Background

Patients with multiple long-term conditions, i.e., multimorbidity, are frequent users of services in all healthcare sectors [1,2,3]. Despite increased healthcare delivery, they report impaired daily functioning, poor quality of life, and adverse health outcomes [4,5,6,7]. For these patients, the coordination of care is often complicated by the high number of clinicians involved in their treatment, including multiple appointments, involvement of both primary care and specialists in secondary care, repeated referrals, and parallel outpatient trajectories with duplicate services in a highly specialized healthcare system [1, 8]. This may lead to inadequate transfer of information, unclear treatment responsibilities, and ultimately fragmented healthcare. Care fragmentation produces adverse consequences, including economic inefficiency, inequality in health, and depersonalization of the patient [9]. Furthermore, poor continuity of care has also been linked to more hospital admissions, inappropriate medication use, and increased mortality [10,11,12,

Table 1 Measures of cross-sectoral care fragmentation

Additionally, we included formal fragmentation indices, which provide a mathematical quantification of different aspects of fragmentation [30, 38,39,40,41]: (1) the Usual Provider of Care Index (UPC) which describes the concentration of contacts with a single provider, (2) the Bice-Boxerman Continuity of Care Index (COCI) which describes the distribution of care among providers, and (3) the Sequential Continuity Index (SECON) which describes the number of contacts to the provider whom the patient visited most recently (see Table 1 for details) [30, 42]. Additionally, we constructed the Known GP Index by calculating the proportion of contacts to the patient’s own GP clinic out of all healthcare contacts. All these indices ranged from 0 to 1, with lower values indicating a higher degree of care fragmentation. To ensure the robustness of the indices, at least four healthcare contacts were required to calculate the indices as recommended by Rosenberg et al. [43].

Outcomes

We had two main outcomes. The first, potentially inappropriate medication (PIM), was chosen as a clinical indicator of quality of care as it assesses days with potentially suboptimal medication regimes and is associated with adverse health outcomes such as emergency hospital admission [44]. It was based on a modified version of the STOPP/START criteria [45], which are used clinically and in pharmacoepidemiologic research to identify potentially inappropriate drug-drug and drug-disease combinations, e.g., stop concomitant use of drugs with anticholinergic properties or prolonged benzodiazepine use (STOPP criteria), or combinations that would suggest medication initiation, e.g., start antiplatelet therapy in patients with a history of coronary disease (START criteria). These criteria were adapted for an adult population in a Danish register-based setting through an iterative consensus group process, which resulted in the selection of 29 STOPP criteria. The process is described in detail elsewhere [46]. During the same process, 10 START criteria were also selected (Additional file 1: Methods S3). The process resulted in an algorithm to identify the periods of time when an individual was subject to PIM by combining data on redeemed drug prescriptions and diagnoses from the Danish registers. Patients may have contributed with PIM time more than once if being subjected to multiple concurrent PIMs for up to a maximum of the 1-year study period. Time with PIM was assessed between 1 January 2018 and 31 December 2018.

The second outcome, all-cause mortality, was chosen as an overall indicator of patient prognosis. Death was assessed during follow-up as recorded in the Danish Civil Registration System between 1 January 2018 and 31 December 2018 [34].

Statistical analyses

Clinical indicators of care fragmentation were categorized into groups by count. Formal fragmentation indices were divided into groups with 0.25 increments from 0 to 1. Care fragmentation measures were presented as means and group distribution by the number of comorbid conditions.

Negative binomial regression models were used to estimate incidence rate ratios (IRR) with 95% confidence intervals (CIs) of total PIM time (sum of days for each PIM criteria), accounting for time at risk. A first model was adjusted for age group and sex. A second model was further adjusted for cohabitation status, country of origin, educational attainment according to the UNESCO educational level, OECD-adjusted household income, population density (urban vs rural areas), and presence of each of the 39 conditions in the Danish Multimorbidity Index.

Cox regression models were used to estimate all-cause mortality hazard ratios (HR) with 95% CIs, with age as the underlying time axis. Two models were constructed, with similar adjustments as in the models for PIM. Absolute terms were obtained as cumulative incidence proportions (CIP).

To visualize the functional form of the formal fragmentation indices, a restricted cubic spline model, covering the full range of values, was added with five knots using Harrell’s default percentiles.

The analyses were stratified on disease count at baseline to assess interactions between disease burden and care fragmentation. A sensitivity analysis was performed to examine individual STOPP/START criteria items.

All analyses were performed with Stata 17. The reporting of this study followed the STROBE guidelines.