reported taking prescription medication or receiving counseling for their mental health (from 22.4% to 25.0%) (Figure 2). Similarly, during August 19–31, 2020, through December 9–21, 2020, a significant increase was observed in the percentage of adults who reported needing but not receiving counseling or therapy for their mental health (from 9.2% to 12.4%). Estimates through January 2021 were similar to those in December 2020. FIGURE 2 Percentage of adults aged ≥18 years who took prescription medication for mental health or received counseling or therapy during past 4 weeks and percentage who needed but did not receive counseling or therapy during past 4 weeks, by data collection period — Household Pulse Survey, United States, August 19, 2020–February 1, 2021* * Household Pulse Survey data collection included a 1-day break between the conclusion of one data collection period and the start of the next, as well as a 2-week break during December 22, 2020–January 5, 2021. This figure is a line graph showing the percentage of adults aged ≥18 years who took prescription medication for mental health or received counseling or therapy during past 4 weeks and percentage who needed but did not receive counseling or therapy during past 4 weeks in the United States during August 19, 2020 through February 1, 2021. During August 19–31, 2020, through January 20–February 1, 2021, symptoms of an anxiety or a depressive disorder increased significantly from 36.4% to 41.5% (Table). Significant increases were observed for all demographic subgroups presented, except adults aged ≥80 years and non-Hispanic adults reporting races other than White, Black, or Asian. The largest increases (8.0 and 7.8 percentage points) were among those aged 18–29 years and those with less than a high school education, respectively. During this time, mental health care treatment increased significantly from 22.4% to 24.8%. Significant increases were observed for adults aged 18–29, 30–39, and 60–69 years; men and women; non-Hispanic White and non-Hispanic Black adults; adults with at least a high school education; and adults who had not experienced symptoms of an anxiety or a depressive disorder during the past 7 days. TABLE Weighted* percentage of adults aged ≥18 years with symptoms of anxiety or depressive disorder during past 7 days, percentage who took prescription medication for mental health or received counseling or therapy during past 4 weeks, and percentage who needed but did not receive counseling or therapy during past 4 weeks, by selected characteristics — Household Pulse Survey, United States, August 19, 2020–February 1, 2021 Characteristic % (95% CI) Symptoms of anxiety or depressive disorder during past 7 days Took prescription medication for mental health or received counseling or therapy during past 4 weeks Needed but did not receive counseling or therapy during past 4 weeks Aug 19–31, 2020 Jan 20–Feb 1, 2021 Aug 19–31, 2020 Jan 20–Feb 1, 2021 Aug 19–31, 2020 Jan 20–Feb 1, 2021 Total 36.4 (35.9–36.9) 41.5 (40.7–42.2)† 22.4 (22.0–22.9) 24.8 (24.2–25.4)† 9.2 (8.8–9.6) 11.7 (11.1–12.2)† Age group, yrs 18–29 49.0 (47.5–50.5) 57.0 (54.2–59.8)† 23.3 (21.5–25.2) 26.9 (24.9–29.0)† 15.6 (14.5–16.7) 22.8 (20.3–25.4)† 30–39 42.5 (40.8–44.1) 45.9 (44.5–47.3)† 23.1 (22.1–24.1) 27.1 (25.8–28.4)† 12.9 (11.9–13.9) 16.1 (14.8–17.5)† 40–49 37.6 (36.3–39.0) 41.1 (38.9–43.2)† 23.6 (22.8–24.5) 25.0 (23.7–26.3) 10.0 (9.3–10.7) 11.0 (10.0–11.9) 50–59 34.9 (33.6–36.3) 41.2 (39.8–42.6)† 23.9 (22.8–25.1) 25.4 (24.0–26.9) 7.7 (6.9–8.5) 9.5 (8.6–10.4)† 60–69 29.3 (28.0–30.6) 33.4 (31.6–35.4)† 21.2 (20.2–22.2) 23.3 (22.0–24.6)† 5.3 (4.8–5.9) 5.4 (4.8–6.0) 70–79 23.2 (21.6–25.0) 26.3 (24.6–28.0)† 19.6 (18.1–21.1) 19.8 (18.3–21.3) 2.9 (2.2–3.6) 3.1 (2.4–3.9) ≥80 19.4 (16.3–22.9) 22.5 (18.5–27.0) 14.8 (12.0–17.9) 17.3 (14.1–21.0) 1.4 (0.9–2.0) 2.3 (1.3–3.7) Sex Male 31.8 (30.8–32.8) 38.0 (36.9–39.1)† 16.3 (15.6–17.1) 19.1 (18.1–20.1)† 6.8 (6.2–7.3) 9.1 (8.3–9.8)† Female 40.7 (39.9–41.5) 44.8 (43.8–45.8)† 28.0 (27.3–28.7) 30.0 (29.3–30.7)† 11.4 (10.9–11.9) 14.1 (13.4–14.8)† Race/Ethnicity Hispanic or Latino 40.2 (38.0–42.3) 47.1 (44.7–49.4)† 17.2 (15.8–18.6) 19.5 (17.3–21.9) 9.6 (8.6–10.6) 12.8 (10.9–14.9)† White, non-Hispanic 35.4 (34.8–35.9) 39.8 (38.9–40.7)† 25.6 (25.0–26.1) 28.1 (27.3–28.8)† 9.1 (8.7–9.5) 11.7 (11.2–12.1)† Black, non-Hispanic 37.7 (35.7–39.8) 44.5 (41.6–47.5)† 15.6 (14.2–17.1) 18.7 (16.7–20.8)† 9.3 (8.3–10.3) 12.2 (10.4–14.1)† Asian, non-Hispanic 30.5 (28.2–32.8) 37.4 (33.4–41.5)† 11.1 (9.7–12.5) 12.9 (10.7–15.4) 4.8 (3.9–5.8) 5.8 (4.5–7.3) Other/Multiple races, non-Hispanic 43.1 (40.2–46.1) 44.8 (41.0–48.6) 25.0 (22.3–27.9) 23.8 (20.9–26.9) 14.2 (12.1–16.4) 13.8 (11.4–16.5) Education level Less than high school diploma 41.8 (38.4–45.2) 49.6 (45.7–53.5)† 20.0 (17.3–22.9) 20.6 (17.5–24.0) 7.0 (5.4–8.8) 11.3 (8.8–14.2)† High school diploma or GED certificate 36.3 (35.0–37.7) 41.1 (39.3–42.9)† 20.1 (19.1–21.2) 22.2 (20.9–23.4)† 7.0 (6.3–7.8) 8.7 (7.4–10.2)† Some college or associate’s degree 39.4 (38.5–40.3) 46.4 (45.2–47.6)† 23.5 (22.7–24.4) 27.7 (26.8–28.7)† 11.2 (10.6–11.9) 14.9 (13.9–15.9)† Bachelor’s degree or higher 32.4 (31.7–33.0) 35.5 (34.7–36.3)† 24.0 (23.4–24.6) 25.4 (24.6–26.1)† 9.7 (9.2–10.1) 11.4 (10.9–12.0)† Symptoms of anxiety or depressive disorder during past 7 days Did not experience symptoms NA NA 13.9 (13.4–14.4) 15.6 (14.9–16.4)† 2.4 (2.2–2.7) 3.1 (2.8–3.5)† Experienced symptoms NA NA 37.5 (36.5–38.5) 37.7 (36.6–38.8) 21.0 (20.2–21.8) 23.8 (22.8–24.9)† Abbreviations: CI = confidence interval; GED = general educational development; NA = not applicable. * Estimates were weighted to adjust for nonresponse and number of adults in the household and to match U.S. Census Bureau estimates of the population by age, sex, race/ethnicity, and educational attainment. † Significant difference between percentages at two time points (August 19–31, 2020, versus January 20–February 1, 2021) based on two-sided significance tests at the 0.05 level. Unmet mental health needs also increased significantly from 9.2% to 11.7%. Subgroups with significant increases included adults aged 18–29, 30–39, and 50–59 years; men and women; Hispanic, non-Hispanic White, and non-Hispanic Black adults; adults at all education levels; and adults regardless of whether they experienced symptoms of an anxiety or a depressive disorder or both during the past 7 days. The largest increases in unmet mental health needs (7.2 percentage points and 4.3 percentage points) were among adults aged 18–29 years and those with less than a high school education, respectively. During January 20, 2021–February 1, 2021, 23.8% of persons with symptoms of an anxiety or a depressive disorder had unmet mental health needs, and this percentage increased by 2.8 percentage points from August 2020 to February 2021. Discussion The percentage of adults who had symptoms of an anxiety or a depressive disorder during the past 7 days and those with unmet mental health needs during the past 4 weeks increased significantly from August 2020 to February 2021, with the largest increases among those aged 18–29 years and those with less than a high school education. During January 20, 2021–February 1, 2021, more than two in five adults aged ≥18 years experienced symptoms of an anxiety or a depressive disorder during the past 7 days. One in four adults who experienced these symptoms reported that they needed but did not receive counseling or therapy for their mental health. These findings are consistent with results from surveys conducted early in the COVID-19 pandemic (March–June 2020) that showed an increased prevalence of mental health symptoms, especially among young adults ( 5 – 7 ). The more recent results indicate an increasing prevalence over time later in 2020, which remained increased in early 2021. The trends in symptoms of an anxiety or a depressive disorder from HPS have been shown to be consistent with trends in the weekly number of reported COVID-19 cases, and it has been theorized that increases in these mental health indicators correspond with pandemic trends ( 8 ). The findings in this report are subject to at least four limitations. First, these data are based on self-report and were not confirmed by health professionals. Questions about mental health symptoms might be predictive of but do not necessarily reflect a clinical diagnosis. In addition, the predictive validity of the scales used in this report have not been confirmed when adapted from a 2-week to a 1-week time frame. Second, HPS did not assess the cause of these symptoms; therefore, a direct association with COVID-19 events could not be determined with certainty. Third, changes in mental health symptoms from the summer to the winter months might reflect symptoms associated with seasonal affective disorder ( 9 ). However, data from the 2019 National Health Interview Survey (NHIS), §§ measured using the unmodified PHQ-4, did not demonstrate statistically significant changes from August to December 2019 for symptoms of an anxiety disorder (8.1% to 8.6%); a depressive disorder (7.0% to 6.7%); or an anxiety disorder, a depressive disorder, or both (11.0% to 11.3%) ( 10 ). Finally, these estimates are intended to represent all adults aged ≥18 years living in housing units in the United States. However, representativeness might be limited by the indirect exclusion of persons without Internet access and by low response rates. Some households were not eligible to participate because the U.S. Census Bureau was unable to match a mobile telephone number or e-mail address. The sampling weights that were applied to all analyses were likely to have reduced some of the potential bias. Nevertheless, these data might not fully meet the U.S. Census Bureau’s quality standards and as such, the bureau labeled these data as experimental. Despite these limitations, the survey’s timeliness and relevance are strengths of HPS. The U.S. Census Bureau releases data tables to the public 9 days after the close of each data collection period. ¶¶ Simultaneously, NCHS updates online visualizations of trends in key health indicators.*** Several measures have been initiated to address increased mental health risks associated with COVID-19, ††† and a previous report outlines additional strategies, including expanded use of telehealth, to address mental health conditions during the pandemic ( 6 ). Continued near real-time monitoring of mental health trends by demographic characteristics is critical during the COVID-19 pandemic. These trends might be used to evaluate the impact of strategies that address mental health status and care of adults during the pandemic and to guide interventions for groups that are disproportionately affected. Summary What is already known about this topic? Large disease outbreaks have been associated with mental health problems. What is added by this report? During August 2020–February 2021, the percentage of adults with recent symptoms of an anxiety or a depressive disorder increased from 36.4% to 41.5%, and the percentage of those reporting an unmet mental health care need increased from 9.2% to 11.7%. Increases were largest among adults aged 18–29 years and those with less than a high school education. What are the implications for public health practice?  Trends in mental health can be used to evaluate the impact of strategies addressing adult mental health status and care during the pandemic and to guide interventions for disproportionately affected groups.
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                Author and article information

                Contributors
                Journal
                Hepatol Commun
                Hepatol Commun
                HC9
                Hepatology Communications
                Lippincott Williams & Wilkins (Hagerstown, MD )
                2471-254X
                April 2023
                30 March 2023
                : 7
                : 4
                : e0129
                Affiliations
                [1 ]Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
                [2 ]Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
                [3 ]Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
                [4 ]Division of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA
                [5 ]VA Connecticut Healthcare System, West Haven, Connecticut, USA
                [6 ]Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
                [7 ]Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
                Author notes
                Correspondence Nadim Mahmud, Civic Center Boulevard, 4th Floor, South Pavilion, Philadelphia, PA 19104, USA. Email: nadim@ 123456pennmedicine.upenn.edu
                Author information
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                Article
                00037
                10.1097/HC9.0000000000000129
                10069831
                36996031
                642b62c4-8636-4e65-b822-12bb7d874457
                Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/

                History
                : 5 December 2022
                : 24 February 2023
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