Clustering care pathways of people with alcohol dependence using a data linkage of routine data in Bremen, Germany.

BACKGROUND: Although many individuals with alcohol dependence (AD) are recognized in the German healthcare system, only a few utilize addiction-specific treatment services. Those who enter treatment are not well characterized regarding their prospective pathways through the highly fragmented German healthcare system. This paper aims to (1) identify typical care pathways of patients with AD and their adherence to treatment guidelines and (2) explore the characteristics of these patients using routine data from different healthcare sectors. METHODS: We linked routinely collected register data of individuals with a documented alcohol-related diagnosis in the federal state of Bremen, Germany, in 2016/2017 and their addiction-specific health care: two statutory health insurance funds (outpatient pharmacotherapy for relapse prevention and inpatient episodes due to AD with and without qualified withdrawal treatment (QWT)), the German Pension Insurance (rehabilitation treatment) and a group of communal hospitals (outpatient addiction care). Individual care pathways of five different daily states of utilized addiction-specific treatment following an index inpatient admission due to AD were analyzed using state sequence analysis and cluster analysis. The follow-up time was 307 days (10 months). Individuals of the clustered pathways were compared concerning current treatment recommendations (1: QWT followed by postacute treatment; 2: time between QWT and rehabilitation). Patients' characteristics not considered during the cluster analysis (sex, age, nationality, comorbidity, and outpatient addiction care) were then compared using a multinomial logistic regression. RESULTS: The analysis of 518 individual sequences resulted in the identification of four pathway clusters differing in their utilization of acute and postacute treatment. Most did not utilize subsequent addiction-specific treatment after their index inpatient episode (n = 276) or had several inpatient episodes or QWT without postacute treatment (n = 205). Two small clusters contained pathways either starting rehabilitation (n = 26) or pharmacotherapy after the index episode (n = 11). Overall, only 9.3% utilized postacute treatment as recommended. CONCLUSIONS: A concern besides the generally low utilization of addiction-specific treatment is the implementation of postacute treatments for individuals after QWT.

Discovering patterns in outpatient neurology appointments using state sequence analysis.

BACKGROUND: Outpatient services in the UK, and in particular outpatient neurology services, are under considerable pressure with an ever-increasing gap between capacity and demand. To improve services, we first need to understand the current situation. This study aims to explore the patterns of appointment type seen in outpatient neurology, in order to identify potential opportunities for change. METHODS: We use State Sequence Analysis (SSA) on routinely collected data from a single neurology outpatient clinic. SSA is an exploratory methodology which allows patterns within sequences of appointments to be discovered. We analyse sequences of appointments for the 18 months following a new appointment. Using SSA we create groups of similar appointment sequence patterns, and then analyse these clusters to determine if there are particular sequences common to different diagnostic categories. RESULTS: Of 1315 patients 887 patients had only one appointment. Among the 428 patients who had more than one appointment a 6 monthly cycle of appointments was apparent. SSA revealed that there were 11 distinct clusters of appointment sequence patterns. Further analysis showed that there are 3 diagnosis categories which have significant influence over which cluster a patient falls into: seizure/epilepsy, movement disorders, and headache. CONCLUSIONS: Neurology outpatient appointment sequences show great diversity, but there are some patterns which are common to specific diagnostic categories. Information about these common patterns could be used to inform the structure of future outpatient appointments.

Characterization of antipsychotic utilization before clozapine initiation for individuals with schizophrenia: an innovative visualization of trajectories using French National Health Insurance data.

AIMS: Despite recommendations to initiate clozapine after two unsuccessful trials of antipsychotics, clozapine is underprescribed and initiated too late. The aim of this study was to describe different antipsychotic treatment sequences in the 36 months before the initiation of clozapine and to characterize clusters of treatment trajectories. METHODS: Using the French National Health Insurance database, a historical cohort study of the population in an area in western France was performed. The data from all new users of clozapine with a diagnosis of schizophrenia or schizoaffective disorder in the period of 2017-2018 were evaluated. All outpatient reimbursements for antipsychotics during the 36 months before clozapine initiation were analysed. Successive reimbursements for identical treatments were grouped into treatment trials (TTs), and different trajectories were clustered using a state sequence analysis. RESULTS: The results showed 1191 TTs for 287 individuals. The mean number of TTs per individual was 3.2. Risperidone, aripiprazole and haloperidol were the main treatments delivered. The frequencies of antipsychotics used differed between monotherapies and combination therapies. A three-cluster typology was identified: one cluster (n = 133) of 'less treated' younger individuals with fewer TTs and shorter TT durations; a second cluster (n = 53) of 'more treated' individuals with higher numbers of TTs and combinations of antipsychotics; and a third cluster (n = 103) of 'treatment-stable' older individuals with longer TT durations. CONCLUSIONS: The results indicate that the median number of TTs during the 36 months before clozapine prescription was higher than the two recommended. The different trajectories were associated with individual characteristics and treatment differences, suggesting that additional studies of clinical parameters are needed to understand barriers to clozapine prescription.

Capturing the variety of clinical pathways in patients with schizophrenic disorders through state sequences analysis.

BACKGROUND: Care pathways are increasingly being used to enhance the quality of care and optimize the use of resources for health care. Nevertheless, recommendations regarding the sequence of care are mostly based on consensus-based decisions as there is a lack of evidence on effective treatment sequences. In a real-world setting, classical statistical tools were insufficient to consider a phenomenon with such high variability adequately and have to be integrated with novel data mining techniques suitable for identifying patterns in complex data structures. Data-driven techniques can potentially support empirically identifying effective care sequences by extracting them from data collected routinely. The purpose of this study is to perform a state sequence analysis (SSA) to identify different patterns of treatment and to asses whether sequence analysis may be a useful tool for profiling patients according to the treatment pattern. METHODS: The clinical application that motivated the study of this method concerns the mental health field. In fact, the care pathways of patients affected by severe mental disorders often do not correspond to the standards required by the guidelines in this field. In particular, we analyzed patients with schizophrenic disorders (i.e., schizophrenia, schizotypal or delusional disorders) using administrative data from 2015 to 2018 from Lombardy Region. This methodology considers the patient's therapeutic path as a conceptual unit, composed of a succession of different states, and we show how SSA can be used to describe longitudinal patient status. RESULTS: We define the states to be the weekly coverage of different treatments (psychiatric visits, psychosocial interventions, and anti-psychotic drugs), and we use the longest common subsequences (dis)similarity measure to compare and cluster the sequences. We obtained three different clusters with very different patterns of treatments. CONCLUSIONS: This kind of information, such as common patterns of care that allowed us to risk profile patients, can provide health policymakers an opportunity to plan optimum and individualized patient care by allocating appropriate resources, analyzing trends in the health status of a population, and finding the risk factors that can be leveraged to prevent the decline of mental health status at the population level.

Trajectories of care of community-dwelling people living with dementia: a multidimensional state sequence analysis.

BACKGROUND: The type and level of healthcare services required to address the needs of persons living with dementia fluctuate over disease progression. Thus, their trajectories of care (the sequence of healthcare use over time) may vary significantly. We aimed to (1) propose a typology of trajectories of care among community-dwelling people living with dementia; (2) describe and compare their characteristics according to their respective trajectories; and (3) evaluate the association between trajectories membership, socioeconomic factors, and self-perceived health. METHODS: This is an observational study using the data of the innovative Care Trajectories -Enriched Data (TorSaDE) cohort, a linkage between five waves of the Canadian Community Health Survey (CCHS), and health administrative data from the Quebec provincial health-insurance board. We analyzed data from 690 community-dwelling persons living with dementia who participated in at least one cycle of the CCHS (the date of the last CCHS completion is the index date). Trajectories of care were defined as sequences of healthcare use in the two years preceding the index date, using the following information: 1) Type of care units consulted (Hospitalization, Emergency department, Outpatient clinic, Primary care clinic); 2) Type of healthcare care professionals consulted (Geriatrician/psychiatrist/neurologist, Other specialists, Family physician). RESULTS: Three distinct types of trajectories describe healthcare use in persons with dementia: 1) low healthcare use (n = 377; 54.6%); 2) high primary care use (n = 154; 22.3%); 3) high overall healthcare use (n = 159; 23.0%). Group 3 membership was associated with living in urban areas, a poorer perceived health status and higher comorbidity. CONCLUSION: Further understanding how subgroups of patients use healthcare services over time could help highlight fragility areas in the allocation of care resources and implement best practices, especially in the context of resource shortage.

Trajectories of Service Contact before Suicide in People with Substance Use Disorders-A National Register Study.

OBJECTIVE: This study aimed to identify trajectories of service use during the last year before suicide death and the characteristics associated with the trajectories in patients with substance use disorders. METHODS: This study used a national registry data linkage, which included all patients with substance use disorders who died by suicide in Norway between 2010 and 2018. In- and outpatient contacts with mental health or substance use services during the last year before suicide death was analyzed by week using Sequence State Analysis and cluster analysis to identify trajectories. Logistic regression was used to measure the association between the characteristics and the trajectories. RESULTS: We identified four trajectories of service contact. A brief contact trajectory (n = 366) with a low proportion of weeks in contact (M weeks = 8.3), associated with less psychosis or bipolar disorder (aOR = 0.13 (0.08-0.22)) and higher age. A regular contact trajectory (n = 160), with a higher proportion of contact (M weeks = 47.9), associated with psychosis or bipolar disorder (aOR = 3.66 (2.10-6.47)) and depressive or anxiety disorder (aOR = 3.11 (1.93-5.13)). An intermittent contact trajectory (n = 195) with most contacts with outpatient substance use disorder services (M weeks = 9.7). A continuous contact trajectory (n = 109) with a high proportion of inpatient contact (M weeks = 44.5), strongly associated with psychosis or bipolar disorder (aOR = 6.08 (3.26-11.80)). CONCLUSION: Longitudinal descriptions of service use reveal different trajectories that are important to consider when developing policies or interventions to reduce the risk of suicide death in patients with substance use disorders.

Distinct care trajectories among persons living with arthritic conditions: A two-year state sequence analysis.

Objectives: Developing solutions to optimize care trajectories (CareTs) requires examining patient journeys through the health care system. This study aimed to describe CareTs among people living with arthritis and evaluate their association with self-reported health outcomes. Methods: Analyses were conducted using the TorSaDE Cohort (n = 102,148), which connects the 2007 to 2016 Canadian Community Health Surveys (CCHS) with Quebec administrative databases (longitudinal claims). CareTs of participants living with arthritis according to CCHS (n = 16,631), over the two years before CCHS completion, were clustered using state sequence analysis (months as a time unit). CareT group membership was then put in association with self-reported outcomes (pain intensity and interference, self-perceived general and mental health). Results: The analysis revealed five CareT groups characterized predominantly by: (1) arthritis-related visits to a specialist (n = 2,756; 16.6%), (2) arthritis-related emergency department visits (n = 2,928; 17.6%), (3) very high all-cause health care utilization and arthritis-related hospitalizations (n = 1,570; 9.4%), (4) arthritis-related medical visits to general practitioners and specialists (n = 2,708; 16.3%), (5) low all-cause health care utilization (n = 6,669; 40.1%). Multivariable results revealed that CareT group membership was associated with higher levels of pain interference (CareT group #3 vs. #5: OR: 1.4, 95%CI: 1.1-1.8) and fair/poor self-perceived general health (CareT group #1 vs. #5: OR: 1.551, 95%CI: 1.319-1.824; #2 vs. #5: OR: 1.244, 95%CI: 1.062-1.457; #3 vs. #5: OR: 1.771, 95%CI: 1.451-2.162; #4 vs. #5: OR: 1.481, 95%CI: 1.265-1.735). Discussion: Sate sequence analysis is an innovative method of studying CareTs and valuable for making evidence-based decisions taking into account inter- and intra-individual variability.

Referral trajectories in patients with vertigo, dizziness and balance disorders and their impact on health-related quality of life and functioning: results from the longitudinal multicenter study MobilE-TRA.

BACKGROUND: Due to reported barriers in the management of patients with vertigo, dizziness and balance problems (VDB), referral trajectories starting from primary care might be determined by other factors than medical necessity. The objective of this paper was to examine the impact of disease-related and other determinants on referral trajectories of older patients with VDB and to investigate, how these trajectories affect the patients' functioning and health-related quality of life (HRQoL). METHODS: Data originate from the longitudinal multicenter study MobilE-TRA, conducted in two German federal states. Referrals to neurologists or ear-nose-throat (ENT) specialists were considered. Referral patterns were visualized using a state sequence analysis. Predictors of referral trajectories were examined using a multinomial logistic regression model. Linear mixed models were calculated to assess the impact of referral patterns on the patients' HRQoL and functioning. RESULTS: We identified three patterns of referral trajectories: primary care physician (PCP) only, PCP and neurologist, and PCP and ENT. Chances of referral to a neurologist were higher for patients with a neurological comorbidity (OR = 3.22, 95%-CI [1.003; 10.327]) and lower for patients from Saxony (OR = 0.08, 95%-CI [0.013; 0.419]). Patients with a PCP and neurologist referral pattern had a lower HRQoL and lower functioning at baseline assessment. Patients with unspecific diagnoses also had lower functioning. CONCLUSION: Referral trajectories were determined by present comorbidities and the regional healthcare characteristics. Referral trajectories affected patients' HRQoL. Unspecific VDB diagnoses seem to increase the risk of ineffective management and consequently impaired functioning.

Antipsychotic utilization trajectories three years after initiating or reinitiating treatment of schizophrenia: A state sequence analysis approach.

OBJECTIVE: This study aims to describe the utilization patterns of antipsychotic (AP) medication in patients with schizophrenia (SCZ), three years after initiating or reinitiating a given AP. METHODS: Based on medico-administrative information on patients living in Quebec (Canada), this retrospective cohort study included 6444 patients with a previous diagnosis of SCZ initiating or reinitiating AP medication between January 1, 2012, and December 31, 2014, with continuous coverage by public drug insurance. For each day of follow-up (1092 days), patient was either exposed to one of the chosen categories of APs, or to none. This patient's sequence of AP exposure overtime has been referred to as the "antipsychotic utilization trajectory". These trajectories were analyzed using a State Sequence Analysis, an innovative approach which provides useful visual information on the continuation and discontinuation patterns of use over time. RESULTS: Clozapine and long-acting injectable second-generation APs had the best continuation and discontinuation patterns over 3 years among all other groups, including less switching of APs, while oral first-generation APs had the poorest patterns. These findings were comparable among incident and non-incident cohorts. Oral second-generation antipsychotics, excluding clozapine, had a poorer continuation and discontinuation pattern than long-acting injectable antipsychotics. CONCLUSION: State Sequence Analysis provides a clear representation of treatment adherence in comparison with dichotomous indicators of adherence or discontinuation. Consequently, this innovative method has shed light on the impact of the AP chosen to initiate or reinitiate treatment in SCZ, which has been identified as a key factor for long-term treatment continuation and discontinuation.

Association between previous and future antipsychotic adherence in patients initiating clozapine: real-world observational study.

BACKGROUND: Although recognised as the most effective antipsychotic for treatment-resistant schizophrenia, clozapine remains underused. One reason is the widespread concern about non-adherence to clozapine because of poor adherence before initiating clozapine. AIMS: To determine if prior poor out-patient adherence to treatmentbefore initiating clozapine predisposes to poor out-patient adherence to clozapine or to any antipsychotics (including clozapine) after its initiation. METHOD: This cohort study included 3228 patients with schizophrenia living in Quebec (Canada) initiating (with a 2-year clearance period) oral clozapine (index date) between 2009 and 2016. Using pharmacy data, out-patient adherence to treatment was measured by the medication possession ratio (MPR), over a 1-year period preceding and following the index date. Five groups of patients were formed based on their prior MPR level (independent variable). Two dependent variables were defined after clozapine initiation (good out-patient adherence to any antipsychotics and to clozapine only). Along with multiple logistic regressions, state sequence analysis was used as a visual representation of antipsychotic-use trajectories over time, before and after clozapine initiation. RESULTS: Although prior poor adherence to antipsychotics was associated with poor adherence after clozapine initiation, the absolute risk of subsequent poor adherence remained low, regardless of previous adherence level. Most patients adhered to their treatment after initiating clozapine (>68% to clozapine and >84% to any antipsychotics). CONCLUSIONS: Despite the fact that poor adherence prior to initiating clozapine is widely recognised by clinicians as a barrier for the prescription of clozapine, the current study supports the initiation of clozapine in all eligible patients.

Use of State Sequence Analysis in Pharmacoepidemiology: A Tutorial.

While state sequence analysis (SSA) has been long used in social sciences, its use in pharmacoepidemiology is still in its infancy. Indeed, this technique is relatively easy to use, and its intrinsic visual nature may help investigators to untangle the latent information within prescription data, facilitating the individuation of specific patterns and possible inappropriate use of medications. In this paper, we provide an educational primer of the most important learning concepts and methods of SSA, including measurement of dissimilarities between sequences, the application of clustering methods to identify sequence patterns, the use of complexity measures for sequence patterns, the graphical visualization of sequences, and the use of SSA in predictive models. As a worked example, we present an application of SSA to opioid prescription patterns in patients with non-cancer pain, using real-world data from Italy. We show how SSA allows the identification of patterns in prescriptions in these data that might not be evident using standard statistical approaches and how these patterns are associated with future discontinuation of opioid therapy.

Disease-modifying therapy usage in patients with multiple sclerosis in France: A 6-year population-based study.

BACKGROUND: Most data regarding the use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) comes from clinical series or regional databases that have a risk of recruitment bias. French health administrative data offers the significant advantage of being extensive in regards to both MS population coverage and DMT prescriptions. OBJECTIVES: To describe patterns of DMTs usage at the level of the entire French population of MS patients from 2010 to 2015. METHODS: MS patients were identified during a 6-year study period via the French national health data system (covering 97% of the general population) and characteristics of patients who received at least one treatment were compared to those that never received treatment over the indicated period. A state sequence analysis was performed to study in a longitudinal way MS patients who started DMTs in 2010 and then to classify them into groups of similar therapeutic patterns. DMTs were categorized into first-line, second-line and off-label use, and included untreated periods for at least six months. Groups that were obtained were described and compared using a multinomial logistic regression. RESULTS: A total of 112,415 patients with MS were identified, of whom 54.0% received at least one DMT over the 6 years. The probability of being treated significantly decreased with age. Comorbidities and physical limitations appeared to be more frequent in not treated patients than in treated patients. Significant differences were also found between the two groups regarding the use of healthcare services (hospitalizations and visits to general practitioner, neurologist and nurse). Based on the 6-year therapeutic sequences, a four-cluster typology was obtained on the 4,474 patients who started a DMT in 2010. The first group which consisted of more than half of the patients (57.0%) mainly used first-line DMTs. The second group (13.1%) represented patients with second-line DMTs whereas the third group (7.3%) was comprised of off-label users and the last group (22.6%) was composed of MS patients who received no or minimal treatments. Classification into one of these groups was associated with patient's age, long-term disease status, pregnancy occurrence, estimated level of disability, levels of care (visits to a neurologist, nurse and/or physiotherapist and hospital/rehabilitation stays) and occurrence of death. CONCLUSIONS: The exhaustive population-based dataset from the French national health data system gave the opportunity to provide a detailed description regarding the use of DMTs for MS at national level. The innovative method of state sequence analysis allowed obtaining four homogeneous groups of patients among thousands of longitudinal therapeutic sequences. The predominant place of first-line treatments was confirmed even if the type of first-line treatments has probably changed since 2015.

Change in the regulatory framework for zolpidem: What is the impact on the landscape of the prescription of sedative medications? The French national ZORRO study.

AIMS: In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency (ANSM) decreed in April 2017 the implementation of secure prescription pads. The objective of this study was to evaluate the impact of this regulatory measure on the prescription of zolpidem and other sedative medications (zopiclone, benzodiazepines and antihistamines) in long-term users of zolpidem and associated factors. METHODS: We performed a historical cohort study using data from the Generalist Sample of Beneficiaries (EGB). All patients aged over 18 years old who were long-term users (at least 3 months) before the measure were enacted. We analysed the reimbursement trajectories of zolpidem, zopiclone, benzodiazepines and antihistamines (hydroxyzine and alimemazine) up to 2 years after the measure using a state sequence analysis. RESULTS: Overall, 2502 patients were analysed. A four-cluster typology was identified: continuation of zolpidem (n = 1044, 42%), discontinuation of sedative medications (n = 766, 31%), change to zopiclone (n = 537, 21%) and change to hypnotic benzodiazepines (n = 155, 6%). The most frequently prescribed hypnotic benzodiazepine was lormetazepam. We identified age, sex, treatment for psychiatric or addictive disorder and volume of zolpidem use before the measure as factors associated with different reimbursement trajectories after the regulatory change. CONCLUSION: The regulatory change for zolpidem prescriptions reduced exposure to zolpidem among long-term users and also had a broad impact on prescriptions of other sedative medications. Switching to other medications that also present a potential risk of abuse or dependence should be carefully monitored.

Healthcare utilization after a first hospitalization for COPD: a new approach of State Sequence Analysis based on the '6W' multidimensional model of care trajectories.

BACKGROUND: Published methods to describe and visualize Care Trajectories (CTs) as patterns of healthcare use are very sparse, often incomplete, and not intuitive for non-experts. Our objectives are to propose a typology of CTs one year after a first hospitalization for Chronic Obstructive Pulmonary Disease (COPD), and describe CT types and compare patients' characteristics for each CT type. METHODS: This is an observational cohort study extracted from Quebec's medico-administrative data of patients aged 40 to 84 years hospitalized for COPD in 2013 (index date). The cohort included patients hospitalized for the first time over a 3-year period before the index date and who survived over the follow-up period. The CTs consisted of sequences of healthcare use (e.g. ED-hospital-home-GP-respiratory therapists, etc.) over a one-year period. The main variable was a CT typology, which was generated by a 'tailored' multidimensional State Sequence Analysis, based on the "6W" model of Care Trajectories. Three dimensions were considered: the care setting ("where"), the reason for consultation ("why"), and the speciality of care providers ("which"). Patients were grouped into specific CT types, which were compared in terms of care use attributes and patients' characteristics using the usual descriptive statistics. RESULTS: The 2581 patients were grouped into five distinct and homogeneous CT types: Type 1 (n = 1351, 52.3%) and Type 2 (n = 748, 29.0%) with low healthcare and moderate healthcare use respectively; Type 3 (n = 216, 8.4%) with high healthcare use, mainly for respiratory reasons, with the highest number of urgent in-hospital days, seen by pulmonologists and respiratory therapists at primary care settings; Type 4 (n = 100, 3.9%) with high healthcare use, mainly cardiovascular, high ED visits, and mostly seen by nurses in community-based primary care; Type 5 (n = 166, 6.4%) with high healthcare use, high ED visits and non-urgent hospitalisations, and with consultations at outpatient clinics and primary care settings, mainly for other reasons than respiratory or cardiovascular. Patients in the 3 highest utilization CT types were older, and had more comorbidities and more severe condition at index hospitalization. CONCLUSIONS: The proposed method allows for a better representation of the sequences of healthcare use in the real world, supporting data-driven decision making.

Use of state sequence analysis for care pathway analysis: The example of multiple sclerosis.

The concept of care pathways is increasingly being used to enhance the quality of care and to optimize the use of resources for health care. We here propose an innovative method in epidemiology that is derived from social sciences: state sequence analysis (SSA). This method takes into account the chronology of care consumption and allows for identification of specific patterns. A process for using SSA in the health area is proposed and discussed. The main steps are: data coding, measurement of dissimilarities between sequences (focusing on optimal matching methods and the choice of related costs), and application of a clustering method to obtain a typology of sequence patterns. As an example of its use in the health area, SSA was employed to analyse care pathways of a random sample of patients with multiple sclerosis. This sample has been selected from the main French healthcare database covering the period 2007 to 2013 (n = 1 000). A five-cluster typology was obtained which allowed distinction of care consumption groups. Overall, about half of the patients had low care consumption, about one quarter had medium to high consumption, and another quarter had high consumption. We conclude that state sequence analysis is an innovative and flexible methodology that is worth considering in health care research.