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Supplemental Digital Content Study Protocol: Longitudinal course of depressive, anxiety and post-traumatic stress disorder symptoms after heart surgery Review question What is the longitudinal course of depressive, anxiety, and post-traumatic stress-disorder (PTSD) symptoms in cardiac patients undergoing heart surgery? Searches PubMed and Scopus, up to 07/31/2019, search key: ("implantable cardiac defibrillator" OR "cardiac operation" OR "heart surgery" OR "cardiac surgery" OR "coronary artery bypass" OR "open heart surgery" OR "valve surgery" OR “heart transplant*”) AND ((("depression" OR "depressive") AND "episode") OR "major depressive disorder" OR "anxiety" OR "PTSD" OR "post-traumatic stress disorder" OR "acute stress- reaction" OR "quality of life"). The Preferred Reporting Items for Systematic RevieWs and Meta-analyses (PRISMA) recommendations will be used to guide this meta-analysis. (1) Inclusion criteria Cohort studies measuring depressive, anxiety, or PTSD symptoms with validated psychometric tools, before and at least 1 month after heart surgery. Exclusion criteria Article type different from cohort study (interventional, revieW article, meta-analysis, editorial, conference abstract, case report). Language other than English. Publication date antecedent to 1980. Population Cardiac patients scheduled for heart surgery. Exposure Cardiac surgery, whether first time or more. Comparator Post-surgical depressive, anxiety, and PTSD symptoms, whether reported as mean scores or rates by the authors, will be compared with the pre-surgical levels in the same study population. Primary outcome Primary outcome Will be the pre-post change in depressive, anxiety, and PTSD symptoms folloWing surgery, measured as standardized effect size. Secondary Outcomes Secondary outcomes Will be: 1) the durability of mental health symptom changes; 2) the correlation betWeen baseline demographic and clinical characteristics and improvement in mental health scores. Strategy for data synthesis A random-effects meta-analysis of pre-post changes in the mental health symptoms assessed with psychometric tools will be performed. A pre-post correlation coefficient of 0.5 if not otherwise specified will be assumed. Binary and continuous outcomes Will be pooled together. Subgroup analyses will be performed for: type of heart surgery; studies that included subjects with psychiatric disorders at baseline or not; among regions; among subjects undergoing HS for the first time or more; among folloW-up duration ranges (1-3 months, ≥3-6 months, ≥6-12 months , >1 year); and among modalities for reporting the outcome (binary versus continuous). Moderators to investigate with meta-regression will be mean age, % married, % white, % males, % with specific medical comorbidities, and % smoking. Quality assessment Quality of cohort studies will be assessed with Newcastle-OttaWa Scale. (2) Bibliography 1. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. In: J. Clin. Epidemiol. 2009. p. e1–34. 2. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Al. E. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. Ottawa Hospital Research Institute, editor. Ottawa; Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp2017. Supplementary figure 1. Forest plot of Depressive symptoms studies Supplementary figure 2. Forest plot of Anxiety symptoms studies Supplementary figure 3. Forest plot of PTSD symptoms Legend. PTSD, Post-Traumatic Stress Disorder. Supplementary figure 4. Funnel plot of Depressive symptoms studies Supplementary figure 5. Funnel Plot of Anxiety symptoms studies Supplementary figure 6. Funnel plot of PTSD symptoms studies Legend. PTSD, Post-traumatic stress disorder. Supplementary table 1. Characteristics of included studies Main Depression Anxiety Assessment cardiac Follow- PTSD Assessment Tool Surgery Mean Additional Characteristics in Assessment Tool Tool Study Country condition N up (Criteria for procedure age Subgroups (Criteria for (Criteria for for (months) dichotomous outcome) dichotomous outcome) dichotomous outcome) surgery AbuRuz, 2019 HADS (2) Jordan CABG CAD 227 66.1 1.5 - - - (1) (HADS ≥8) Baranyi, 2013 PTSS-10 (4) Germany HT HF 62 54.4 24.9 - - - (3) (PTSS-10 ≥35) CAD, HARS (6) Bech , 1984 (5) Denmark Mixed valve 30 54.0 6 - - - disease Bidwell, 2017 VAD USA HF 41 53.8 3 - PHQ-8 (8) BSI (9) - (7) Implantation Blumenthal, CES-D (11) USA CABG CAD 817 61.0 6 - - - 2003 (10) (CES-D ≥16) Borowicz, 2002 CES-D (11) USA CABG CAD 172 63.4 60 - - - (12) (CES-D ≥16) Botzet, 2017 Mitral valve Valve HADS (2) HADS (2) Germany 100 64.6 6 - - (13) surgery disease (HADS ≥8) (HADS ≥8) 1. No pre-surgical depression (N 64) BDI (15) Burg, 2003 (14) USA CABG CAD 89 65.9 6 - - 2. Presurgical depression (BDI≥10) (N 25) 1 Main Depression Anxiety Assessment cardiac Follow- PTSD Assessment Tool Surgery Mean Additional Characteristics in Assessment Tool Tool Study Country condition N up (Criteria for procedure age Subgroups (Criteria for (Criteria for for (months) dichotomous outcome) dichotomous outcome) dichotomous outcome) surgery (Depression was assessed with BDI according to authors’ criteria) (15) CAD, Burker, 1995 USA Mixed valve 247 61.0 1.5 - CES-D (11) HADS (2) - (16) disease CAD, Chunta, 2009 HADS (2) HADS (2) USA Mixed valve 54 63.5 1 - - (17) (HADS ≥8) (HADS ≥8) disease Connolly, 2004 Mixed DISC (19) USA Mixed 43 8.2 1.5 - - - (18) conditions (Anxiety Module) SCA/Ventr DSM-III-R SCID (21) ICD DSM-III-R SCID (21) Crow, 1998 (20) USA icular 35 N/A 12.3 - (Panic Disorder - implantation (MDD module) arrhythmia module) 1. Non-Type D CAD, Dannemann, personality before HADS (2) HADS (2) Germany Mixed valve 126 67.0 6 - 2010 (22) and after surgery (N disease 77) 2 Main Depression Anxiety Assessment cardiac Follow- PTSD Assessment Tool Surgery Mean Additional Characteristics in Assessment Tool Tool Study Country condition N up (Criteria for procedure age Subgroups (Criteria for (Criteria for for (months) dichotomous outcome) dichotomous outcome) dichotomous outcome) surgery 2. Type D personality only before surgery (N 19) 3. Type D personality only after surgery (N 16) 4. Type D personality before and after surgery (N 14) (Type D personality was assessed with DS14) (23) Deshields, 1996 - USA HT HF 10 50.3 12 BDI (15) BAI (25) - (24) Doering, 2006 DISH (27) USA CABG CAD 55 62.5 6 - - - (26) (MDD module) CAD, Doering, 2014 BDI (15) USA Mixed valve 251 67.3 1.5 - - - (28) (BDI ≥10) disease Netherland Duits, 1999 (29) CABG CAD 217 60.8 6 - HADS (2) STAI (30) - s 3 Main Depression Anxiety Assessment cardiac Follow- PTSD Assessment Tool Surgery Mean Additional Characteristics in Assessment Tool Tool Study Country condition N up (Criteria for procedure age Subgroups (Criteria for (Criteria for for (months) dichotomous outcome) dichotomous outcome) dichotomous outcome) surgery Edéll- SSAI (30) Zung’s SDS (32) Gustafsson, Sweden CABG CAD 38 61.3 6 - - (SSAI ≥43) (Zung’s SDS ≥50) 1999 (31) CAD, Egan, 1998 (33) UK Mixed valve 55 63.5 2 - - SSAI (30) - disease Eremina, 2017 Russia CABG CAD 70 59.7 3 - - ITT (35) - (34) Eriksson, 1988 BDI (15) HARS (6) Finland CABG CAD 101 52.2 7.5 - - (36) (BDI ≥14) (HARS ≥11) Fisher, 1995 USA HT HF 94 53 60 - BDI (15) - - (37) CAD, Geulayov, 2018 HADS (2) HADS (2) Israel Mixed valve 1125 65.7 12 - - (38) (HADS ≥8) (HADS ≥8) disease CAD, BDI (15) Goyal, 2005 (39) USA Mixed valve 90 66.0 6 - - - (BDI ≥9) disease DSM-IV SCID (41) Grigioni, 2005 Italy HT HF 127 52 12 - (MDD + Dysthymic - - (40) Disorder modules) 4 Main Depression Anxiety Assessment cardiac Follow- PTSD Assessment Tool Surgery Mean Additional Characteristics in Assessment Tool Tool Study Country condition N up (Criteria for procedure age Subgroups (Criteria for (Criteria for for (months) dichotomous outcome) dichotomous outcome) dichotomous outcome) surgery Grossi, 1998 Sweden CABG CAD 61 66.0 12 - - STAI (30) - (42) 1. Female (N 41) Guzelhan, 2018 Turkey CABG CAD 137 68.2 6 2. Male (N 96) - STAI (30) - (43) Hallas, 2003 HADS (2) HADS (2) UK CABG CAD 22 62.0 2 - - (44) (HADS ≥8) (HADS ≥8) CAD, 1. Age ≥ 75 (N 200) Heijmeriks, Netherland Mixed valve 600 69.3 6 2. Age <75 (N 400) HADS (2) HADS (2) - 1999 (45) s disease Höfer, 2006 (46) Austria CABG CAD 121 63.1 3 - HADS (2) HADS (2) - 1. “Depression” at baseline per authors’ criteria (N 104) 2. "At risk" for PHQ-9 (8) Horne, 2013 Canada Mixed CAD 436 65.5 6 depression at baseline (PHQ>9, or PHQ 5-9 - - (47) per authors’ criteria with>3 items) (N 167) 3. "Naive" to depression at baseline per 5 Main Depression Anxiety Assessment cardiac Follow- PTSD Assessment Tool Surgery Mean Additional Characteristics in Assessment Tool Tool Study Country condition N up (Criteria for procedure age Subgroups (Criteria for (Criteria for for (months) dichotomous outcome) dichotomous outcome) dichotomous outcome) surgery authors’ criteria (N 165) 1. Undergoing CABG (N 60) 2. Undergoing valve CAD, Hoyer, 2008 replacement (N 22) Germany Mixed valve 90 66.9 6 HADS (2) HADS (2) - (48) 3. Undergoing disease combined surgery (CABG and valve replacement) (N 8) Jenkins, 1983 (a) USA CABG CAD 318 54.4 6 - - SSAI (30) - (49) CAD, Jenkins, 1983 USA Mixed valve 89 56.8 6 - - SSAI (30) - (b) (50) disease Jones, 1992 (51) Australia HT HF 27 44.6 50 - BDI (15) STAI (30) - Karapolat, 2007 Turkey HT HF 34 41.4 19.3 - BDI (15) STAI (30) - (52) Khatri, 2001 1. Surgery with CES-D (11) STAI (30) USA CABG CAD 226 61.5 6 - (53) hypothermia (N 111) (CES-D ≥16) (STAI ≥45) 6 Main Depression Anxiety Assessment cardiac Follow- PTSD Assessment Tool Surgery Mean Additional Characteristics in Assessment Tool Tool Study Country condition N up (Criteria for procedure age Subgroups (Criteria for (Criteria for for (months) dichotomous outcome) dichotomous outcome) dichotomous outcome) surgery 2.