Comparative effect of statins on the risk of incident Alzheimer disease

ObjectiveTo investigate whether fungus-derived statins are associated with a lower risk of incident Alzheimer disease (AD) compared with synthetic statins using real-world clinical practice data.MethodsWe identified a population-based retrospective cohort of patients aged ≥60 years newly prescribed a statin between January 1, 1994, and December 31, 2012, and followed until March 31, 2015, using the UK Clinical Practice Research Datalink. Statins were consecutively classified according to their type, lipophilicity, and potency. For each group, we calculated the crude AD incidence rates per 1,000 person-years. Time-dependent Cox proportional hazards models adjusted for propensity score deciles were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) of incident AD associated with different statin categories.ResultsOver the 18-year study period, we identified 465,085 statin users, including 7,669 patients who developed AD during 2,891,268 person-years of follow-up (incidence rate 2.65 [95% CI 2.59–2.71] per 1,000 person-years). Compared to synthetic, fungus-derived statins were associated with an increased risk of AD (HR 1.09, 95% CI 1.03–1.15). Lipophilic statins also were associated with higher AD risk (HR 1.18, 95% CI 1.09–1.27) compared to hydrophilic statins, while statin potency did not modify the risk of AD (adjusted HR 1.03, 95% CI 0.98–1.08). The risk was further reduced in sensitivity analyses.ConclusionFungus-derived and lipophilic statins were not associated with decreased incidence of AD compared to synthetic and hydrophilic statins. The modest variations in the risk of incident AD observed between statin characteristics needs to be evaluated in future studies on their possible heterogeneous neuroprotective effect.

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Risk of Appendicitis among Children with Different Piped Water Supply: A Nationwide Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15081601 ◽

2018 ◽

Vol 15 (8) ◽

pp. 1601

Author(s):

Hao-Ming Li ◽

Shi-Zuo Liu ◽

Ying-Kai Huang ◽

Yuan-Chih Su ◽

Chia-Hung Kao

Keyword(s):

Water Supply ◽

Proportional Hazards ◽

Population Based ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Study Cohort ◽

Research Database ◽

Piped Water ◽

Increased Risk

Appendicitis is a common surgical condition for children. However, environmental effects, such as piped water supply, on pediatric appendicitis risk remain unclear. This longitudinal, nationwide, cohort study aimed to compare the risk of appendicitis among children with different levels of piped water supply. Using data from Taiwan Water Resource Agency and National Health Insurance Research Database, we identified 119,128 children born in 1996–2010 from areas of the lowest piped water supply (prevalence 51.21% to 63.06%) as the study cohort; additional 119,128 children of the same period in areas of the highest piped water supply (prevalence 98.97% to 99.63%) were selected as the controls. Both cohorts were propensity-score matched by baseline variables. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of appendicitis in the study cohort compared to the controls by Cox proportional hazards regression. The study cohort had a raised overall incidence rates of appendicitis compared to the control cohort (12.8 vs. 8.7 per 10,000 person-years). After covariate adjustment, the risk of appendicitis was significantly increased in the study cohort (adjusted HR = 1.46, 95% CI: 1.35, 1.58, p < 0.001). Subgroup and sensitivity analyses showed consistent results that children with low piped water supply had a higher risk of appendicitis than those with high piped water supply. This study demonstrated that children with low piped water supply were at an increased risk of appendicitis. Enhancement of piped water availability in areas lacking adequate, secure, and sanitized water supply may protect children against appendicitis.

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The risk of community-acquired pneumonia in children using gastric acid suppressants

European Respiratory Journal ◽

10.1183/13993003.03229-2020 ◽

2021 ◽

pp. 2003229

Author(s):

Linda J.T.M. van der Sande ◽

Quirijn Jöbsis ◽

Michiel A.G.E. Bannier ◽

Ewoudt M.W. van de Garde ◽

Jan J.M. Coremans ◽

...

Keyword(s):

Respiratory Disease ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Proportional Hazards ◽

Community Acquired Pneumonia ◽

Cox Proportional Hazards ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Receptor Antagonists ◽

Increased Risk

With the increased use of acid suppressants, significant potential complications, such as community-acquired pneumonia are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and community-acquired pneumonia. Our main objective was to evaluate the risk of community-acquired pneumonia in children using acid suppressants (proton pump inhibitors and/or histamine-2-receptor antagonists).We performed a cohort study using data from the Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to 4 unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of community-acquired pneumonia. The cohort consisted of 84 868 exposed and 325 329 unexposed children.Current use of proton pump inhibitors and histamine-2-receptor antagonists was associated with an increased risk of community acquired pneumonia, adjusted hazard ratio 2.05 (95% CI 1.90 to 2.22) and 1.80 (95% CI 1.67 to 1.94), respectively. The risk was even greater in patients with respiratory disease. Long term use >211 days of proton pump inhibitors and histamine-2-receptor antagonists led to a significantly greater risk of community-acquired pneumonia compared to short term use <31 days. After cessation of therapy, the risk remained increased for the following 7 months.The use of acid suppressants in children was associated with a doubled risk of community-acquired pneumonia. This risk increased with chronic use, respiratory disease and remained increased after discontinuation of therapy.

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P203 Oral glucocorticoid use is associated with hypertension in patients with RA

Rheumatology ◽

10.1093/rheumatology/keaa111.198 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Ruth E Costello ◽

Meghna Jani ◽

Belay B Yimer ◽

William G Dixon

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Incident Hypertension ◽

Increased Risk ◽

Risk Attribution ◽

Predominantly Female ◽

Oral Glucocorticoids

Abstract Background Oral glucocorticoids (GC) are frequently prescribed to patients with rheumatoid arthritis (RA), however GC use is associated with several potential side effects. Hypertension is cited as a possible side effect, but few studies have specifically investigated GC-associated hypertension in patients with RA with conflicting results. The aim of this study was to determine whether GCs were associated with an increased risk of incident hypertension in a cohort of patients with RA. Methods A retrospective cohort of patients with incident RA and no hypertension at RA diagnosis were identified from UK primary care electronic health records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use and dose, categorised as: no use, >0-4.9 mg/day, 5-7.4 mg/day, 7.5-14.9 mg/day, ≥15mg/day. A 3-month risk attribution model was used where patients continued to remain at risk for 3 months after the end of prescriptions. Hypertension was identified if a patient had either: 1) 2 consecutive systolic blood pressure (BP) measurements >140mmHg within a year, 2) 2 consecutive diastolic BP measurements >90mmHg within a year or 3) antihypertensive prescriptions on at least two occasions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards (PH) regression models were fitted to determine if there was an association between GC use and hypertension. Results There were 17,760 patients with incident RA and no hypertension. The cohort had a mean age of 56.3 ± 12.7 years and were predominantly female (68%). 7,421 (42%) were prescribed GCs during follow-up. There were 6,243 cases of incident hypertension. The Cox PH model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio: 1.17 (95% CI 1.10 to 1.24)). When categorised by dose, only doses above 7.5mg were significantly associated with hypertension (Table 1). Conclusion In this large cohort of patients with RA and without hypertension, recent GC use was associated with incident hypertension. Doses ≥7.5mg were associated with hypertension while the association with lower doses was inconclusive. Clinicians need to consider cardiovascular risk when prescribing GCs and ensure BP is regularly monitored. Disclosures R.E. Costello None. M. Jani None. B.B. Yimer None. W.G. Dixon None.

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Increased risk of trigeminal neuralgia in patients with migraine: A nationwide population-based study

Cephalalgia ◽

10.1177/0333102415623069 ◽

2016 ◽

Vol 36 (13) ◽

pp. 1218-1227 ◽

Cited By ~ 12

Author(s):

Kuan-Hsiang Lin ◽

Yung-Tai Chen ◽

Jong-Ling Fuh ◽

Shuu-Jiun Wang

Keyword(s):

Trigeminal Neuralgia ◽

Proportional Hazards ◽

Underlying Mechanism ◽

Population Based ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Research Database ◽

Increased Risk ◽

Using Data

Objectives The objectives of this article are to evaluate the association between migraine and trigeminal neuralgia and to investigate the effects of age, sex, migraine subtype, and comorbid risk factors on trigeminal neuralgia development. Methods This population-based cohort study was conducted using data from Taiwan’s National Health Insurance Research Database. Individuals aged ≥ 20 years with neurologist-diagnosed migraine between 2005 and 2009 were included. A non-headache age-, sex-, and propensity score-matched control cohort was selected for comparison. All participants were followed until the end of 2010, death, or the occurrence of trigeminal neuralgia. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for comparison of the risk of trigeminal neuralgia between groups. Results Both cohorts ( n = 137,529 each) were followed for a mean of 3.1 years. During the follow-up period, 575 patients (421,581 person-years) in the migraine cohort and 88 matched controls (438,712 person-years) were newly diagnosed with trigeminal neuralgia (incidence rates, 136.39 and 20.06/100,000 person-years, respectively). The HR for trigeminal neuralgia was 6.72 (95% CI, 5.37–8.41; p < 0.001). The association between migraine and trigeminal neuralgia remained significant in sensitivity analyses. Among migraine subtypes, patients with migraine with aura were at greater risk of trigeminal neuralgia development. No other significant interaction was identified in subgroup analyses. Conclusions Migraine is a previously unidentified risk factor for trigeminal neuralgia. The association between these conditions suggests a linked underlying mechanism, which is worthy of further exploration.

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Long-term risk of cancer following pregnancies complicated by vaginal bleeding

10.1101/2021.12.29.21268235 ◽

2022 ◽

Author(s):

Elena Dudukina ◽

Erzsébet Horváth-Puhó ◽

Henrik Toft Sørensen ◽

Vera Ehrenstein

Keyword(s):

Vaginal Bleeding ◽

Proportional Hazards ◽

Uterine Cancer ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Danish Health ◽

Increased Risk ◽

Risk Of Cancer

Objective: To investigate an association of vaginal bleeding-affected deliveries with the long-term risk of cancer as compared with vaginal bleeding-unaffected deliveries and pregnancies ending in a termination or miscarriage. Design: Registry-based cohort study in Denmark, 1995-2017. Setting: Danish health and administrative registries. Participants: Deliveries (N=37,085) affected by vaginal bleeding (VB) within 20 gestational weeks among 35,517 women, VB-unaffected deliveries (N=1,362,760) among 783,020 women, pregnancies ending in a termination (N=324,395) among 239,729 women or miscarriage (N=137,040) among 121,303 women. Main outcome measures: Incidence rates (IR) per 10,000 person-years and cumulative incidence of cancer at the end of up to 24 years of follow-up, hazard ratios (HR) with 95% confidence intervals (CIs) adjusted for age, calendar year, reproductive history, history of chronic conditions, medication use, and socioeconomic factors using Cox proportional hazards regression. Results: We observed 1,725 cancer events (IR=32.1, 95% CI: 30.6-33.6) following VB-affected deliveries, 52,620 events (IR=31.5, 95% CI: 31.2-31.7) following VB-unaffected deliveries, 12,925 events (IR=30.1, 95% CI: 29.6-30.6) following a termination and 6,080 events (IR=34.3, 95% CI: 33.4-35.1) following a miscarriage. We found no association between VB and any cancer in comparison with VB-unaffected deliveries (HR=0.98, 95% CI: 0.93-1.03), terminations (HR=1.00, 95% CI: 0.94-1.06) and miscarriages (HR=1.04, 95% CI: 0.94-1.14). Specifically, there was no increase in relative risk of breast (HR=0.94, 95% CI: 0.86-1.03), cervical (0.94, 0.77-1.14), ovarian and fallopian tube (1.16, 0.81-1.66), uterine cancer (0.78, 0.46-1.33) and other site-specific cancers across all comparisons and in sensitivity analyses. Conclusions: Having a VB-affected pregnancy ending in a delivery was not associated with an increased risk of cancer in women in comparison with having a VB-unaffected pregnancy ending in a delivery, termination or miscarriage.

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Glucocorticoid use is associated with an increased risk of hypertension

Rheumatology ◽

10.1093/rheumatology/keaa209 ◽

2020 ◽

Vol 60 (1) ◽

pp. 132-139

Author(s):

Ruth E Costello ◽

Belay B Yimer ◽

Polly Roads ◽

Meghna Jani ◽

William G Dixon

Keyword(s):

Blood Pressure ◽

Cumulative Dose ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Incident Hypertension ◽

Increased Risk

Abstract Objectives Patients with RA are frequently treated with glucocorticoids (GCs), but evidence is conflicting about whether GCs are associated with hypertension. The aim of this study was to determine whether GCs are associated with incident hypertension in patients with RA. Methods A retrospective cohort of patients with incident RA and without hypertension was identified from UK primary care electronic medical records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use, dose and cumulative dose, with a 3 month attribution window. Hypertension was identified through either: blood pressure measurements >140/90 mmHg, or antihypertensive prescriptions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards regression models were fitted to determine whether there was an association between GC use and incident hypertension. Results There were 17 760 patients in the cohort. A total of 7421 (42%) were prescribed GCs during follow-up. The incident rate of hypertension was 64.1 per 1000 person years (95% CI: 62.5, 65.7). The Cox proportional hazards model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio 1.17; 95% CI: 1.10, 1.24). When categorized by dose, only doses above 7.5 mg were significantly associated with hypertension. Cumulative dose did not indicate a clear pattern. Conclusion Recent GC use was associated with incident hypertension in patients with RA, in particular doses ≥7.5 mg were associated with hypertension. Clinicians need to consider cardiovascular risk when prescribing GCs, and ensure blood pressure is regularly monitored and treated where necessary.

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Appendectomy and Non-Typhoidal Salmonella Infection: A Population-Based Matched Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10071466 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1466

Author(s):

Den-Ko Wu ◽

Kai-Shan Yang ◽

James Cheng-Chung Wei ◽

Hei-Tung Yip ◽

Renin Chang ◽

...

Keyword(s):

Proportional Hazards ◽

International Classification Of Diseases ◽

Population Based ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Control Group ◽

Research Database ◽

Cox Proportional Hazards Models ◽

Increased Risk

The potential association between appendectomy and non-typhoidal Salmonella (NTS) infection has not been elucidated. We hypothesized that appendectomy may be associated with gut vulnerability to NTS. The data were retrospectively collected from the Taiwan National Health Insurance Research Database to describe the incidence rates of NTS infection requiring hospital admission among patients with and without an appendectomy. A total of 208,585 individuals aged ≥18 years with an appendectomy were enrolled from January 2000 to December 2012, and compared with a control group of 208,585 individuals who had never received an appendectomy matched by propensity score (1:1) by index year, age, sex, occupation, and comorbidities. An appendectomy was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification Procedure Codes. The main outcome was patients who were hospitalized for NTS. Cox proportional hazards models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Two sensitivity analyses were conducted for cross-validation. Of the 417,170 participants (215,221 (51.6%) male), 208,585 individuals (50.0%) had an appendectomy, and 112 individuals developed NTS infection requiring hospitalization. In the fully adjusted multivariable Cox proportional hazards regression model, the appendectomy group had an increased risk of NTS infection (adjusted HR (aHR), 1.61; 95% CI, 1.20–2.17). Females and individuals aged 18 to 30 years with a history of appendectomy had a statistically higher risk of NTS than the control group (aHR, 1.92; 95% CI, 1.26–2.93 and aHR, 2.67; 95% CI, 1.41–5.07). In this study, appendectomy was positively associated with subsequent hospitalization for NTS. The mechanism behind this association remains uncertain and needs further studies to clarify the interactions between appendectomy and NTS.

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AB0576 BONE EROSION IN PSORIATIC ARTHRITIS ASSOCIATED WITH PSORIASIS DURATION, SKIN, NAIL AND JOINT DISEASE SEVERITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2796 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1325.2-1326

Author(s):

M. Chamurlieva ◽

E. Loginova ◽

T. Korotaeva ◽

Y. Korsakova ◽

E. Gubar ◽

...

Keyword(s):

Clinical Practice ◽

Psoriatic Arthritis ◽

Disease Severity ◽

Bone Erosion ◽

Joint Disease ◽

Practice Research ◽

Forest Plot ◽

Clinical Practice Research Datalink ◽

Increased Risk ◽

Nail Disease

Background:Psoriatic arthritis (PsA) is heterogeneous in its clinical presentation and disease course, but many patients (pts) develop a destructive form of arthritis. Psoriasis (PsO) precedes arthritis by an average of 7 years. [1]. Theory of transition from PsO to PsA has been proposed recently [2]. But association between skin disease severity and joint disease are still unclear.Objectives:to evaluate association between bone erosion, PsO duration, skin and nail disease severity in PsA pts based on data from clinical practice (RU-PsART cohort).Methods:737 (M/F=350/387) PsA pts fulfilling the CASPAR criteria were included. Mean age 47.4±12.7 years (yrs), PsA duration 55[17;120] mos., PsO duration 165[74.5;292] mos., mean DAPSA 23.3[14;36.9] mos., HAQ-DI - 0.98 [0.5;1.38], CRP - 7.4 [2.1;18] mg/l. All pts underwent standard clinical examination (tender joins count (TJC)/68, swelling joints count (SJC)/66, CRP (mg/l), DAPSA, dactylitis, enthesitis by LEI + Plantar Facia (PF), HAQ-DI. Mild disease was defined as body surface area (BSA)≤10%, moderate to severe as BSA>10%. The presence/absent of nail PsO was evaluated. X-ray of feet and hand were done in 622 out of 737 pts. The one-factor model of logistic regression was used to identify a group of features that are associated with achievement MDA. M±SD, Me [Q25; Q75], Min-Max, %, t-test, Pierson-χ2, Manna-Whitney tests, ORs with 95% CI were performed. All p<0.05 were considered to indicate statistical significance.Results:PsO precedes of PsA by an average of 9.2 years. BSA≤10% was found in 615 out of 672 pts (91.5%), BSA>10% - in 57 out of 672 pts (8.5%). Nail PsO were seen in 230 out of 737 (31.2%). Bone erosion was found in 237 out of 622 of pts (38.1%). Among these pts nail PsO were seen in 67 out of 237 pts (28.3%). Enthesitis found in 236 out of 737 pts (42.1%), dactylitis – in 197 out 731 pts (27%), axial PsA – in 315 out of 731 pts (43.1%). Bone erosion significantly associated with PsO duration more than 5 yrs., skin and nail PsO severity, high PsA activity by DAPSA, axial manifestation and duration of PsA > 36 mos. (Figure 1).Figure 1Forest plot of factors associated with bone erosion in PsA pts.Conclusion:In our cohort the majority of PsA pts had mild PsO preceded PsA on average of 9.2 yrs. Bone erosion was found in 30% of PsA pts which associated with PsO duration, skin and nail disease severity as well as with PsA activity. Early diagnosis and therapeutic intervention within a “window of opportunity” are very important for improving outcomes and prevent structural damage in PsA.References:[1]Tillett W, et al. Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort. Rheumatol. 2017; 56, 2109–2113[2]Scher JU, et al. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol. 2019;15(3):153-166. doi: 10.1038/s41584-019-0175-0. PMID: 30742092.Disclosure of Interests:None declared.

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Development and validation of prediction models to estimate risk of primary total hip and knee replacements using data from the UK: two prospective open cohorts using the UK Clinical Practice Research Datalink

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-213894 ◽

2018 ◽

Vol 78 (1) ◽

pp. 91-99 ◽

Cited By ~ 7

Author(s):

Dahai Yu ◽

Kelvin P Jordan ◽

Kym I E Snell ◽

Richard D Riley ◽

John Bedson ◽

...

Keyword(s):

Clinical Practice ◽

Large Scale ◽

Prediction Models ◽

Cox Proportional Hazards ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Total Hip ◽

Risk Of Death ◽

Geographical Regions ◽

The Uk

ObjectivesThe ability to efficiently and accurately predict future risk of primary total hip and knee replacement (THR/TKR) in earlier stages of osteoarthritis (OA) has potentially important applications. We aimed to develop and validate two models to estimate an individual’s risk of primary THR and TKR in patients newly presenting to primary care.MethodsWe identified two cohorts of patients aged ≥40 years newly consulting hip pain/OA and knee pain/OA in the Clinical Practice Research Datalink. Candidate predictors were identified by systematic review, novel hypothesis-free ‘Record-Wide Association Study’ with replication, and panel consensus. Cox proportional hazards models accounting for competing risk of death were applied to derive risk algorithms for THR and TKR. Internal–external cross-validation (IECV) was then applied over geographical regions to validate two models.Results45 predictors for THR and 53 for TKR were identified, reviewed and selected by the panel. 301 052 and 416 030 patients newly consulting between 1992 and 2015 were identified in the hip and knee cohorts, respectively (median follow-up 6 years). The resultant model C-statistics is 0.73 (0.72, 0.73) and 0.79 (0.78, 0.79) for THR (with 20 predictors) and TKR model (with 24 predictors), respectively. The IECV C-statistics ranged between 0.70–0.74 (THR model) and 0.76–0.82 (TKR model); the IECV calibration slope ranged between 0.93–1.07 (THR model) and 0.92–1.12 (TKR model).ConclusionsTwo prediction models with good discrimination and calibration that estimate individuals’ risk of THR and TKR have been developed and validated in large-scale, nationally representative data, and are readily automated in electronic patient records.

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Epidemiology and current treatment patterns of treatment-resistant depression in Scotland: a CPRD study

BJPsych Open ◽

10.1192/bjo.2021.876 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S334-S334

Author(s):

Timothy Ming ◽

Tom Denee ◽

Gemma Scott ◽

Joachim Morrens ◽

Christopher Weatherburn

Keyword(s):

Clinical Practice ◽

Incidence Rates ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Treatment Resistant Depression ◽

Augmentation Therapy ◽

Treatment Resistant ◽

First Line ◽

Resistant Depression

AimsTo assess the incidence and treatments currently used in clinical practice for the treatment of treatment-resistant depression (TRD) in Scotland.BackgroundPatients with major depressive disorder (MDD) who have not responded to at least two successive antidepressant (AD) treatments in a single episode are described as having Treatment-Resistant Depression (TRD). Epidemiological data on TRD in Scotland is lacking. Furthermore, there is no data to our knowledge on therapies prescribed in Scottish clinical practice to treat TRD.MethodA retrospective, longitudinal cohort study was conducted using Clinical Practice Research Datalink (CPRD) medical records. Adult patients were indexed on AD prescription, requiring MDD diagnosis within 90 days, from Jan 2011-May 2018 with 360-day baseline and 180-day minimum follow-up periods. Failure of ≥2 adequate oral AD regimens following indexing constituted TRD classification. Incidence rates of MDD and TRD (within the MDD cohort) and treatment lines following TRD classification were derived.ResultThe analysis included 20,059 patients with MDD (mean age 44 years, 63% female, median follow-up 59 months); 1,374 (6.8%) were classified as TRD. Median time-to-TRD classification was 25 months. The incidence rate of MDD was 15.9 per 1,000 patient-years and for TRD was 14.7 per 1,000 MDD-patient-years. For all first four post-TRD treatment lines, SSRI monotherapy was the most commonly prescribed therapy, followed by combination (dual/triple) therapy and augmentation therapy (at least one oral AD supplemented with lithium, an antipsychotic or an anticonvulsant therapy). At first-line of TRD treatment, 1,050 (76.4%) patients received monotherapy AD, 212 (15.4%) received combination AD therapy and 112 (8.2%) received augmentation therapy. The most common monotherapy treatments at first-line TRD were sertraline (15.6%), mirtazapine (13.8%), fluoxetine (12.2%) and venlafaxine (11.6%). Among combination therapies, mirtazapine, venlafaxine, sertraline and amitriptyline were frequently used. Among the TRD and MDD cohort, no somatic treatments were coded in CPRD, although the use of these treatments was likely underestimated.ConclusionMonotherapy AD treatment was the most common therapy type for all four post-TRD treatment lines. These data support the need for new treatments that can achieve and maintain therapeutic response, and avoid continuous cycling through similar AD therapies.This study was sponsored by Janssen Cilag Ltd.

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