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Nadia R Gadgaard,1 Katalin Veres,1 Victor W Henderson,1– 3 Alma B Pedersen1 1Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; 2Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA; 3Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USACorrespondence: Nadia R Gadgaard, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43-45, Aarhus, 8200, Denmark, Tel +45 87 16 72 12, Email nrg@clin.au.dkBackground: Frozen shoulder may be an early preclinical symptom of Parkinson’s disease (PD).Objective: To examine PD risk after frozen shoulder diagnosis and to evaluate this disorder as a possible manifestation of parkinsonism preceding the clinical recognition of PD and possible target for screening.Methods: Danish population-based medical registries were used to identify patients aged ≥ 40 years with a first-time frozen shoulder diagnosis (1995– 2016). A comparison cohort was randomly selected from the general population matched on age and sex. To address detection bias and the specificity of frozen shoulder diagnosis, we performed a sensitivity analysis, using similar matching criteria to select a cohort of patients with back pain diagnosis. The outcome was incident PD. Cumulative incidences and adjusted hazard ratios (HRs) were estimated with 95% confidence intervals (CIs).Results: We identified 37,041 individuals with frozen shoulder, 370,410 general population comparators, and 111,101 back pain comparators. The cumulative incidence of PD at 0– 22 years follow-up was 1.51% in the frozen shoulder cohort, 1.03% in the general population cohort, and 1.32% in the back pain cohort. For frozen shoulder versus general population, adjusted HRs were 1.94 (CI: 1.20– 3.13) at 0– 1 years and 1.45 (CI: 1.24– 1.70) at 0– 22 years follow-up. For frozen shoulder versus back pain, adjusted HRs were 0.89 (CI: 0.54– 1.46) and 1.01 (CI: 0.84– 1.21), respectively.Conclusion: Patients with frozen shoulder had an increased PD risk compared with the general population, although the absolute risks were low. Frozen shoulder might sometimes represent early manifestations of PD. Detection bias probably cannot account for the increased PD risk during the long-term follow-up.Keywords: adhesive capsulitis, back pain, cohort studies, frozen shoulder, Parkinson disease

Søren Korsgaard, Frederikke Schønfeldt Troelsen, Katalin Veres, Cecilia Hvitfeldt Fuglsang, Henrik Toft Sørensen Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, DenmarkCorrespondence: Søren Korsgaard, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43– 45, Aarhus N, 8200, Denmark, Tel +45 87167212, Email soren.korsgaard@clin.au.dkPurpose: In the Danish National Patient Registry (DNPR), covering all Danish hospitals and widely used in research, diseases have been recorded using International Classification of Diseases (ICD) codes, transitioning from the Eighth to the Tenth revision in 1994. Uncertainty exists regarding whether including ICD-8 codes alongside ICD-10 is needed for complete disease identification. We assessed the extent of left-truncation and left-censoring in the DNPR arising from omitting ICD-8 codes.Patients and Methods: We sampled 500,000 Danes ≥ 40 years of age in 1995, 2010, and 2018. From the DNPR, we identified cardiovascular, endocrine, gastrointestinal, neurological, pulmonary, rheumatic, and urogenital diseases as well as fractures. We obtained the number of people with a disease recorded with ICD-8 codes only (ie, the ICD-8 record would be left-truncated by not using ICD-8 codes), ICD-8 plus ICD-10 codes (ie, the ICD-8 record would be left-censored by not using ICD-8 codes), and ICD-10 codes only. For each ICD group, we calculated the proportion of people with the disease relative to the total sample (ie, 500,000 people) and the total number of people with the disease across all ICD groups.Results: Overall, the left-truncation issue decreased over the years. Relative to all people with a disease, the left-truncated proportion was for example 59% in 1995 and < 2% in 2018 for diabetes mellitus; 93% in 1995, and 54% in 2018 for appendicitis. The left-truncation issue increased with age group for most diseases. The proportion of disease records left-censored by not using ICD-8 codes was generally low but highest for chronic diseases.Conclusion: The left-truncation issue diminished over sample years, particularly for chronic diseases, yet remained rather high for selected surgical diseases. The left-truncation issue increased with age group for most diseases. Left-censoring was overall a minor issue that primarily concerned chronic diseases.Keywords: epidemiology, methodology, bias, left-truncation, left-censoring

Jens Sundbøll,1 Sandra Kruchov Thygesen,1 Katalin Veres,1 Donghua Liao,2 Jingbo Zhao,2 Hans Gregersen,3 Henrik Toft Sørensen11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2GIOME Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3GIOME, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong KongBackground: It remains unclear whether constipation is associated with cancer. We evaluated the risk of malignancies in patients with constipation requiring hospitalization.Methods: Using Danish medical registries, we calculated cumulative incidences and standardized incidence ratios (SIRs) for cancer. SIRs were computed as the observed number of gastrointestinal (GI) cancers and selected non-GI cancers in patients with constipation compared with the expected number based on national incidence rates by sex, age, and calendar year (1978–2013).Results: We identified 1,75,901 patients with constipation (59% females, median age 54 years). The cumulative incidences of GI cancers and non-GI cancers after 15 years of follow-up were 2.5% and 2.6%, respectively. During the first year of follow-up, the SIR for any GI cancer was 5.0 (95% confidence interval (CI): 4.8–5.3), driven by colon and pancreas cancers and higher for younger age groups. Beyond 1 year of follow-up, the risk declined to near unity for colorectal cancer. The risk of other GI cancers (including cancers of the esophagus, stomach, small intestine, liver, and pancreas) remained moderately increased (overall SIR =1.3, 95% CI: 1.2–1.4). Except for ovarian cancer (SIR =7.3, 95% CI: 6.3–8.4), the risk of non-GI cancers was only slightly increased during the first year of follow-up and declined to unity thereafter.Conclusions: Patients with constipation had increased short-term risk of a diagnosis of GI cancer. Beyond 1 year of follow-up, a moderately elevated risk persisted only for GI cancers other than colorectal cancer. The risk of non-GI cancers was elevated only during the first year of follow-up, particularly for ovarian cancer.Keywords: constipation, cancer, cohort study

Diana H Christensen,1 Katalin Veres,1 Anne G Ording,1 Jens Otto L Jørgensen,2 Suzanne C Cannegieter,3 Reimar W Thomsen,1 Henrik T Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands Objective: Risk of venous thromboembolism (VTE) is increased in patients with hypo/hyperthyroidism. It is unknown whether VTE may be a presenting symptom of occult cancer in these patients. Design: Nationwide population-based cohort study based on Danish medical registry data. Methods: We identified all patients diagnosed with VTE during 1978–2013 who had a previous or concurrent diagnosis of hypothyroidism (N=1481) or hyperthyroidism (N=1788). We followed them until a first-time cancer diagnosis, death, emigration, or study end, whichever came first. We calculated 1-year absolute cancer risk and standardized incidence ratios (SIRs) for cancer incidence in the study population compared with national cancer incidence in the general population. Results: During the first year after a VTE diagnosis, the 1-year absolute cancer risk was 3.0% among patients with hypothyroidism and 3.9% among those with hyperthyroidism. During the first year of follow-up, SIRs for cancer in the study population compared with the general population were 1.96 (95% CI: 1.42–2.64) among patients with hypothyroidism and 2.67 (95% CI: 2.07–3.39) among those with hyperthyroidism. SIRs declined substantially after 1 year but remained increased during the remainder of the follow-up period (up to 36 years) (SIR for hypothyroidism=1.16 [95% CI: 0.97–1.39]; SIR for hyperthyroidism=1.26 [95% CI: 1.08–1.46]). Conclusion: VTE may be a marker of underlying occult cancer in patients with hypothyroidism or hyperthyroidism. Keywords: hyperthyroidism, hypothyroidism, venous thromboembolism, cancer, cohort study