Routine primary care data for scientific research, quality of care programs and educational purposes: the Julius General Practitioners' Network (JGPN).

BACKGROUND: General Practitioners (GPs) in the Netherlands routinely register all patient contacts electronically. These records include longitudinally gathered clinical information of the patient contacts in coded data and free text. METHODS: Diagnoses are coded according to the International Coding of Primary Care (ICPC). Drug prescriptions are labelled with the Anatomical Therapeutic Chemical Classification (ATC), and letters of hospital specialists and paramedic health care professionals are linked or directly incorporated in the electronic medical files. A network of a large group of GPs collecting routine care data on an ongoing basis can be used for answering various research questions. RESULTS: The Julius General Practitioners' Network (JGPN) database consists of routine care data from over ten years of a dynamic cohort of around 370,000 individuals registered with the participating GPs from the city of Utrecht and its vicinity. Health care data are extracted anonymously every quartile of a year and these data are used by researchers. CONCLUSION: We describe the content and usability of our JGPN database, and how a wide variety of research questions could be answered, as illustrated with examples of published articles.

Economic Consequences and Potentially Preventable Costs Related to Osteoporosis in the Netherlands.

BACKGROUND: Osteoporosis often does not involve symptoms, and so the actual number of patients with osteoporosis is higher than the number of diagnosed individuals. This underdiagnosis results in a treatment gap. OBJECTIVES: To estimate the total health care resource use and costs related to osteoporosis in the Netherlands, explicitly including fractures, and to estimate the proportion of fracture costs that are linked to the treatment gap and might therefore be potentially preventable; to also formulate, on the basis of these findings, strategies to optimize osteoporosis care and treatment and reduce its related costs. METHODS: In this retrospective study, data of the Achmea Health Database representing 4.2 million Dutch inhabitants were used to investigate the economic consequence of osteoporosis in the Netherlands in 2010. Specific cohorts were created to identify osteoporosis-related fractures and their costs. Besides, costs of pharmaceutical treatment regarding osteoporosis were included. Using data from the literature, the treatment gap was estimated. Sensitivity analysis was performed on the base-case results. RESULTS: A total of 108,013 individuals with a history of fractures were included in this study. In this population, 59,193 patients were using anti-osteoporotic medication and 86,776 patients were using preventive supplements. A total number of 3,039 osteoporosis-related fractures occurred. The estimated total costs were €465 million. On the basis of data presented in the literature, the treatment gap in our study population was estimated to vary from 60% to 72%. CONCLUSIONS: The estimated total costs corrected for treatment gap were €1.15 to €1.64 billion. These results indicate room for improvement in the health care policy against osteoporosis.

Frequent Use of Antibiotics Is Associated with Colorectal Cancer Risk: Results of a Nested Case-Control Study.

BACKGROUND: Microbiotical dysbiosis induced by a Western diet seems to be associated with an increased risk of developing colorectal cancer (CRC). Few other factors with an effect on the colonic microbiota and their association with CRC have been evaluated. AIM: We investigated whether the use of antibiotics is associated with CRC risk. METHODS: Data on the use of antibiotics and comedication were extracted from a health insurance database for subjects with a diagnostic-related group for CRC between 2006 and 2011 and four age- and sex-matched controls. Antibiotic use was categorized according to the number of prescriptions during a 5-year follow-up period (1-6 years prior to CRC). Multivariable conditional binary logistic regression analysis was used to estimate odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for different levels of use. RESULTS: A total of 4029 cases (47 % male, mean age at diagnosis 71 ± 11 years) and 15,988 controls were included. Antibiotics had been prescribed to 2630 (65.3 %) cases and 10,234 (64.0 %) controls (p = 0.13). An increasing use of antibiotics was associated with an increasing risk of CRC [multivariable OR for high (≥8 prescriptions) vs. no prescriptions: 1.26, 95 % CI 1.11-1.44, p-trend <0.01]. For each increase of 5 prescriptions, the OR for CRC was 1.05 (95 % CI 1.01-1.09). CONCLUSION: We found an association between the use of antibiotics, especially when used frequently, and the risk of developing CRC. Further studies are needed to establish under which conditions the use of antibiotics increases the risk of developing CRC.

Local Geographical Distribution of Acute Involuntary Psychiatric Admissions in Subdistricts In and Around Utrecht, the Netherlands.

BACKGROUND: Acute involuntary psychiatric admissions (AIPA) tend to be applied more often in urban areas. OBJECTIVE: The current study aims to describe AIPA prevalence differences between the subdistricts in an urban area, and to identify which district characteristics are associated with a higher AIPA district density. METHODS: Information was collected on consecutive AIPAs over a 64-month period (2005-2010) in 49 subdistricts in and around the city of Utrecht, the Netherlands, including 1098 AIPAs. District characteristics included several demographic and economical factors and health care characteristics such as number of sheltered living facilities. RESULTS: The AIPA density (mean 4.4/10,000 inhabitants/y) was four to five times higher in the most urbanized subdistrict (around 12) compared to the suburban subdistricts (2.5-3). On the district level, the main correlates with AIPA density per district were unemployment rate and small household size. Other correlates were percentage of non-Western immigrants and number of facilities of sheltered living. CONCLUSIONS: The considerable AIPA density variation between subdistricts in this urban environment reflects that people who are prone to psychiatric admissions live in economically less prosperous environments. Impaired social networks and economic concerns may also contribute to an environment representing social defeat, increased demoralization, or social fragmentation.

Effectiveness of pharmacotherapy in behavioural therapeutic smoking cessation programmes.

BACKGROUND: In 2011, pharmacotherapy as a part of smoking cessation treatment was reimbursed through the basic health insurance in the Netherlands. We examine the (cost)-effectiveness of pharmacotherapy added to behavioural therapy. METHODS: An observational study was conducted using data from the suppliers of the smoking cessation programmes together with information on costs from health insurance company Achmea. National suppliers, general practitioners and healthcare centres offered four different programmes. (i) Behavioural support (=therapy); (ii) Behavioural support combined with nicotine replacement therapy (NRT); (iii) Behavioural support combined with smoking cessation aids (=medication) (SCA); (iv) Behavioural support combined with NRT and SCA. The primary independent variable was the programme type, and the primary outcome was whether someone quitted smoking. To examine the effectiveness of the different programmes logistic regression and logistic multilevel analyses were performed. Bootstrapping was used to evaluate cost-effectiveness. RESULTS: The results indicate that behavioural support combined with SCA has more quitters than the reference programme of behavioural support alone, and it also seems the most cost-effective programme for general practitioners and healthcare centres. Behavioural therapy combined with NRT had also more quitters, although the difference with the reference programme was smaller. CONCLUSION: Behavioural support combined with SCA seems the most successful programme. However, as we performed an observational study, firm conclusions about the differences in effectiveness between the programme types cannot be made. Future research should consider the type of smoker (smoking history, amount of cigarettes per day).

Neighborhood ethnic density and psychotic disorders among ethnic minority groups in Utrecht City.

PURPOSE: Recent studies have shown increased incidence of non-affective psychotic disorders (NAPD) among ethnic minorities compared to the native population, but not, or less so, in areas with a high own-group proportion. The aim is to investigate this ethnic density effect in Utrecht and whether this effect is due to higher rates of NAPD among Dutch persons in areas with high minority proportions. We also explore the geographical scale at which this effect occurs and the influence of social drift prior to NAPD. METHODS: NAPD cases in the Psychiatric Case Registry Middle Netherlands (N = 2,064) and living in Utrecht during 2000-2009 were analyzed in a Poisson model in relation to both individual-level and district- vs. neighborhood-level characteristics. RESULTS: With increasing minority density, especially of the neighborhood, the rate ratios of NAPD significantly decreased among both non-Western (from 2.36 to 1.24) and Western immigrants (from 1.63 to 1.01), in comparison with Dutch persons. This was partly explained by higher rates of NAPD among Dutch persons in areas with high minority density. But there was also a trend to lower NAPD rates among non-Western minorities in these areas (P = 0.074).This trend was significant among Surinamese/Antilleans (P = 0.001) and Moroccans aged 18-30 years (P = 0.046). Among the Dutch, a social drift to minority-dense neighborhoods prior to NAPD registration was found. CONCLUSIONS: Our findings support the beneficial association with own-group presence at the smaller scale neighborhood level. Findings show also that this association is more pronounced in immigrant vs. native comparisons and is not found within all ethnic groups.

Infection load as a predisposing factor for somatoform disorders: evidence from a Dutch General Practice Registry.

OBJECTIVE: Somatoform disorders (SDs) are characterized by chronic multiple functional somatic (FS) symptoms. It has been suggested that infections may be triggers for FS symptoms to occur, pointing to the immune system as a pathogenic factor in their development. The current study aimed to compare the prevalence of infections (i.e., infection load) in the history of patients with SDs with that of matched controls. METHODS: Samples (n = 185) were identified in the Psychiatric Case Register Middle Netherlands and the Julius General Practitioners Network. Patients with an SD diagnosis in the Psychiatric Case Register Middle Netherlands were compared with matched persons without somatoform complaints (controls) on their infection load in two periods before the date of the psychiatric diagnosis or a matched date for the controls (i.e., the total period for which data were available and a 3-year period). Infection load was defined as the total number of infections documented in the Julius General Practitioners Network. RESULTS: Patients with SD had significantly more infections than did controls in both periods (total period: mean [standard error] = 0.87 [0.10] versus 0.51 [0.06], z = -3.08, p = .002; 3-year period: 3.44 [0.47] versus 2.15 [0.50], z = -2.91, p = .004). CONCLUSIONS: Results show that patients with SD have a higher infection load preceding their diagnosis as compared with matched controls, implicating that infection load may indeed predispose for developing FS symptoms. These findings emphasize the importance of further research on immunological mechanisms in FS symptoms. Limitations of the study are discussed.

Cause-specific mortality among patients with psychosis: disentangling the effects of age and illness duration.

BACKGROUND: There is a large mortality gap between patients with a nonaffective psychotic disorder and those in the general population, is associated with both natural and nonnatural death causes. OBJECTIVE: This study aims to assess whether mortality risks vary for different causes of death according to the duration since diagnosis and age in a large sample of patients with nonaffective psychotic disorder. METHODS: Data of patients with nonaffective psychotic disorder (n = 12,580) from 3 Dutch psychiatric registers were linked to the cause of death register of Statistics Netherlands and compared with personally matched controls (n = 124,143) from the population register. Death rates were analyzed by duration since the date of the registered diagnosis of the (matched) patient and their age using a Poisson model. RESULTS: Among patients, the rates of all-cause death decreased with longer illness duration. This was explained by lower suicide rates. For example, among those between 40 and 60 years of age, the rate ratios (RR) of suicide during 2-5 and > 5 years were 0.52 and 0.46 (p = 0.002), respectively, when compared with the early years after diagnosis. Compared with controls, patients experienced higher rates of natural death causes during all stages and in all age categories, rate ratios 2.35-5.04; p < 0.001-0.025. There was no increase in these rate ratios with increasing duration or increasing age for patients when compared with controls. CONCLUSIONS: The high risk of natural death causes among patients with nonaffective psychotic disorder is already present at a comparatively young age. This suggests caution in blaming antipsychotics or the accumulating effects of adverse lifestyle factors for premature death. It is better to proactively monitor and treat somatic problems from the earliest disease stages onward.

Cancer mortality in patients with psychiatric diagnoses: a higher hazard of cancer death does not lead to a higher cumulative risk of dying from cancer.

PURPOSE: Both increased as well as decreased cancer mortality among psychiatric patients has been reported, but competing death causes were not included in the analyses. This study aims to investigate whether observed cancer mortality in patients with psychiatric disorders might be biased by competing death causes. METHOD: In this retrospective cohort study on data from the Psychiatric Case Register Middle Netherlands linked to the death register of Statistics Netherlands, the risk of cancer death among patients with schizophrenia (N = 4,590), bipolar disorder (N = 2,077), depression (N = 15,130) and their matched controls (N = 87,405) was analyzed using a competing risk model. RESULTS: Compared to controls, higher hazards of cancer death were found in patients with schizophrenia (HR = 1.61, 95 % CI 1.26-2.06), bipolar disorder (HR = 1.20, 95 % CI 0.81-1.79) and depression (HR = 1.26, 95 % CI 1.10-1.44). However, the HRs of death due to suicide and other death causes were more elevated. Consequently, among those who died, the 12-year cumulative risk of cancer death was significantly lower. CONCLUSIONS: Our analysis shows that, compared to the general population, psychiatric patients are at higher risk of dying from cancer, provided that they survive the much more elevated risks of suicide and other death causes.

Morbidity and doctor characteristics only partly explain the substantial healthcare expenditures of frequent attenders: a record linkage study between patient data and reimbursements data.

BACKGROUND: Frequently attending patients to primary care (FA) are likely to cost more in primary care than their non-frequently attending counterparts. But how much is spent on specialist care of FAs? We describe the healthcare expenditures of frequently attending patients during 1, 2 or 3 years and test the hypothesis that additional costs can be explained by FAs' combined morbidity and primary care physicians' characteristics. METHODS: Record linkage study. Pseudonymised clinical data from the medical records of 16 531 patients from 39 general practices were linked to healthcare insurer's reimbursements data. Main outcome measures were all reimbursed primary and specialist healthcare costs between 2007 and 2009. Multilevel linear regression analysis was used to quantify the effects of the different durations of frequent attendance on three-year total healthcare expenditures in primary and specialist care, while adjusting for age, sex, morbidities and for primary care physicians characteristics. Primary care physicians' characteristics were collected through administrative data and a questionnaire. RESULTS: Unadjusted mean 3-year expenditures were 5044 and 15 824 Euros for non-FAs and three-year-FAs, respectively. After adjustment for all other included confounders, costs both in primary and specialist care remained substantially higher and increased with longer duration of frequent attendance. As compared to non-FAs, adjusted mean expenditures were 1723 and 5293 Euros higher for one-year and three-year FAs, respectively. CONCLUSIONS: FAs of primary care give rise to substantial costs not only in primary, but also in specialist care that cannot be explained by their multimorbidity. Primary care physicians' working styles appear not to explain these excess costs. The mechanisms behind this excess expenditure remain to be elucidated.

Thiopurines prevent advanced colorectal neoplasia in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Previous studies have suggested a chemopreventive effect of 5-aminosalicylic acid (5-ASA) therapy in patients with inflammatory bowel disease (IBD). This effect has not been reported in IBD patients using thiopurines. We investigated the association between thiopurine or 5-ASA use and the risk of advanced neoplasia (AN), including high-grade dysplasia and colorectal cancer, in a large cohort of patients with IBD in the Netherlands. METHODS: PALGA, the nationwide network and registry of histo- and cytopathology in The Netherlands was linked to an anonymised computerised database of a Dutch health insurance company to identify patients with IBD with or without AN. Pharmaceutical data, including type and duration of medication use, were collected between January 2001 and December 2009. Cox proportional hazard regression analysis was used to calculate risk of AN in patients with and without thiopurine or 5-ASA use. RESULTS: A total of 2578 patients with IBD were included. Of these, 973 patients (38%) used 5-ASA, 314 (12%) thiopurines, 456 (18%) both 5-ASA and thiopurines and 835 (32%) none of these drugs. Twenty-eight patients (1%) developed AN during 16,289 person-years of follow-up. Of these, 11 patients (39%) had used 5-ASA, two (7%) thiopurines and one (4%) both drugs. Thiopurine use was associated with a significantly decreased risk of developing AN (adjusted HR 0.10, 95% CI 0.01 to 0.75). 5-ASA therapy also had a protective effect on developing AN, but this was not statistically significant (adjusted HR 0.56, 95% CI 0.22 to 1.40). CONCLUSION: Thiopurine use protects IBD patients against the development of AN. The effect of 5-ASA appeared to be less pronounced.

Familial clustering of schizophrenia, bipolar disorder, and major depressive disorder.

PURPOSE: To investigate familial clustering of schizophrenia, bipolar disorder, and major depressive disorder. METHODS: Combining data from a psychiatric case registry and Statistics Netherlands provided information on 4,673 affected probands and 18,692 matched population controls. RESULTS: Probands with schizophrenia had relative risks (RRs) for having a sibling with schizophrenia of 3.77 (95% confidence interval (CI): 2.60-5.46) and with bipolar disorder of 1.79 (95% CI: 0.64-4.96) as compared with a reference proband. Probands affected with bipolar disorder have an RR of 6.51 (95% CI: 2.60-16.29) for having a sibling with bipolar disorder and of 1.71 (95% CI: 0.71-4.14) for having a sibling with schizophrenia as compared with a reference proband. Probands affected with major depressive disorder also have increased risk for having a sibling with schizophrenia (RR: 2.04, 95% CI: 1.54-2.72) as compared with a reference proband, which was similar to the risk for having a sibling with major depressive disorder (RR: 1.91, 95% CI: 1.63-2.24) or bipolar disorder (RR: 2.06, 95% CI: 1.18-3.60). CONCLUSION: Our findings suggest, as previous studies have, that risk across schizophrenia and bipolar disorder is considerably lower (twofold) than within diagnostic entities, whereas for major depressive disorder risk is similar within and across diagnostic entities.

The psychiatric case register middle Netherlands.

BACKGROUND: The Psychiatric Case Register Middle Netherlands (PCR-MN) registers the mental healthcare consumption of over Dutch 760,000 inhabitants in the centre of the Netherlands. In 2010 the follow-up period was over ten years. In this paper we describe the content, aims and research potential of this case register. DESCRIPTION: All mental healthcare institutions in the middle-western part of the province of Utrecht participate in the PCR-MN case register. All in- and out-patients treated in these institutions have been included in the database from the period 2000 to 2010. Diagnosis according to DSM-IV on axis I to IV, visits to in- and out-patient clinics and basic demographics are recorded. A major advantage of this register is the possibility to link patients anonymously from the PCR-MN cohort to other databases to analyze relationships with determinants and outcomes, such as somatic healthcare consumption, mortality, and demographics, which further increases the research potential CONCLUSIONS: The PCR-MN database has a large potential for scientific research because of its size, duration of follow-up and ability to link with additional databases, and is accessible for academic researchers.

Differences in psychotropic drug prescriptions among ethnic groups in the Netherlands.

BACKGROUND: Psychotropic drug use in Europe and the USA has increased in the past 20 years. The rise in mental health-care use instigated a debate about possible differences in prevalence rates between different ethnic groups in the Netherlands, although the exact differences were unknown. The aim of this study was to determine whether these minority groups were more or less likely than the native population to receive psychotropic drugs. METHODS: A descriptive population study was conducted using the Agis Health Database, containing demographic and health-care consumption data of approximately 1.5 million inhabitants of the Netherlands. Rates of prescriptions of psychotropic drugs from 2001 to 2006 and adjusted odds ratios for psychotropic drug prescriptions among native Dutch, Turkish and Moroccan ethnic groups were calculated. These data were analysed using logistic regression, after being adjusted for age, gender and socioeconomic status. RESULTS: The mean year prevalence of psychotropic drug prescriptions from 2001 to 2006 was 14.0%. Except for a decrease in anxiolytic drugs, the prescriptions of psychotropic drugs increased from 2001 to 2006. These trends were the same for all of the ethnic groups considered. Among both the Moroccan and Turkish populations, there was a higher risk of antidepressant and antipsychotic drug prescriptions, and a pronounced lower risk of ADHD medication and lithium prescriptions compared to the native population. Among the Turkish population, the risk of anxiolytic drug prescriptions was greater than in the native population. CONCLUSIONS: Compared to the native population in the Netherlands, first- and second-generation Turkish and Moroccan immigrants had an increased risk of antidepressant and antipsychotic drug prescriptions and a decreased risk of ADHD medication and Lithium prescriptions. Further research is needed to clarify whether patients of different ethnic backgrounds with the same symptoms receive similar diagnosis and adequate treatment.

Trends and determinants of adequate gastroprotection in patients chronically using NSAIDs.

PURPOSE: To identify determinants and trends of gastroprotection in patients chronically using NSAIDs. DESIGN: retrospective cohort study. DATA SOURCE: Agis Health Database (AHD) containing annual prescription records of approximately 1.5 million patients. PATIENTS: All patients using more than 180 daily defined doses (DDD) annually, of any NSAID from 2001 to 2007. MAIN OUTCOME MEASURES: prevalence of NSAID use, adequate prescription of gastroprotective drugs (PPI, misoprostol or COX-2 inhibitor use), determinants of adequate gastroprotection. RESULTS: The percentage of patients chronically using NSAIDs rose from 7.3% of the total NSAIDs users in 2001 to 7.5% in 2007. The percentage of patients on NSAIDs receiving adequate gastroprotective medication in line with actual guidelines increased from 39.6% in 2001 to 69.9% in 2007. Age over 70, co-prescription of SSRI, coumarine and steroids and arthritis are the main clinical factors predicting adequate prescription. CONCLUSIONS: The prevalence of NSAID prescription and the risk of gastric complications is increasing steadily. Although the number of patients receiving gastroprotective medication is also increasing, over 30% of the patients at risk for GI complications were left unprotected in 2007. In order to improve protection rates in patients using NSAIDs and to decrease NSAID related hospital admissions in the future, the implementation of gastroprotection guidelines needs to be improved.

Effectiveness and costs of implementation strategies to reduce acid suppressive drug prescriptions: a systematic review.

BACKGROUND: Evaluation of evidence for the effectiveness of implementation strategies aimed at reducing prescriptions for the use of acid suppressive drugs (ASD). METHODS: A systematic review of intervention studies with a design according to research quality criteria and outcomes related to the effect of reduction of ASD medication retrieved from Medline, Embase and the Cochrane Library. Outcome measures were the strategy of intervention, quality of methodology and results of treatment to differences of ASD prescriptions and costs. RESULTS: The intervention varied from a single passive method to multiple active interactions with GPs. Reports of study quality had shortcomings on subjects of data-analysis. Not all outcomes were calculated but if so rction of prescriptions varied from 8% up to 40% and the cost effectiveness was in some cases negative and in others positive. Few studies demonstrated good effects from the interventions to reduce ASD. CONCLUSION: Poor quality of some studies is limiting the evidence for effective interventions. Also it is difficult to compare cost-effectiveness between studies. However, RCT studies demonstrate that active interventions are required to reduce ASD volume. Larger multi-intervention studies are necessary to evaluate the most successful intervention instruments.

Comparing episodes of antidepressants use with intermittent episodes of no use: A higher relative risk of suicide attempts but not of suicide at young age.

The Food and Drug Administration has issued a number of advisories regarding a possible causal link between antidepressants and suicide behaviour among young persons. We investigated the age dependency of (fatal) suicide attempts associated with antidepressants (N=232,561). By linking insurance claims with the death register of Statistics Netherlands (2002-2011), rates of (fatal) suicide attempts were estimated during antidepressant use and intermittent episodes without use. The age dependency of the relative risk of attempts and of suicide during episodes with compared with episodes without antidepressants was investigated by testing the {age × episode} interaction.The attempt rate during antidepressant use decreased with increasing age, concurrently with a decrease of the relative risk from 3.62 to 1.86 (p for interaction <0.001). This age dependency was found both at the early (<0.5 year) and at later stages after the first prescription (>5 years). No suicides were found among those aged <18 years, and no age dependency for the relative risk of suicide at ages ⩾ 18 was established (p>0.46). The association between antidepressants and suicide attempts at a young age does not necessarily point to a causal relationship, and, most importantly, did not translate to a similar age dependency for suicide.

Constipation-related direct medical costs in 16 887 patients newly diagnosed with chronic constipation.

BACKGROUND: Chronic constipation is a common condition, but the exact impact on healthcare budgets in Western Europe is poorly documented. OBJECTIVES: The aim of this study was to (a) investigate chronic constipation-related direct medical costs in patients with newly diagnosed chronic constipation and (b) study differences in costs according to natural history. PATIENTS AND METHODS: We identified 16 887 patients newly diagnosed with chronic constipation in a Dutch health insurance database (∼1.3 million patients) in 2006-2009. Individuals with chronic constipation were selected on the basis of chronic laxative use (≥90 days/year) and diagnostic related groups for chronic constipation. On the basis of the episodes of laxative use and diagnostic related groups, individuals were categorized as having persistent, episodic, and nonrecurrent disease. Unadjusted costs for laxatives and hospital care for chronic constipation and constipation-related comorbidities were assessed and compared between patients with nonrecurrent, episodic, and persistent disease. Factors associated with costs were identified using Cox regression analyses. RESULTS: The mean total chronic constipation-related direct medical costs in the first year after diagnosis were &OV0556;310±845 and consisted of laxatives (45%) and hospital care for chronic constipation (26%) as well as constipation-related comorbidities (29%). Costs were highest in patients with persistent disease (&OV0556;367±882) compared with patients with episodic (&OV0556;292±808) and nonrecurrent (&OV0556;263±613) disease (P<0.01). Male sex was associated with higher costs, whereas increasing age, diabetes, and use of opioids were associated with lower costs. CONCLUSION: Pharmacy costs and hospital care costs for chronic constipation-related comorbidities were the largest cost drivers for total constipation-related direct medical costs in patients with newly diagnosed chronic constipation. Direct medical costs differed according to patient characteristics.