Tomas S Bexelius

Use of Angiotensin II Receptor Blockers and the Risk of Acute Pancreatitis: A Nested Case-Control Study

Background: There is no specific treatment against acute pancreatitis (AP). A protective effect by angiotensin II receptor blockers (ARB) on AP has been suggested experimentally, but clinical evidence is scarce. Methods: We conducted a population-based case-control study using The Health Improvement Network in the United Kingdom, comprising about 167,000 hypertensive patients in the study period 1996–2005. In multivariate logistic regression analysis, odds ratios were calculated with 95% confidence intervals (CI). Adjustments included sex, age, calendar year, body mass index, tobacco smoking, alcohol, general practitioner visits per year, and various antihypertensive medications with regard to exposure to ARB, and risk of AP. Results: Among 633,281 person-years at risk, 265 new cases of AP were identified. Current users of ARB had a 37% statistically non-significant reduced risk of developing AP as compared to non-users (OR 0.63, 95% CI 0.38–1.02). No clear association was found between use of other antihypertensive drugs and risk of AP. Conclusion: Our study adds some support to previous experimental findings. Use of ARB might be associated with a reduced risk of AP. More research is needed to elucidate the potential role of ARB in the development of AP in the clinical setting.

New-onset type 2 diabetes, elevated HbA1c, anti-diabetic medications, and risk of pancreatic cancer

Background:Associations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels.Methods:A nested case–control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders.Results:Among 1 574 768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (⩾4 mmol mol−1 compared with <0 mmol mol−1) were followed by an increased OR of pancreatic cancer (OR, 2.16, 95% CI 1.72–2.72 and OR, 5.06, 95% CI 1.52–16.87, respectively). Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55–56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85–2.52), compared with no use of any anti-diabetic medications.Conclusions:New-onset type 2 diabetes and, particularly, diabetes with rising HbA1c seem to be independent risk factors for pancreatic cancer. The relation between different anti-diabetic medications and pancreatic cancer seems to vary in strength, with the highest risk among users of insulin.

Cardiovascular Disease and Risk of Acute Pancreatitis in a Population-based Study

Objectives The low-grade inflammation that characterizes cardiovascular disorders may facilitate the development of pancreatitis; therefore, we investigated the connection between cardiovascular disorders and acute pancreatitis. Methods A nested population-based case-control study was conducted in Sweden in 2006–2008. Cases had a first episode of acute pancreatitis diagnosed in the nationwide Patient Register. Controls were matched on age, sex, and calendar year and randomly selected from all Swedish residents (40–84 years old). Exposure to cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure, and stroke) was identified in the Patient Register. Relative risk of acute pancreatitis was estimated by odds ratios with 95% confidence intervals using logistic regression adjusting for confounders (matching variables, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases). Results The study included 6161 cases and 61,637 control subjects. Cardiovascular disorders were positively associated with acute pancreatitis (adjusted odds ratio, 1.35; 95% confidence interval, 1.25–1.45). Conclusions This population-based study indicates an association between cardiovascular disease and acute pancreatitis. Specifically, ischemic heart disease and hypertension seem to increase the risk of acute pancreatitis. Further research is needed to determine causality.

Increased risk of acute pancreatitis among tetracycline users in a Swedish population-based case–control study

Objective To evaluate the suggested association between tetracycline and acute pancreatitis in a large pharmacoepidemiological study. Design The use of tetracycline in relation to the risk of acute pancreatitis was examined in a nationwide case–control study of people aged 40–84 years between 2006 and 2008 in Sweden. The Swedish Patient Register was used to identify 6161 cases of first-episode acute pancreatitis. The Register of the Total Population was used to randomly select 61 637 control subjects from the general population using frequency-based density sampling, matched for age, sex, and calendar year. Tetracycline use was defined as ‘current’, ‘recent’, ‘past’ or ‘former’ if the drug had been dispensed 0–30 days, 31–180 days, 181–365 days or 1–3½ years before the index date, respectively. The risk of acute pancreatitis was estimated by unconditional logistic regression, providing ORs with 95% CIs, adjusted for potential confounding factors. Results There was a 60% increased risk of acute pancreatitis among current users of tetracycline after adjustment for potential confounders (OR=1.6, 95% CI 1.2 to 2.1). There was no increased OR for any category of previous use. Conclusion Current use of tetracycline is associated with an increased risk of acute pancreatitis, verifying previous case reports.

Selective Serotonin Reuptake Inhibitors and the Risk of Acute Pancreatitis A Swedish Population-Based Case-Control Study

Abstract Case reports have indicated an increased risk of acute pancreatitis during use of selective serotonin reuptake inhibitors (SSRIs), an association not found in a few epidemiological studies. We studied the use of SSRI in relation to risk of acute pancreatitis in a population-based case-control study of people aged 40 to 84 years between 2006 and 2008 in Sweden. The Patient Register was used to identify 6161 cases of first-episode acute pancreatitis. The Register of the Total Population was used to randomly select 61,637 control subjects from the general population using frequency-based density sampling, matched for age, sex, and calendar year. Use of SSRI was defined as “current,” “recent,” “past,” or “former” if the drug had been dispensed 1 to 114 days, 115 to 180 days, 181 to 365 days, or 1 to 3.5 years before a given index date, respectively. Logistic regression with adjustment for potential confounding factors was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). The OR for acute pancreatitis, adjusted for matching variables, was increased among present users of SSRI (OR, 1.5; 95% CI, 1.4–1.7). After adjusting for diseases or medications related to alcohol overconsumption, tobacco smoking, diabetes, ischemic heart disease, obesity, and severe pain together with educational level and marital status, the corresponding OR was 1.1 (95% CI, 1.0–1.3). After adjusting for the number of distinct medications, a proxy for comorbidity, the corresponding OR was 1.0 (95% CI, 0.9–1.1). The OR for antidepressant use other than SSRI showed a similar pattern. In conclusion, no increased risk of acute pancreatitis remained among users of SSRI after adjusting for confounding factors.

Association between personality traits and future choice of specialisation among Swedish doctors: a cross-sectional study

Background Medical students’ choice of their future specialty is influenced by several factors, including working conditions and type of patient relations. The aim of this study was to investigate the association between the choice of specialty and personality traits. Methods This is a cross-sectional questionnaire-based study of 399 alumni from Karolinska Institutet Medical School who were assumed to undergo specialty training at the time of the survey in 2013. The Big Five Inventory was used to assess the personality traits extraversion, agreeableness, conscientiousness, neuroticism and openness to experience. Medical specialties were categorised as primary care, psychiatry, internal medicine and surgical and hospital service specialties. Adjustments were made for demographic factors and the method of selection for medical school admission. Results The response rate was 72% (n=289, of which 262 were in training to become specialists). Among these, surgeons scored lower in agreeableness than physicians in primary care, internal medicine and hospital services. Psychiatrists and hospital service physicians showed lower conscientiousness compared with surgeons. Conclusions We found distinctive differences in personality traits between medical specialties even after adjusting for other potential explanatory variables. Since there are differences between specialties, for example, surgeons and psychiatrists, this supports previous findings that personality may affect medical students’ specialty choice also in a Swedish setting.

The effect of gestational age on clinical and radiological presentation of necrotizing enterocolitis

BACKGROUND/PURPOSE To test the hypothesis that clinical and radiological features of necrotizing enterocolitis vary with gestational age in all neonates with NEC and in subgroup of surgically treated patients. METHODS This was a retrospective study case series. NEC cases treated in Stockholm County from 2009 to 2014 were identified in the National Quality Register. Patients were included in the study if they had a verified NEC diagnosis and they were divided into 2 groups according to the gestational age. RESULTS A total of 89 patients were included. Of these 60 (67.4%) neonates had a gestational age <28 and 29 (32.6%) infants ≥28weeks. Surgical NEC patients were 57 (64%). Pneumatosis intestinalis at the abdominal radiographs was noted significantly more often in neonates born at ≥28weeks of gestation (86.2%) compared to extremely preterm newborns (60.0%). Neonates born at ≥28weeks of gestation presented more often bloody stools (58.6%) compared to extremely preterm newborns (20.0%). In surgical NEC patients gasless abdomen was detected in 35.6% of the neonates born <28weeks compared to 6.7% of the more mature neonates. CONCLUSIONS Extremely preterm neonates with NEC show less specific clinical and radiological signs of NEC compared to more mature neonates. This suggests that Bells classification is not adequate for the diagnosis and staging of NEC in extremely preterm neonates. LEVEL OF EVIDENCE III.

Losartan to prevent hyperenzymemia after endoscopic retrograde cholangiopan-creatography: A randomized clinical trial

AIM To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP). METHODS A triple-blind and placebo-controlled randomized clinical trial was performed at two Swedish hospitals in 2006-2008. Patients over 18 years of age undergoing ERCP, excluding those with current pancreatitis, current use of ARB, and severe disease, such as sepsis, liver and renal failure. One oral dose of 50 mg losartan or placebo was given one hour before ERCP. The relative risk of hyperenzymemia 24 h after ERCP was estimated using multivariable logistic regression, and expressed as odds ratio with 95% confidence intervals (CIs), including adjustment for potential remaining confounding. RESULTS Among 76 participating patients, 38 were randomized to the losartan and the placebo group, respectively. The incidence rates of hyperenzymemia and acute pancreatitis among all 76 participating patients were 21% and 12%, respectively. Hyperenzymemia was detected in 9 and 7 patients in the losartan and placebo group, respectively. There were no major differences between the comparison groups regarding cannulation difficulty, findings, or proportion of patients requiring drainage of the bile ducts. There were, however, more pancreatic duct injections, a greater extent of pancreatography, and more biliary sphincterotomies in the losartan group than in the placebo group. Losartan was not associated with risk of hyperenzymemia compared to the placebo group after multi-varible logistic regression analysis (odds ratio 1.6, 95%CI 0.3-7.8). CONCLUSION In this randomized trial 50 mg losartan given orally had no prophylactic effect on development of hyperenzymemia after ERCP.

Antidopaminergic drugs and acute pancreatitis : a population-based study

Objectives To evaluate the suggested association between antidopaminergic drugs and acute pancreatitis. Design A large population-based nested case–control study. Setting Swedish nationwide study from 2006 to 2008. Participants The Patient Register was used to identify 6161 cases of acute pancreatitis. The 61 637 control subjects were randomly selected from the Register of the Total Population by frequency-based density sampling, matched for age, sex and calendar year. Exposure Exposure data were extracted from the Prescribed Drug Register. Antidopaminergic drugs were grouped into antiemetic/anxiolytic and other antipsychotics. Current use of antidopaminergic drugs was defined as filling a prescription 1–114 days before index date, while previous use was 115 days to 3.5 years before index date. Main outcome measures Cases were defined as being diagnosed as having acute pancreatitis. ORs and 95% CIs were calculated using unconditional logistic regression. Results The unadjusted OR indicated an increased risk of acute pancreatitis among current users of antiemetic/anxiolytics (OR 1.9, 95% CI 1.4 to 2.6), but not in the multivariable model adjusting for alcohol-related comorbidity, chronic obstructive lung disease, ischaemic heart disease, obesity, diabetes, opioid use, gallstone disease, educational level, marital status and number of concomitant medications (OR 0.9, 95% CI 0.6 to 1.2). Similarly, among current users of other antipsychotics, the unadjusted OR was 1.4 (95% CI 1.1 to 1.6), while the adjusted OR was 0.8 (95% CI 0.6 to 0.9). Results regarding previous use of antidopaminergic drugs followed a similar risk pattern as for current use. Conclusions The lack of association between antidopaminergic drugs and acute pancreatitis after adjustment for confounding factors in this study suggests that the previously reported positive associations might be explained by confounding.

Medical students’ experiences of their own professional development during three clinical terms: a prospective follow-up study

BackgroundA modern competency-based medical education is well implemented globally, but less is known about how the included learning activities contribute to medical students’ professional development. The aim of this study was to explore Swedish medical students’ perceptions of the offered learning activities and their experiences of how these activities were connected to their professional development as defined by the CanMEDS framework.MethodsA prospective mixed method questionnaire study during three terms (internal medicine, scientific project, and surgery) in which data were collected by using contextual activity sampling system, i.e., the students were sent a questionnaire via their mobile phones every third week. All 136 medical students in the 6th of 11 terms in the autumn of 2012 were invited to participate. Seventy-four students (54%) filled in all of the required questionnaires (4 per term) for inclusion, the total number of questionnaires being 1335. The questionnaires focused on the students’ experiences of learning activities, especially in relation to the CanMEDS Roles, collaboration with others and emotions (positive, negative, optimal experiences, i.e., “flow”) related to the studies. The quantitative data was analysed statistically and, for the open-ended questions, manifest inductive content analysis was used.ResultsThree of the CanMEDs Roles, Medical Expert, Scholar, and Communicator, were most frequently reported while the four others, e.g., the role Health Advocate, were less common. Collaboration with students from other professions was most usual during the 8th term. Positive emotions and experience of “flow” were most often reported during clinical learning activities while the scientific project term was connected with more negative emotions.ConclusionsOur results showed that it is possible, even during clinical courses, to visualise the different areas of professional competence defined in the curriculum and connect these competences to the actual learning activities. Students halfway through their medical education considered the most important learning activities for their professional development to be connected with the Roles of Medical Expert, Scholar, and Communicator. Given that each of the CanMEDS Roles is at least moderately important during undergraduate medical education, the entire spectrum of the Roles should be emphasised and developed during the clinical years.