3.1 Study selection
The combined PubMed and Embase searches yielded 4765 unique records. After abstract review, 57 full-text articles were assessed for eligibility, of which 23 fulfilled our selection criteria. The other 34 were excluded for the following reasons: 25 studies did not provide relevant data on the topic under study; four studies were not identified as case management interventions; two studies dealt with a different health population; two studies did not include original data; and one study presented the same cohort. Two further studies [29, 34] were identified through cross-reference checking and two study [27, 35] was added through verification search, bringing the total to 27 included studies. Figure 1 provides an overview of the search and study selection process.
3.2 Study characteristics
Tables 2 describes the characteristics of the included studies. Of the 27 studies included, 23 [24-26, 28-30, 34-50] were RCTs and four were non-randomized intervention studies [27, 51-53]. The studies were published between 2002 and 2020 and evaluated case management interventions in various countries. The majority of studies evaluated case management interventions among patients with a single health condition [24-30, 36-39, 41-43, 45, 46, 48-53] whereas five studies [34, 35, 40, 44, 47] included patients with two or more different chronic diseases, such as heart failure and/or asthma or COPD. Only one of the included studies was conducted among people with PD. Taken together, the studies included 3752 participants ascribed to case management interventions. Mean age ranged from 57 years to 80 years, with an average age across all studies of 65 years, with 51% being female among the 25 studies [24-29, 34-53] reporting gender. 3682 participants were ascribed to the usual care group. Mean age ranged from 51 years to 78 years with an average age across all studies of 51 years, and also here with 51% being women.
3.3 Risk of bias and quality assessment
Of the four non-randomized intervention studies, three were rated as carrying a high risk of bias and one as a moderate risk. Of the RCTs, only eight studies [24, 29, 34, 35, 37, 38, 40, 49] were judged to be of a good methodological quality and at low risk of carrying bias. The remaining 15 studies were of low or moderate quality with a high or unknown risk of bias among several domains. However, most RCTs were rated as having a high or unknown risk on the domains of blinding of participants and blinding of outcome assessment, which is less applicable to this kind of intervention. Details on the quality assessment are presented in Supplemental Data II.
3.4 Components of case management intervention
Across the 27 included studies, there was substantial heterogeneity across the content and duration of the various case management interventions. Table 3 displays the different strategies used in each study. Common components of case management among the 27 studies (i.e., applied in at least … studies) were (1) regular telephone contacts combined with in-person visits; (2) monitoring of signs, symptoms and risk factors; (3) ensuring therapy adherence; and (4) providing educational support on disease management and treatment, or trainings on self-management skills. However, the content and structure of these components varied highly among these studies. For instance, the purpose of in-person home visits ranged from developing and discussing a therapeutic plan with the patient in one study [41], to monitoring changes in signs and symptoms as well as reviewing patient’s safety in their own home environment in another study [37]. The location of in-person visits also varied from the patient’s home to a clinical setting. Most studies were conducted through a combination of in-person and telephone contacts, with only seven studies [25, 27, 38, 42, 45, 46, 52] reporting an intervention that was exclusively conducted through telephone contact.
Providing assistance for social and financial support, organization of multidisciplinary case meetings, medication review and the development of individualized care plans were more commonly reported case management interventions. In only four studies, case management interventions also included the support of informal carers [25, 26, 35, 36]. And of these, only one study included a regular assessment of the carer’s physical health and provision of education on carer’s coping skills, in addition to educating carers on disease management [36].
Furthermore, several studies incorporated the use of technological support systems which not only supported the implementation of case management strategies, but also offered new possibilities. For instance, a web-based service facilitated communication between the patient and the care team, to schedule patient contacts and to keep track of progress and current disease treatment [36]. In a different study, a web-based collaborative intervention facilitated peer-to-peer support for patients with cancer through a chat room connecting all enrolled participants to each other [30].
Of the 27 studies, 23 [25-28, 30, 34-45, 48-53] reported that case management interventions were delivered by a nurse case manager or a team consisting of a nurse case manager and other health care specialists. In one study [29] the case manager was a depression clinical specialist without further clarification of the background of the specialist and in another one [24] two research coordinators fulfilled the role as care managers. In the other two studies the background of the case manager was not specified any further [46, 47]. Length of follow-up ranged from one and a half month to 24 months, with 18 studies reporting a 12-month or even longer follow-up period (Table 2).
3.5 Overview of outcome measurements
Results of the narrative data synthesis are summarized and presented in Table 2. Nearly all included studies evaluated the effectiveness of case management interventions on depressive symptoms, whereas anxiety was addressed in only eight studies [25, 28, 41, 43, 46-48, 51]. None of the included studies reported on falls, urinary tract infections, swallowing impairment or hallucinations.
3.5.1 Effect of case management on anxiety
Eight studies (n = 1239 participants) reported outcomes on symptoms of anxiety [25, 28, 41, 43, 46-48, 51]. The most commonly used scale was the Hospital Anxiety and Depression Scale (HADS) [25, 28, 41, 43, 46, 48], followed by 7-item Generalized Anxiety Disorder [47], and State Trait Anxiety Index (STAI) [51]. Six studies reported sufficient data and were included in a random effects meta-analysis, the results of which revealed a significant effect of case management interventions in decreasing anxiety (Standardized Mean Difference [SMD]= - 0.47; 95% confidence interval [CI]: -0.69, -0.324 with moderate heterogeniety (I2 = 51.9%) (Figure 2).
Variance inflating factor (VIF) analysis showed no evidence of multicollinearity (all VIFs <5). A tendency of lower SMD was found for studies with a higher percentage females [standardized regression coefficient β=0.01, p value=0.05]. No significant effect was found for mean age of intervention group [β= 0.02, p=0.13] and number of components were [β=0.13, p=0.21].
3.5.2 Effect of case management on depressive symptoms
With the exception of one study [51], all studies (n=7314 participants) reported depressive symptoms measurements using a total of six depression scales, including the 9-item Patient Health Questionnaire (PHQ-9) [24, 26, 29, 37, 38, 40, 44, 45, 47, 50, 52, 53], the Hospital Anxiety/Depression Scale (HADS) [25, 28, 41, 43, 46, 48], the Center for Epidemiologic Studies Depression scale (CES-D) [30, 35, 39, 40], 20-item Symptom Checklist (SCL-20) [28, 34, 42, 50], the Cornell Scale for depression [36] and Taiwanese Depression Questionnaire [27].
Twenty studies reported sufficient data and were included in the meta-analysis (Figure 3). Two studies [40, 50] reported two different depression outcomes (CES-D/SCL-20 PHQ-9), but for analytical reasons only one (PHQ-9) was included in the meta-analysis. A random-effects meta-analyses revealed a significant effect of case management intervention on depression (SMD= - 0.48; CI: -0.71, -0.25), but heterogenity was high (I2 = 92.3%). A funnel plot and Egger’s test of funnel plot asymmetry (p = 0.57) showed no evidence for publication bias.
Variance inflating factor (VIF) analysis showed no evidence of multicollinearity (all VIFs<5). There were no significant population or disease characteristics: neurodegenerative diseases (reference: internal medicine diseases) [β=0.20, p = 0.80], mean age of intervention group [β= -0.01, p = 0.76] and percentage of females assigned to case management intervention [β=-0.01, p = 0.43]. Moreover, no significant effect was found for any of the individual case management components: development and review of individualized care plans [β= -0.60, p = 0.21]; in-person contact with the case manager [β=-0.09, p=0.89]; medication review [β= 0.39, p = 0.47]; provision of education on disease management and treatment [β=-0.08, p = 0.91]; self-management support [β=-0.24, p = 0.70]; support and training for healthcare providers [β=0.05, p = 0.92]; therapy adherence [β=0.73, p = 0.92] and use of evidence-based guidelines [β=0.27, p = 0.52].