Nationwide Retrospective Cohort Research Articles

641 Is There Any Residual Risk of Lymphoma After Stopping Thiopurines? A Nationwide Retrospective Cohort From the Veterans’ Affairs Healthcare System

641 Is There Any Residual Risk of Lymphoma After Stopping Thiopurines? A Nationwide Retrospective Cohort From the Veterans’ Affairs Healthcare System

Treatment of Diabetes in People with Heart Failure

Treatment of Diabetes in People with Heart Failure

P468 Incidence rate of lymphoma by the cumulative duration of exposure to thiopurines: a nationwide retrospective cohort from the Veterans Affairs healthcare system

P468 Incidence rate of lymphoma by the cumulative duration of exposure to thiopurines: a nationwide retrospective cohort from the Veterans Affairs healthcare system

Steroid Saving Efficacy of Azathioprine: A Nationwide Retrospective Cohort from the Veterans Affairs Healthcare System

Purpose: The need for maintenance steroids is associated with a poor prognosis among patient with ulcerative colitis (UC). There is paucity of data regarding the efficacy of azathiopurine (AZA) in maintaining corticosteroids (CS) free remission in UC. Our aim was to assess the ability of AZA to induce CS free remission among UC patients. Methods: A retrospective cohort study was conducted using the nationwide Veterans Affairs (VA) database to identify CS dependent UC patients on AZA from October 1, 2001 to October 1, 2011 using ICD-9 codes. Patients using steroids for greater than 50% of the days in the 3 months leading up to the index AZA dose were considered as CS dependent and were included to our study. Patients were followed for 15 months after the index AZA dispense by tracking their pharmacy dispensing data for prednisone, AZA and infliximab. End points were: 1) successful remission, defined as cessation of prednisone filling activity within the study period while maintained on AZA. 2) Failure with continuance, defined as failure to be weaned off steroids while on AZA. 3) Failure with discontinuance, defined as cessation of AZA and continuation of steroids. Results: We included 548 patients (mean age 52, 92 % males, 79% Caucasian) in our analysis. At the end of 12th month of follow-up 240 (44%) UC patients had achieved successful remission, 79 (14%) failed to achieve remission with continuance of AZA, 229 (42%) failed to achieve remission with discontinuance of AZA, Figure 1. Although, 56% of the study population continued CS therapy through the end of the observation period, the average daily dose of prednisone among patients who were concomitantly taking AZA was 16 mg/day compared to 25 mg/day among those who had stopped AZA, p=0.01. Twelve patients (2%) were placed on infliximab during the follow-up period.Figure: No Caption available.Conclusion: This large nationwide UC patient cohort demonstrated that AZA was successful in attaining CS free remission in almost half of the patients. For those who did not achieve CS free status, CS daily dose was significantly reduced when comparing those who continued AZA versus those who discontinued it. When starting UC patients on steroids, AZA should be considered as a long term steroid sparing option.

Methotrexate in Ulcerative Colitis: A Nationwide Retrospective Cohort from the Veterans Affairs Healthcare System

Purpose: Methotrexate (MTX) is an immunosuppressant proven to induce remission and prevent relapse in crohn's disease but there is a paucity of data in ulcerative colitis (UC). Corticosteroids induce remission in UC but are associated with significant morbidity. The aim of this study is to describe the efficacy of MTX in achieving steroid free remission. Methods: A retrospective cohort study was conducted using the nationwide Veterans Affairs (VA) database to identify steroid dependent UC patients using MTX (oral and parenteral) from October 1, 2001 to October 1, 2011 with ICD-9 codes. Pharmacy dispensing data (dosage, initial dispense date, refill dates, and quantity) for prednisone, MTX, thiopurines, and infliximab were collected during the study period. Patients using steroids for greater than 50% of the days in the 3 months leading up to the index MTX dose were included and followed for 15 months. End points were: 1) Successful remission, defined as cessation of prednisone filling activity within the study period while continuing MTX. 2) Failure with continuance, failure to be weaned off steroids while on MTX. 3) Failure with discontinuance, cessation of MTX while continuing steroids. Results: We included 91 UC patients (mean age 59 years, male 89%, Caucasian 84%) in our analysis. The average weekly prescription dose for oral and parenteral MTX was 14 and 25 mg/week respectively. The average daily prescription dose for prednisone within the oral MTX and parenteral MTX groups was 12 and 25 mg/day respectively. The percentages of patients in the studied outcomes based upon mode of delivery of MTX are shown in Figure 1. There was a non significant trend towards dose reduction of steroids in those who were concomitantly taking oral MTX and steroids. No such trend was found in the parenteral MTX group.Figure: [1704]Conclusion: Our study represents the largest cohort of MTX and UC reported to date and suggests that approximately a third of steroid dependent UC patients were successfully weaned off steroids with MTX therapy. Prospective randomized trials are underway but in the meantime when starting patients on steroids MTX should be considered as an option in the long term management of UC patients.

Cause-specific infant mortality in a population-based Swedish study of term and post-term births: the contribution of gestational age and birth weight

ObjectiveTo investigate infant mortality and causes of infant death in relation to gestational age (GA) and birth weight for GA in non-malformed term and post-term infants.DesignObservational, retrospective nationwide cohort study.SettingSweden...

Acute Myocardial Infarction and Atherosclerosis of the Coronary Arteries in Patients Treated with Drugs Against Osteoporosis: Calcium in the Vessels and not the Bones?

We studied the association between bisphosphonate use and risk of acute myocardial infarction (AMI) or atherosclerosis of the coronary vessels using a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n=103,562) comprised the exposed group and three age- and gender-matched controls from the general population (n=310,683), the unexposed group. The main outcomes were occurrence of AMI or atherosclerosis of the coronary vessels. An excess risk of AMI was seen in users of alendronate compared to the unexposed. However, an inverse dose-response relationship was seen, with an increased risk in those with low adherence (≤0.66 DDD, HR=1.50, 95% CI 1.24-1.82) and a nonsignificantly decreased risk in those who were adherent to the drug (≥1 DDD, HR=0.80, 95% CI 0.59-1.09; P for trend <0.01). For etidronate and raloxifene, no excess risk was present and no dose-response relationship was seen. For atherosclerosis of the coronary vessels, a similar trend as for AMI was seen for alendronate but a protective effect was present at high doses (≥1 DDD, HR=0.58, 95% CI 0.49-0.70). For etidronate, an increased risk of atherosclerosis was seen at all doses, with no dose-response relationship. For raloxifene, no excess of atherosclerosis was observed. At high doses of alendronate a decreased risk of atherosclerosis of the coronary vessels was seemingly present, whereas at low doses an increased risk was present. The finding may be spurious due to the "healthy user" effect, but a causal relationship cannot be excluded.

Occurrence of Gastrointestinal Cancer in Users of Bisphosphonates and Other Antiresorptive Drugs Against Osteoporosis

We studied the association between bisphosphonate use and risk of gastrointestinal (GI) cancers in a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n=103,562) were used as the exposed group, with three age- and gender-matched controls from the general population (n=310,683) as the nonexposed group. The main outcome was occurrence of cancer of the esophagus, ventricle, small intestine, colon, pancreas, gallbladder or bile duct, or liver. Except for colon cancer, most of the GI cancers were rare. For clodronate and raloxifene, no excess risk was present for any of the GI cancers. For alendronate, an excess risk of esophageal and liver cancer was observed; however, the excess risk was most pronounced at low doses and short duration of observation. No dose-response relationship was present except for colon cancer with alendronate, where a decrease was seen with increasing dose so that at high doses a seemingly protective effect was present (≥1 defined daily dose, HR=0.29, 95% CI 0.14-0.62). For etidronate, an excess risk of esophageal, liver, pancreas, and gallbladder and bile duct cancers was seen. Again, no relationship with dose or duration of observation was present. An excess risk of esophageal and liver cancers may be seen with alendronate and etidronate. However, the association may not be causal as no dose-response or time relationship was present. For colon cancer, the decline with increasing alendronate dose may be due to a "healthy user" effect.

Risk of Atrial Fibrillation Associated with Use of Bisphosphonates and Other Drugs Against Osteoporosis: A Cohort Study

We studied the association between bisphosphonate use and risk of atrial fibrillation or flutter and the effect of confounders such as heart and lung disease in a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) were the exposed group and three age- and gender-matched controls from the general population (n = 310,683) were the nonexposed group. The main outcome measure was atrial fibrillation or atrial flutter. Before initiation of treatment against osteoporosis, no excess of atrial fibrillation or flutter was present for any drug except for etidronate (OR = 1.22, 95% CI 1.15-1.29). After initiation of treatment, raloxifene was not associated with any excess risk of atrial fibrillation (OR = 0.98, 95% CI 0.72-1.33). Etidronate (HR = 1.08, 95% CI 1.02-1.14) and alendronate (HR = 1.09, 95% CI 1.00-1.20) were associated with an excess risk of atrial fibrillation after treatment start if statistical adjustments were made for cardiovascular disease. However, this association disappeared upon statistical adjustment for chronic obstructive pulmonary disease (COPD) (etidronate HR = 1.04, 95% CI 0.98-1.10; alendronate HR = 1.05, 95% CI 0.96-1.15). In patients using etidronate (12.5% vs. 3.8%) and alendronate (11.4% vs. 4.6%) major differences were present in prevalence of COPD at start of treatment compared to matched controls. In conclusion, oral bisphosphonates do not seem to be associated with an excess risk of atrial fibrillation. Any excess risk seen in prior studies may be due to confounding from COPD.

Prognostic factors for fatal adult influenza pneumonia

To elucidate the prognostic factors for fatal adult influenza pneumonia. Complicated influenza pneumonia is a notifiable disease in Taiwan. In this retrospective nationwide cohort, medical records were reviewed in 38 qualifying cases from 2001 to 2007. In-hospital mortality was the primary endpoint of this study. The median patient age was 52 years, with the in-hospital mortality rate of 44.7%. Influenza A virus was found in 25 patients and influenza B was in 13 patients. Fifty percent of patients had no comorbidities. More than half of the patients developed sepsis, septic shock, respiratory failure or acute respiratory distress syndrome. The median duration from symptom onset to hospital visit was 3 days, and from hospital visit to death was 4 days. A univariate analysis demonstrated poor prognosis in patients with shock, respiratory rate > or =25/min, arterial pH<7.35, creatinine> or =2mg/dL and Pneumonia Severity Index IV or V. A multivariate analysis showed an association with mortality in patients with APACHE II score > or =20 (hazard ratio 5.941, p=0.024) or PaO(2)/FiO(2) ratio <150 (hazard ratio 4.194, p=0.017). Clinical knowledge of identified prognostic factors for mortality may aid management of adult influenza pneumonia.