Population-wide Cohort Study Research Articles

Quality of care for secondary cardiovascular disease prevention in 2009–2017: population-wide cohort study of antiplatelet therapy use in Scotland

BackgroundAntiplatelet therapy (APT) can substantially reduce the risk of further vascular events in individuals with established atherosclerotic cardiovascular disease (ASCVD). However, knowledge regarding the extent and determinants of APT use...

Association Between Infectious Diseases Consultation and Mortality in Hospitalized Patients With Gram-negative Bloodstream Infection: A Retrospective Population-wide Cohort Study.

Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%-76.1%, interquartile range 19.6%-41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] .77-.88, P < .0001; translating to absolute risk reduction of -3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.

Sidedness and addition of chemotherapy associated with treatment outcomes of regorafenib for metastatic colorectal cancer: a population-wide cohort study

Sidedness and addition of chemotherapy associated with treatment outcomes of regorafenib for metastatic colorectal cancer: a population-wide cohort study

Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study

ObjectivesThe utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. MethodsAdult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. ResultsThirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0–29.7%; range, 0–66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90–1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16–1.21) and fewer number of days alive and out of hospital at 30 and 90 days. DiscussionFUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.

Human lifespan and sex-specific patterns of resilience to disease: a retrospective population-wide cohort study

BackgroundSlower paces of aging are related to lower risk of developing diseases and premature death. Therefore, the greatest challenge of modern societies is to ensure that the increase in lifespan is accompanied by an increase in health span. To better understand the differences in human lifespan, new insight concerning the relationship between lifespan and the age of onset of diseases, and the ability to avoid them is needed. We aimed to comprehensively study, at a population-wide level, the sex-specific disease patterns associated with human lifespan.MethodsObservational data from the SIDIAP database of a cohort of 482,058 individuals that died in Catalonia (Spain) at ages over 50 years old between the 1st of January 2006 and the 30th of June 2022 were included. The time to the onset of the first disease in multiple organ systems, the prevalence of escapers, the percentage of life free of disease, and their relationship with lifespan were evaluated considering sex-specific traits.ResultsIn the study cohort, 50.4% of the participants were women and the mean lifespan was 83 years. The results show novel relationships between the age of onset of disease, health span, and lifespan. The key findings include: Firstly, the onset of both single and multisystem diseases is progressively delayed as lifespan increases. Secondly, the prevalence of escapers is lower in lifespans around life expectancy. Thirdly, the number of disease-free systems decreases until individuals reach lifespans around 87–88 years old, at which point it starts to increase. Furthermore, long-lived women are less susceptible to multisystem diseases. The associations between health span and lifespan are system-dependent, and disease onset and the percentage of life spent free of disease at the time of death contribute to explaining lifespan variability. Lastly, the study highlights significant system-specific disparities between women and men.ConclusionsHealth interventions focused on delaying aging and age-related diseases should be the most effective in increasing not only lifespan but also health span. The findings of this research highlight the relevance of Electronic Health Records in studying the aging process and open up new possibilities in age-related disease prevention that should assist primary care professionals in devising individualized care and treatment plans.

Longitudinal Trajectory of Opioid Prescribing and its Associated Serious Adverse Events: A Population-Wide Cohort Study in Taiwan.

Chronic opioid prescribing (COP) for noncancer pain is highly restricted in Taiwan, but tramadol is not listed in the regulation on chronic prescribing. This study investigated the trajectories of COP in noncancer pain when considering tramadol in Taiwan and identified the risk of serious adverse events. This population-wide longitudinal cohort study used the Taiwan National Health Insurance claims records from 2001 to 2016. Adults prescribed opioids (including tramadol) and without cancer were selected. Patients who received COP (opioid supply days for 28 days or continuous opioid supply for 14 days) in the first patient quarter were included, and serious adverse events were identified. Group-based trajectory models were applied to identify patients with a similar trajectory of quarterly COP. The Cox proportional hazard model was applied to assess the association between adverse events and patients' trajectories. Of the 2,360,358 noncancer opioid users, 476,934 (20.2%) received COP in the first quarter. Four groups of COP trajectory were identified, and 59,310 (12.8%) patients received COP quarterly over 2 years. Patients categorized into the trajectory of long-term COP had a significantly higher crude incidence rate of cardiovascular death, seizure, and hypoglycemia. Still, there is no newly developed opioid use disorder. There was a substantial underestimate in COP in Taiwan when tramadol was not considered. Notably, 10% of them could receive COP for over 2 years. The result raises concern about unmet pain management needs and the limited accessibility of alternative treatments for noncancer pain.

Childhood contact with social services and risk of suicide or sudden death in young adulthood: identifying hidden risk in a population-wide cohort study

BackgroundChildhood out-of-home care is associated with premature death in adulthood, in particular death by suicide, accidents and violence. However, little is known about the mortality risk in the much larger...

Use of general practitioner services among youth and young adults in Norway from 2006 to 2021

Objective To describe the frequency and content of contacts with general practitioners (GPs) among youth and young adults by sex, age and time, emphasizing mental health, sexual health and respiratory tract infections. Design Registry-based population-wide cohort study. Setting General practice in Norway 2006–2021. Subjects Norwegian residents aged 13–25 within the study period. Main outcome measures Contacts with GPs and out-of-hours services, including type of contact, specific procedures and diagnoses. Results Average number of GP consultations increased over the study period for all age groups. Conversation therapy and time-consuming consultations increased over time, while chlamydia testing and contraceptive guidance decreased among young women. Consultations with mental health diagnoses increased substantially over the study period for all age groups. Use of GP and out-of-hours services increased with age, with a peak at the end of upper secondary school. Youth more often met their own regular GP when consulting for mental health diagnoses than for respiratory tract infections. Conclusion This study confirmed the continuing trend of increasing use of general practice services among youth, with an increase in conversation therapy and consultations with mental health diagnoses. Procedures related to sexual health became less common. Youth usually meet their regular GP for consultations, in particular those whose diagnosis indicates the highest need of continuity.

Childhood contact with social services and self-harm and suicidal ideation in young adulthood: A population-wide cohort study in Northern Ireland

ObjectivesChildhood contact with social services is associated with adult suicide risk, but little is known about self-harm and suicidal ideation, which are recognised predictors of suicide. This study compares self-harm (SH) and suicidal ideation (SI) in young adults with childhood history of social services contact to unexposed peers.&#x0D; MethodA longitudinal, population-wide study of all children born 1985-1993 in Northern Ireland (NI) linking primary care registrations to social services data (1985-2015) and a national registry capturing all SH and SI presentations to the 12 Emergency Departments in NI (2012-2015). Multilevel logistic regression models estimated the association between level of contact with social services in childhood (no contact; referred but assessed as not in need (NIN); child in need (CIN); and child in care (CIC)) and SH, SI and any SH/SI, accounting for confounders and the amount of variation attributable to clustering by Health and Social Care Trust.&#x0D; ResultsThe cohort comprised 253,495 individuals (ages 18-30 years) alive and registered with a general practitioner during follow-up. Of the cohort, 4,026 presented with SH and 1,669 with SI. Individuals with a childhood history of social services contact comprised 10.8% of the cohort (2.9% NIN; 6.5% CIN; and 1.4% CIC) yet accounted for 40.9% of SH/SI cases. Likelihood of SH, SI, and any SH/SI increased stepwise with level of contact with social services. After full adjustment, young adults deemed NIN in childhood were three times more likely to present with SH/SI (OR 3.45 [95% CI 3.07-3.88]), former CIN five times more likely (OR 5.33 [95% CI 4.97-5.74]), and former CIC ten times more likely (OR 10.49 [95% CI 9.45-11.66]), relative to those with no contact.&#x0D; ConclusionAdults with a childhood history of social services contact, including those assessed as not in need, account for a disproportionate number of self-harm and suicidal ideation cases. Timely and targeted interventions aimed at this population have the potential to reduce the burden of self-harm and suicide

MOY 3 Management of acute cholecystitis in Scotland: A population wide cohort study

Abstract Aims Acute cholecystitis (AC) is a common Emergency General Surgery presentation, and is managed either by a cholecystectomy or conservatively. Surgery during the acute inflammatory phase has been shown to be safe and superior, however, operative rates vary widely. Also, medium-long term survival rates with each approach are still not definitively established. This real-world population analysis aims to describe the current management and outcomes of patients with AC across Scotland. Methods This was a national cohort study using data obtained from Information Services Division, Scotland. All adult patients with the admission diagnostic code for AC were included. Patient level data were used to identify all patients admitted to Scottish hospitals between 1997-2019 and outcomes tracked for inpatients or after discharge through the unique patient identifier. This was mapped to mortality data to establish date and cause of death. Results 47558 patients diagnosed with AC, admitted in one of 46 hospitals were included. These patients accounted for 58824 episodes (27.2% of patients encountered &amp;gt;1 episode). The study population had a median age of 58 years (IQR=43-71), 64.4% were female, and most had no comorbidities. 28741(60.4%) patients had an operative intervention during the index admission. Patients who had an operation during their index admission had a lower risk of 90-day mortality compared to non-operative management (OR 0.62, 95% CI 0.55-0.70). Conclusions In this comprehensive analysis of AC in Scotland, 60% of patients had an index cholecystectomy. Patients undergoing surgery had a superior survival to those managed conservatively, further advocating for an operative approach in this cohort.

The association between type of conception through medically assisted reproduction and childhood cognition: a Danish population-wide cohort study.

Previous research has indicated that children conceived through medically assisted reproduction (MAR) generally have cognitive outcomes comparable to or better than naturally conceived children. However, previous studies have been limited in their ability to examine this relationship at a population level and consider variations across different types of MAR. This study utilizes data from all live births in Denmark between 2006 and 2009 (n = 259 608), including a subset of births resulting from MAR conceptions (n = 13 566). The dependent variable is the standardized test scores obtained in the second and third grades of primary schools. A comparison is made between the test scores of children spontaneously conceived (SC) and those conceived through intrauterine insemination (IUI) and assisted reproductive technologies (ART). Ordinary least squares regressions are employed, with a baseline model adjusted only for birth year, as well as models that additionally account for conception-related confounders and sociodemographic family characteristics. In the baseline analysis, ART- and IUI-conceived children displayed better test scores compared with their SC peers. However, after adjusting for relevant factors, ART-conceived children performed worse than SC peers, while IUI-conceived children performed equally well as SC peers and better than ART-conceived children. These results likely reflect differences in the selection process of potential parents into the type of MAR, as well as the consequences of variations in fecundability. Nevertheless, the differences observed across conception types were overshadowed by test score disparities in socioeconomic background.

Comprehensive assessment of the management of acute cholecystitis in Scotland: population-wide cohort study.

Acute cholecystitis is one of the most common diagnoses presenting to emergency general surgery and is managed either operatively or conservatively. However, operative rates vary widely across the world. This real-world population analysis aimed to describe the current clinical management and outcomes of patients with acute cholecystitis across Scotland, UK. This was a national cohort study using data obtained from Information Services Division, Scotland. All adult patients with the admission diagnostic code for acute cholecystitis were included. Data were used to identify all patients admitted to Scottish hospitals between 1997 and 2019 and outcomes tracked for inpatients or after discharge through the unique patient identifier. This was linked to death data, including date of death. A total of 47 558 patients were diagnosed with 58 824 episodes of acute cholecystitis (with 27.2 per cent of patients experiencing more than one episode) in 46 Scottish hospitals. Median age was 58 years (interquartile range (i.q.r.) 43-71), 64.4 per cent were female, and most (76.1 per cent) had no comorbidities. A total of 28 741 (60.4 per cent) patients had an operative intervention during the index admission. Patients who had an operation during their index admission had a lower risk of 90-day mortality compared with non-operative management (OR 0.62, 95% c.i. 0.55-0.70). In this study, 60 per cent of patients had an index cholecystectomy. Patients who underwent surgery had a better survival rate compared with those managed conservatively, further advocating for an operative approach in this cohort.

Comparison of diagnoses of early-onset sepsis associated with use of Sepsis Risk Calculator versus NICE CG149: a prospective, population-wide cohort study in London, UK, 2020–2021

ObjectiveWe sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks’ gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC)...

Childhood adversity and risk of type 2 diabetes in early adulthood: results from a population-wide cohort study of 1.2 million individuals.

To examine whether childhood adversity is related to development of type 2 diabetes in early adulthood (16 to 38 years) among men and women. We used nationwide register data of 1,277,429 individuals born in Denmark between 1 January 1980 and 31 December 2001, who were still resident in Denmark and without diabetes at age 16 years. Individuals were divided into five childhood adversity groups based on their yearly exposure to childhood adversities (from age 0-15 years) across three dimensions: material deprivation, loss or threat of loss, and family dynamics. We estimated HR and hazard differences (HD) for type 2 diabetes according to the childhood adversity groups using Cox proportional hazards and Aalen additive hazards models. During follow-up from age 16 to 31 December 2018, 4860 individuals developed type 2 diabetes. Compared with the low adversity group, the risk of type 2 diabetes was higher in all other childhood adversity groups among both men and women. For example, the risk was higher in the high adversity group characterised by high rates of adversity across all three dimensions among men (HR 2.41; 95% CI 2.04, 2.85) and women (1.58; 1.31, 1.91), translating into 36.2 (25.9, 46.5) additional cases of type 2 diabetes per 100,000 person-years among men and 18.6 (8.2, 29.0) among women. Individuals who experienced childhood adversity are at higher risk of developing type 2 diabetes in early adulthood. Intervening upon proximal determinants of adversity may help reduce the number of type 2 diabetes cases among young adults.

Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study.

Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction-confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses. We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4-1) and 0.3 (0.3-0.4), respectively. Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19-vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

Sidedness and addition of chemotherapy associated with treatment outcomes of regorafenib for metastatic colorectal cancer (mCRC).

36 Background: Regorafenib is one of the options of salvage treatment for mCRC. We aimed to explore the prognostic factors of such regorafenib treatment. Methods: We searched the database of National Health Insurance, Taiwan for patients who initiated regorafenib treatment for mCRC from September 1, 2015, to December 31, 2018. Database interrogation of National Death Registry, Taiwan and Taiwan Cancer Registry was conducted for survival data and clinicopathological variables, respectively. Results: A total of 3,643 patients were included in the analysis. The median age was 61.2 years. The primary tumor was left-sided and KRAS mutant in 75.3% and 54.5% of patients, respectively; 28.9% of patients received chemotherapy simultaneously, with irinotecan as the most common companion. The median time to treatment discontinuation (TTD) was 2.3 months (95% confidence interval [CI]: 95% CI: 2.3-2.3), and the median overall survival (OS) was 7.2 months (95% CI: 6.9-7.4). Patients with left-sided primary tumors, compared with patients with right-sided tumors, exhibited significantly longer TTD (median, 2.4 vs. 2.1 months, p &lt; 0.001) and OS (median, 7.6 vs. 6.1 months, p &lt; 0.001). By contrast, TTD and OS of patients under regorafenib treatment were similar regardless the KRAS mutation status ( p = 0.415 and 0.643, respectively). Patients who received chemotherapy along with regorafenib, compared with patients who did not, also exhibited significantly longer TTD (median, 2.6 vs. 2.2 months, p &lt; 0.001) and OS (median, 8.3 vs. 6.7 months, p &lt; 0.001). In multivariate analysis adjusting age, sex, time from colorectal cancer diagnosis, hospital level, KRAS mutation, and initial regorafenib dose, left-sidedness of the primary tumor remained a predictor for better TTD (hazard ratio [HR]: 0.88, p = 0.002) and OS (HR: 0.92, p = 0.048), as well as addition of chemotherapy (for TTD, HR: 0.86, p &lt; 0.001; for OS, HR: 0.76, p &lt; 0.001). Due to the interaction between sidedness and KRAS mutation, we established separate Cox models and found that left-sided primary tumor was an independent predictor for better TTD and OS for KRAS wild-type tumors, but not for KRAS mutant tumors. Conclusions: In this population-wide cohort study, left-sided primary tumor and addition of chemotherapy were associated with better TTD and OS of regorafenib treatment for mCRC.

Patterns of enteric infections in a population-wide cohort study of sequelae, British Columbia, Canada.

We assessed patterns of enteric infections caused by 14 pathogens, in a longitudinal cohort study of sequelae in British Columbia (BC) Canada, 2005-2014. Our population cohort of 5.8 million individuals was followed for an average of 7.5 years/person; during this time, 40 523 individuals experienced 42 308 incident laboratory-confirmed, provincially reported enteric infections (96.4 incident infections per 100 000 person-years). Most individuals (38 882/40 523; 96%) had only one, but 4% had multiple concurrent infections or more than one infection across the study. Among individuals with more than one infection, the pathogens and combinations occurring most frequently per individual matched the pathogens occurring most frequently in the BC population. An additional 298 557 new fee-for-service physician visits and hospitalisations for enteric infections, that did not coincide with a reported enteric infection, also occurred, and some may be potentially unreported enteric infections. Our findings demonstrate that sequelae risk analyses should explore the possible impacts of multiple infections, and that estimating risk for individuals who may have had a potentially unreported enteric infection is warranted.

Population-wide cohort study of statin use for the secondary cardiovascular disease prevention in Scotland in 2009–2017

ObjectiveTo estimate the extent of suboptimal statin use for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD) at different stages of the treatment pathway and identify patient groups at risk...

Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales.

Background:Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear.Methods:We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history.Results:Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0–22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21–1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3–35.2) in week 1 to 1.80 (95% CI, 1.50–2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses.Conclusions:High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

364P Prevalence, treatment and survival of NTRK gene fusions in microsatellite instable metastatic colorectal cancer patients

TRK inhibitors are a treatment option for patients with NTRK fusions positive tumors, including metastatic colorectal cancer (mCRC). However, the clinical behavior, including response to standard therapy and overall survival, in NTRK fusion positive mCRC is unknown which complicates the interpretation of tumor agnostic basket trials studying TRK inhibitors. We aim to estimate the prevalence of NTRK fusions in microsatellite instable (MSI) mCRC and to determine patient characteristics and clinical behavior of this NTRK fusion subtype. FFPE tissue was requested from all MSI mCRC patients diagnosed between 2015 and 2020 in the Netherlands. Pan-Trk immunohistochemistry was used as screening method. Positive cases were analyzed by RNA-based NGS with Archer or FFPE-targeted locus capture to assess NTRK1, 2, and 3 rearrangements. Clinical data were retrieved from the Netherlands Cancer Registry. In total, 8 out of 203 tumors (3,9%) harbored an NTRK fusion: 7 rearrangements were found in the NTRK1 gene and 1 NTRK3-ETV6 fusion was detected. All NTRK-fusion positive tumors were RAS and BRAF wild-type. In the subgroup (n = 26) of RAS and BRAF wild-type MSI patients, prevalence of NTRK fusions was 23%. All NTRK-fusion positive tumors showed loss of MLH1 and PMS2 and MLH1 promotor hypermethylation was found in 7 out of 8 tumors. Benefit from chemotherapy (1/6) or anti-EGFR therapy (0/2) in NTRK-fusion positive patients was limited, but all four immunotherapy-treated patients had ongoing responses and a minimum overall survival of 470 days. The four patients who did not receive immunotherapy had a short overall survival (range 11-282 days). In this population wide cohort study, NTRK fusions are most prevalent (23%) in RAS and BRAF wild-type MSI mCRC patients. This is the first study to suggest resistance to chemotherapy and anti-EGFR therapy in NTRK-fusion positive tumors leading to impaired overall survival. In contrast, immunotherapy seems to be effective in NTRK-fusion positive patients. The clinical condition of the patient probably dictates the choice of upfront immunotherapy versus TRK inhibitors in this subgroup. We recommend early testing for NTRK fusions in RAS and BRAF wild-type MSI patients.