Weekly somapacitan had no adverse effects on glucose metabolism in adults with growth hormone deficiency.

PURPOSE: The long-term effects of long-acting growth hormone (LAGH) analogues on glucose metabolism in adult growth hormone deficiency (AGHD) are not known. We investigated the impact of LAGH somapacitan, administered once-weekly, on glucose metabolism in patients with AGHD. METHODS: In post hoc-defined analyses, we compared the effects of somapacitan with daily growth hormone (GH) and placebo on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß) in patients with AGHD across a unique data set from three phase 3 randomized controlled trials (REAL 1, REAL 2 and REAL Japan). RESULTS: No new cases of diabetes mellitus were reported with somapacitan. Among GH-naïve patients (n = 120 somapacitan, n = 119 daily GH), higher changes from baseline in FPG, HOMA-IR and fasting insulin levels were observed with daily GH versus somapacitan at 34 weeks, but not at 86 weeks. HbA1c and HOMA-ß did not differ between groups at either timepoint. Among treatment-naïve patients, sex, age, fasting insulin, glucose tolerance status and body mass index did not influence changes in glucose metabolism. In previously treated patients (REAL 1 extension: n = 51 somapacitan, n = 52 daily GH; REAL 2: n = 61 and n = 31, respectively; REAL Japan: n = 46 and n = 16, respectively), the difference in changes from baseline were not statistically significant between somapacitan and daily GH for any glucose metabolism parameters. CONCLUSIONS: Somapacitan, compared with daily GH, did not adversely affect glucose metabolism up to 86 weeks in a large cohort of treatment-naïve or previously treated patients with AGHD. Trial registrations (date of registration): NCT02229851 (2 September 2014), NCT02382939 (3 March 2015), NCT03075644 (7 March 2017).

Once-weekly Somapacitan is Effective and Well Tolerated in Adults with GH Deficiency: A Randomized Phase 3 Trial.

CONTEXT: Growth hormone (GH) replacement requires daily GH injections, which is burdensome for some adult patients with GH deficiency (AGHD). OBJECTIVE: To demonstrate efficacy and safety of somapacitan, a once-weekly reversible albumin-binding GH derivative, versus placebo in AGHD. DESIGN: Randomized, parallel-group, placebo-controlled (double-blind) and active-controlled (open-label) phase 3 trial, REAL 1 (NCT02229851). SETTING: Clinics in 17 countries. PATIENTS: Treatment-naïve patients with AGHD (n = 301 main study period, 272 extension period); 257 patients completed the trial. INTERVENTIONS: Patients were randomized 2:2:1 to once-weekly somapacitan, daily GH, or once-weekly placebo for 34 weeks (main period). During the 52-week extension period, patients continued treatment with somapacitan or daily GH. MAIN OUTCOME MEASURES: Body composition measured using dual-energy x-ray absorptiometry (DXA). The primary endpoint was change in truncal fat percentage to week 34. Insulin-like growth factor 1 (IGF-I) standard deviation score (SDS) values were used to dose titrate. RESULTS: At 34 weeks, somapacitan significantly reduced truncal fat percentage (estimated difference: -1.53% [-2.68; -0.38]; P = 0.0090), demonstrating superiority compared with placebo, and it improved other body composition parameters (including visceral fat and lean body mass) and IGF-I SDS. At 86 weeks, improvements were maintained with both somapacitan and daily GH. Somapacitan was well tolerated, with similar adverse events (including injection-site reactions) compared with daily GH. CONCLUSIONS: In AGHD patients, somapacitan administered once weekly demonstrated superiority over placebo, and the overall treatment effects and safety of somapacitan were in accordance with known effects and safety of GH replacement for up to 86 weeks of treatment. Somapacitan may provide an effective alternative to daily GH in AGHD. A short visual summary of our work is available (1).

Cancer Risk and Prognosis after a Hospital Contact for an Elevated Erythrocyte Sedimentation Rate.

BACKGROUND: An elevated erythrocyte sedimentation rate (ESR) may be a marker of occult cancer. METHODS: We linked Danish medical databases to examine cancer incidence in patients with a first-time hospital contact for elevated ESR during 1980 to 2013. We calculated standardized incidence ratios (SIR) of cancer compared with the general population, and comorbidity-adjusted HRs (aHR) versus matched population comparisons without elevated ESR. We also compared survival among patients with cancer with elevated ESR with that among patients with cancer without elevated ESR. RESULTS: During median follow-up of 4.9 years, we observed 3,926 cancers among 18,540 patients with a first-time hospital contact for elevated ESR. The risk for any cancer diagnosed during the first year following the contact for elevated ESR was 8.5% [95% confidence interval (CI), 8.1%-8.9%]. The overall 1-year cancer incidence was markedly elevated [SIR 5.3 (95% CI, 5.1-5.6); aHR 5.8 (95% CI, 5.4-6.3)] and was more than 3-fold elevated for most hematologic cancers and for cancers of the peritoneum and connective tissue in the abdominal wall, kidney, and adrenal glands. After the first year, patients were at increased risk of developing especially hematologic cancers. Patients diagnosed with cancer within 1 year after a contact for elevated ESR had poorer survival compared with matched cancer comparisons [adjusted mortality rate ratio 1.2 (95% CI, 1.1-1.3)]. CONCLUSIONS: Elevated ESR is a strong marker of undiagnosed cancer and is associated with poorer survival. IMPACT: Our findings may help clinicians in assessing absolute risk, common sites, and prognosis of cancers discovered after hospital contact with elevated ERS.

Low to Moderate Average Alcohol Consumption and Binge Drinking in Early Pregnancy: Effects on Choice Reaction Time and Information Processing Time in Five-Year-Old Children.

BACKGROUND: Deficits in information processing may be a core deficit after fetal alcohol exposure. This study was designed to investigate the possible effects of weekly low to moderate maternal alcohol consumption and binge drinking episodes in early pregnancy on choice reaction time (CRT) and information processing time (IPT) in young children. METHOD: Participants were sampled based on maternal alcohol consumption during pregnancy. At the age of 60-64 months, 1,333 children were administered a modified version of the Sternberg paradigm to assess CRT and IPT. In addition, a test of general intelligence (WPPSI-R) was administered. RESULTS: Adjusted for a wide range of potential confounders, this study showed no significant effects of average weekly maternal alcohol consumption during pregnancy on CRT or IPT. There was, however, an indication of slower CRT associated with binge drinking episodes in gestational weeks 1-4. CONCLUSION: This study observed no significant effects of average weekly maternal alcohol consumption during pregnancy on CRT or IPT as assessed by the Sternberg paradigm. However, there were some indications of CRT being associated with binge drinking during very early pregnancy. Further large-scale studies are needed to investigate effects of different patterns of maternal alcohol consumption on basic cognitive processes in offspring.

Hospital use among patients with lung cancer complicated by bone metastases and skeletal- related events: a population-based cohort study in Denmark.

OBJECTIVE: Skeletal-related events (SREs) among patients with bone metastases from lung cancer may be associated with considerable use of health care resources. We analyzed in- and outpatient hospital contacts in relation to SREs among all Danish lung cancer patients with bone metastases. METHODS: For this cohort study, we used the Danish Cancer Registry and the Danish National Registry of Patients to identify all persons diagnosed with first-time lung cancer and bone metastases from 2003 through 2009 in Denmark. We followed these patients until December 31, 2010, for the development of SREs (spinal cord compression; pathological or osteoporotic fracture, surgery to bone; or conventional external radiation therapy). We examined the number of inpatient hospitalizations, inpatient bed-days, hospital outpatient clinic visits, and emergency room visits within three time periods: a pre-SRE period (90-day period prior to the diagnostic period), a SRE diagnostic period (14-day period prior to the SRE), and a post-SRE period (90-day period after the SRE). RESULTS: We identified 1,146 patients with lung cancer, bone metastases, and ≥1 subsequent SRE among 28,443 patients with incident lung cancer. Over 75% of patients with SREs (n=852) had more than one SRE. The number of hospital bed-days was high in the post-SRE period compared to the pre-SRE period, as illustrated by patients with multiple SREs who had 10.7 (95% confidence interval, 10.4-10.9) hospital bed-days per 100 person-days in the pre-SRE period and 28.2 (95% confidence interval, 27.8-28.6) bed-days per 100 person-days in the post-SRE period. CONCLUSION: SREs secondary to bone metastases in lung cancer patients are associated with a substantial number of hospital contacts and hospital bed-days.

Evaluation of an ICD-10 algorithm to detect osteonecrosis of the jaw among cancer patients in the Danish National Registry of Patients.

PURPOSE: This study aimed to validate a predefined algorithm for osteonecrosis of the jaw (ONJ) among cancer patients in the Danish National Registry of Patients and to assess the nature of clinical information recorded in medical charts of ONJ patients. METHODS: We identified potential ONJ cases recorded in 2005-2010 among cancer patients at the hospital Departments of Oral and Maxillofacial Surgery (DOMS) in three Danish regions, using a set of codes from the International Classification of Diseases, 10th revision (ICD-10). We abstracted DOMS charts of the potential cases, had the ONJ status adjudicated by an expert ONJ adjudication committee (ONJAC), and computed positive predictive values. For patients with ONJAC-confirmed ONJ, we abstracted the charts for information on ONJ clinical course. Sensitivity of the algorithm was computed using a separate sample of 101 known ONJ cases accrued in 2005-2011. RESULTS: We identified 212 potential ONJ cases, of which 197 (93%) had charts available for abstraction. Eighty-three potential cases were confirmed by ONJAC, with a positive predictive value of 42% (95% confidence interval [CI] 35%-49%). DOMS charts of these 83 cases contained complete information on ONJ clinical course. Information about antiresorptive treatment was recorded for 84% of the patients. Among the 101 known ONJ cases, 74 had at least one prespecified ICD-10 code recorded in the Danish National Registry of Patients within ±90 days of the ONJ diagnosis (sensitivity 73%; 95%CI [64%-81%]). CONCLUSIONS: The predefined algorithm is not adequate for monitoring ONJ in pharmacovigilance studies. Additional case-finding approaches, coupled with adjudication, are necessary to estimate ONJ incidence accurately.

Survival in patients with breast cancer with bone metastasis: a Danish population-based cohort study on the prognostic impact of initial stage of disease at breast cancer diagnosis and length of the bone metastasis-free interval.

OBJECTIVES: Since population-based data on prognostic factors affecting survival in patients with breast cancer with bone metastasis (BM) are currently limited, we conducted this nationwide retrospective cohort study to examine the prognostic role of disease stage at breast cancer diagnosis and length of BM-free interval (BMFI). SETTING: Denmark. PARTICIPANTS: 2427 women with a breast cancer diagnosis between 1997 and 2011 in the Danish Cancer Registry and a concurrent or subsequent BM diagnosis in the Danish National Registry of Patients. PRIMARY AND SECONDARY OUTCOME MEASURES: Survival (crude) based on Kaplan-Meier method and mortality risk (crude and adjusted for age, year of diagnosis, estrogen receptor status and comorbidity) based on Cox proportional hazards regression analyses by stage of disease at breast cancer diagnosis and by length of BMFI (time from breast cancer to BM diagnosis), following patients from BM diagnosis until death, emigration or until 31 December 2012, whichever came first. RESULTS: Survival decreased with more advanced stage of disease at the time of breast cancer diagnosis; risk of mortality during the first year following a BM diagnosis was over two times higher for those presenting with metastatic versus localised disease (adjusted HR=2.12 (95% CI 1.71 to 2.62)). With respect to length of BMFI, survival was highest in women with a BMFI <1 year (ie, in those who presented with BM at the time of breast cancer diagnosis or were diagnosed within 1 year). However, among patients with a BMFI ≥1 year, survival increased with longer BMFI (1-year survival: 39.9% (95% CI 36.3% to 43.6%) for BMFI 1 to <3 years and 52.6% (95% CI 47.4% to 57.6%) for BMFI ≥5 years). This pattern was also observed in multivariate analyses. CONCLUSIONS: Stage of disease at breast cancer diagnosis and length of BMFI appear to be important prognostic factors for survival following BM.

The impact of chronic obstructive pulmonary disease on intensive care unit admission and 30-day mortality in patients undergoing colorectal cancer surgery: a Danish population-based cohort study.

BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) may increase the risk of postoperative complications and thus mortality after colorectal cancer (CRC) surgery, but the evidence is sparse. METHODS: We conducted this nationwide population-based cohort study in Denmark, including all patients undergoing CRC surgery in the period 2005-2011, identified through medical databases. We categorised the patients according to the history of COPD. We assessed the rate of complications within 30 days. We computed 30-day mortality among patients with/without COPD using the Kaplan-Meier method. We used Cox regression to compute HRs for death, controlling for age, gender, type of admission, cancer stage, hospital volume, alcohol-related diseases, obesity and Charlson comorbidity score. RESULTS: We identified 18 302 CRC surgery patients. Of these, 7.9% had a prior diagnosis of COPD. Among patients with COPD, 16.1% were admitted postoperatively to the intensive care unit, 1.9% were treated with mechanical ventilation, and 3.6% were treated with non-invasive ventilation. In patients without COPD, the corresponding proportions were 9.7%, 1.1% and 1.1%. The reoperation rate was 10.6% among patients with COPD and 8% among patients with cancer without COPD. 30-day mortality was 13% (95% CI 11.4% to 14.9%) among patients with COPD and 5.3% (95% CI 5.0% to 5.7%) among patients without COPD, corresponding to an adjusted HR of 1.7 (95% CI 1.5 to 2.0). CONCLUSIONS: COPD is a strong predictor for intensive care unit admission and mortality after CRC surgery.

Positive predictive value of primary inpatient discharge diagnoses of infection among cancer patients in the Danish National Registry of Patients.

PURPOSE: Pharmacovigilance studies of cancer treatment frequently monitor infections. Predictive values of algorithms identifying disease depend on prevalence of the disease in the population under study. We therefore estimated the positive predictive value (PPV) of primary inpatient diagnosis of infection among cancer patients in the Danish National Registry of Patients (DNRP). METHODS: The algorithm to identify infections in the DNPR was based on International Classification of Diseases, 10th revision (ICD-10) codes. A physician blinded to the type of sampled infection reviewed the medical charts and assessed the presence and type of infection. Using the physician global assessment as gold standard, we computed PPVs with and without requiring agreement on infection type. RESULTS: We retrieved 266 of 272 medical charts (98%). Presence of infection was confirmed in 261 patients, resulting in an overall PPV of 98% (95% confidence interval, 96%-99%). When requiring agreement on infection type, overall PPV was 77%. For skin infections, pneumonia, and sepsis, PPVs were 79%, 93% and 84%, respectively. For these infections, we additionally calculated PPVs using evidence-based criteria as the gold standard. PPV was similar for pneumonia, but lower for skin infections and sepsis. CONCLUSIONS: The Danish National Registry of Patients is suitable for monitoring infections requiring hospitalization among cancer patients.

Risk and prognosis of cancer in patients with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome may be a marker of occult cancer, but population-based studies of this association are lacking. Therefore, we examined the risk and prognosis of cancer in patients with nephrotic syndrome. METHODS: We conducted this population-based cohort study in Denmark, including all individuals diagnosed with nephrotic syndrome between 1980 and 2010 without a preceding cancer history. We computed the 5-year risk of cancer accounting for competing risk by death and standardized incidence ratios (SIRs) of cancer in patients with nephrotic syndrome relative to the general population. We compared the 5-year mortality for patients with cancer after nephrotic syndrome with that for a cancer cohort without a history of nephrotic syndrome using Cox regression adjusted for age, gender, and comorbidity. RESULTS: Of 4293 individuals with nephrotic syndrome, 338 developed an incident cancer during a median follow-up of 5.7 years. The 5-year risk of any cancer was 4.7% in patients with nephrotic syndrome, a 73% increased risk (SIR, 1.73; 95% confidence interval [CI], 1.55-1.92). The association was most pronounced for lung cancer, kidney cancer, lymphoma, and multiple myeloma. It was highest within 1 year of nephrotic syndrome diagnosis (SIR, 4.49; 95% CI, 3.68-5.42), but remained increased beyond 1 year (SIR, 1.34; 95% CI, 1.17-1.53). The 5-year mortality after cancer was 68.5% in patients with cancer with nephrotic syndrome and 63.4% in the cancer comparison cohort (adjusted hazard ratio, 1.20; 95% CI, 1.02-1.42). CONCLUSIONS: Nephrotic syndrome is a marker of occult solid tumors and hematologic malignancies and is associated with a worsened cancer prognosis.

Cancer risk among patients with congenital heart defects: a nationwide follow-up study.

OBJECTIVE: We aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population. METHODS: We identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (∼5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios. RESULTS: We identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22-2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84-1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86-2.29). CONCLUSION: The overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.

Risk of colorectal cancer in patients with acute myocardial infarction and stroke: a nationwide cohort study.

BACKGROUND: An association between colorectal cancer and acute myocardial infarction (AMI) and stroke has been suggested, but evidence is conflicting. METHOD: We conducted a population-based cohort study (1978-2010) of the association between AMI/stroke and colorectal cancer by linking nationwide Danish registries. We calculated standardized incidence ratios (SIR) of colorectal cancer after AMI/stroke as the ratios of observed to expected incidence. RESULTS: A total of 297,523 patients with AMI (median age, 69.4 years; 64% men) were followed for a median of 3.1 years (range, 0-33 years) and 4,387 developed colorectal cancer [SIR, 1.08; 95% confidence interval (CI), 1.05-1.11; P < 0.001]. In the first year of follow-up, the SIR was 1.85 (95% CI, 1.73-1.98; P < 0.001), whereas it was 0.98 (95% CI, 0.95-1.02; P = 0.318) in the second and subsequent years. We followed 246,998 patients with stroke (median age, 72.4 years; 52% men) for a median of 2.9 years (range, 0-33 years) and 3,035 developed colorectal cancer (SIR, 1.04; 95% CI, 1.00-1.07; P = 0.053). In the first year of follow-up, the SIR was 1.42 (95% CI, 1.31-1.53; P < 0.001), whereas it was 0.96 (95% CI, 0.93-1.00; P = 0.072) thereafter. We found no difference between the SIRs for ischemic and hemorrhagic stroke. The increased one-year relative risks for AMI and stroke corresponded to a 0.3% absolute risk. CONCLUSIONS: Our findings reflect detection of occult cancer at the time of the vascular event. The lack of increased risk after one year suggests that an association based on shared risk factors or chronic inflammation is unlikely. IMPACT: In patients with AMI/stroke, the diagnostic workup including screening for colorectal cancer should follow that of the general population.

Validity of an algorithm to identify osteonecrosis of the jaw in women with postmenopausal osteoporosis in the Danish National Registry of Patients.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is an adverse effect of drugs that suppress bone turnover - for example, drugs used for the treatment of postmenopausal osteoporosis. The Danish National Registry of Patients (DNRP) is potentially valuable for monitoring ONJ and its prognosis; however, no specific code for ONJ exists in the International Classification of Diseases 10th revision (ICD-10), which is currently used in Denmark. Our aim was to estimate the positive predictive value (PPV) of an algorithm to capture ONJ cases in the DNRP among women with postmenopausal osteoporosis. METHODS: We conducted this cross-sectional validation study in the Central and North Denmark Regions, with approximately 1.8 million inhabitants. In total, 54,956 women with postmenopausal osteoporosis were identified from June 1, 2005 through May 31, 2010. To identify women potentially suffering from ONJ, we applied an algorithm based on ICD-10 codes in the DNRP originating from hospital-based departments of oral and maxillofacial surgery (DOMS). ONJ was adjudicated by chart review and defined by the presence of exposed maxillofacial bone for 8 weeks or more, in the absence of recorded history of craniofacial radiation therapy. We estimated the PPV for the overall algorithm and for each separate ICD-10 code used in the algorithm. RESULTS: Charts were obtained and reviewed for all 60 women with an ICD-10 code potentially representing ONJ. Nineteen potential ONJ cases were confirmed, corresponding to an overall PPV of 32% (95% confidence interval: 20%-45%). CONCLUSION: Among women with postmenopausal osteoporosis, only about one-third of the potential ONJ cases identified by our ICD-10 based algorithm were confirmed by medical chart review, despite the restriction to patients treated at DOMS. To capture true ONJ cases among women with postmenopausal osteoporosis, alternative approaches are needed.

Hospital visits among women with skeletal-related events secondary to breast cancer and bone metastases: a nationwide population-based cohort study in Denmark.

OBJECTIVE: Skeletal-related events (SREs) among women with breast cancer may be associated with considerable use of health-care resources. We characterized inpatient and outpatient hospital visits in a national population-based cohort of Danish women with SREs secondary to breast cancer and bone metastases. METHODS: We identified first-time breast cancer patients with bone metastases from 2003 through 2009 who had a subsequent SRE (defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone). Hospital visits included the number of inpatient hospitalizations, length of stay, number of hospital outpatient clinic visits, and emergency room visits. The number of hospital visits was assessed for a pre-SRE period (90 days prior to the diagnostic period), a diagnostic period (14 days prior to the SRE), and a post-SRE period (90 days after the SRE). Patients who experienced more than one SRE during the 90-day post-SRE period were defined as having multiple SREs and were followed until 90 days after the last SRE. RESULTS: We identified 569 women with SREs secondary to breast cancer with bone metastases. The majority of women had multiple SREs (73.1%). A total of 20.9% and 33.4% of women with single and multiple SREs died in the post-SRE period, respectively. SREs were associated with a large number of hospital visits in the diagnostic period, irrespective of the number and type of SREs. Women with multiple SREs generally had a higher number of visits compared to those with a single SRE in the post-SRE period, eg, median length of hospitalization was 5 days (interquartile range 0-15) for women with a single SRE and 13 days (interquartile range 4-30) for women with multiple SREs. CONCLUSION: SREs secondary to breast cancer and bone metastases were associated with substantial use of hospital resources.

Endocarditis and risk of cancer: a Danish nationwide cohort study.

BACKGROUND: Endocarditis may be a marker for bacteremia-associated occult cancer. Intensive antibiotic treatment in endocarditis is suggested to reduce long-term cancer risk. We examined these hypotheses in a nationwide cohort study. METHODS: Endocarditis patients and cancer cases were identified from the Danish National Registry of Patients and the Danish Cancer Registry during 1978-2008. We compared the incidences of various cancers among study subjects to expected incidences based on national age-, sex-, and site-specific rates. RESULTS: We observed 997 cancers among 8445 endocarditis patients (median follow-up of 3.5 years), reflecting an increased standardized incidence rate (SIR) of 1.61 (95% confidence interval [CI], 1.51-1.71). Cancer risk was highly elevated during the first 3 months of follow-up (SIR=8.03; 95% CI, 6.92-9.26), partly due to a 15- to 30-fold increased risk of hematological or liver cancers. Between 3-month and 5-year follow-ups, cancer incidence remained 1.5-fold higher than expected, including 2- and 4-fold increased SIRs for colorectal and liver cancers, respectively. Beyond 5 years of observation, the overall cancer SIR was 1.21 (95% CI, 1.10-1.34). Long-term associations were weak for several cancers hypothesized to be associated with antibiotic use, including prostate, gastric, and breast cancer. CONCLUSION: Endocarditis is a substantial clinical marker for presence of occult cancer. We found no evidence of decreased long-term cancer risk after antibiotic treatment for endocarditis.

Lymph node enlargement and risk of haematological and solid cancer.

Enlarged lymph nodes may be a marker of occult cancer, but accurate data on cancer risk are limited. We used population-based Danish medical registries to assess cancer risk in a cohort of patients with a first-time inpatient or outpatient hospital contact for enlarged lymph nodes during 1994-2008. Observed cancer incidences were compared with that expected in the general population. We observed 1750 cancers among 11284 patients with enlarged lymph nodes during median follow up of 4.7 years. Only 389 cases were expected. Cancer risk was 11.5% [95% confidence interval (CI): 10.9-12.1%] during the first year of follow up, corresponding to an age- and sex-standardized incidence ratio (SIR) of 21.1 (95% CI: 20.0-22.3). One-year SIRs were more than 100 times increased for head and neck cancer and lymphomas. Beyond one year of follow up, overall cancer risk remained 1.4-fold (95% CI: 1.3-1.5-fold) higher than expected, while risk of lymphoma remained six to 10 times higher. Cancer risk was also elevated among patients with other conditions known to be associated with enlarged lymph nodes, such as infections and rheumatic disorders. We conclude that enlarged lymph nodes are a marker of occult cancer and long-term risk of cancer.

Thirty-day mortality after elective and emergency total colectomy in Danish patients with inflammatory bowel disease: a population-based nationwide cohort study.

OBJECTIVES: The purpose of this investigation was to assess 30-day mortality among Danish inflammatory bowel diseases (IBD) patients and to examine the prognostic impact of hospital total colectomy volume, age, gender and comorbidity. DESIGN: Cohort study. SETTING: The authors compared 30-day survival over the period 1996-2010 among 2889 IBD patients with total colectomy identified in the Danish National Registry of Patients. This registry covers all hospitals in Denmark. Postoperative survival patterns for patients with ulcerative colitis and Crohn's disease were compared, using proportional hazard regression. The regression model accounted for the timing of surgery, hospital total colectomy volume, age, gender and comorbidity. PARTICIPANTS: Patients were enrolled in the study if they had a hospital registry diagnosis of IBD, with accompanying procedure codes for total colectomy (see codes in online appendix table 1). Hospitalisations were described as elective or emergency, and patients were categorised as having Crohn's disease, ulcerative colitis or as a mixed group. OUTCOME MEASURES: Primary outcome measure was 30-day mortality. RESULTS: Among 2889 IBD patients with total colectomy, 1439 (50%) underwent surgery during an emergency hospitalisation. Thirty-day mortality was 5.3% (76/1439) among emergency cases compared with 1% (14/1450) among elective cases. The highest mortality (8.1%; 11 of 136) was observed among Crohn's patients undergoing emergency surgery. The mortality of patients with ulcerative colitis undergoing emergency surgery was 5.2% (55/1056). After elective surgery, the 30-day mortality was 0.9% (8/938) among patients with ulcerative colitis and 1.5% (3/201) among Crohn's disease patients. Low hospital total colectomy volume, comorbidity and high age were associated with increased 30-day mortality in ulcerative colitis patients undergoing emergency surgery. CONCLUSION: Emergency total colectomy among patients with ulcerative colitis and particularly Crohn's disease is associated with substantial 30-day mortality.

Chronic obstructive pulmonary disease and cancer risk: a Danish nationwide cohort study.

INTRODUCTION: Little is known about the risk of cancer in patients with chronic obstructive pulmonary disease (COPD), including which cancer sites are most affected. We examined the short- and long-term risk of lung and extrapulmonary cancer in a nationwide cohort of COPD patients. METHODS: We linked the Danish National Registry of Patients and the nationwide cancer registry, and examined the incidence of various cancers in 236,494 individuals with a first incident hospital contact with COPD during 1980-2008. The observed cancer incidence in this cohort was compared with the expected incidence in the general population on the basis of national age-, sex-, and site-specific incidence rates. RESULTS: Median follow-up was 3.5 years. During the first year of follow-up, 9434 cancers were diagnosed in COPD patients [standardized incidence ratio (SIR) = 3.1; 95% CI 3.0 to 3.2]. The 1-year SIR was 8.5 (8.2-8.9) for lung cancer, 5.1 (5.0-5.2) for all tobacco-related cancers, and 1.9 (1.9-2.0) for other cancers. In the following years, cancer incidence was increased 1.4-fold (1.4-1.5) in COPD patients. These patients had an increased risk of developing tobacco-related cancers (SIR = 2.1; 95% CI 2.0-2.1), including cancers of the lung, larynx, tongue, oral cavity, pharynx, esophagus, stomach, liver, pancreas, cervix uteri, and urinary tract (with SIRs ranging between 1.3 and 2.8). CONCLUSIONS: Patients with first-time hospital-diagnosed COPD are at considerably increased risk of developing both lung cancer and extrapulmonary cancers. Physicians should be aware of cancer in COPD patients.

Risk of cancer in patients with inflammatory bowel disease and venous thromboembolism: a nationwide cohort study.

BACKGROUND: Venous thromboembolism (VTE) may be a harbinger of cancer. Inflammatory bowel disease (IBD) is known to increase the risk of VTE, but it is unclear whether VTE in IBD patients is also a marker for occult cancer. We assessed the risk of cancer after VTE in IBD patients. METHODS: We conducted a population-based cohort study by linking Danish medical registries during 1978-2008. We calculated standardized incidence ratios (SIRs) by comparing observed cancer incidence after VTE in IBD patients with that expected based on national cancer incidence in the Danish population. RESULTS: A total of 895 IBD patients with VTE were followed for a total of 5290 person-years. During the first year of follow-up, 28 (3.1%) patients were diagnosed with cancer, corresponding to an SIR of 3.2 (95% confidence interval [CI]: 2.2, 4.7). Patients with ulcerative colitis or Crohn's disease had similar relative risks (SIR = 3.1 [95% CI: 1.9, 4.9] and SIR = 3.5 [95% CI: 1.7, 6.3], respectively). In IBD patients <55 years the SIR was 5.7 (95% CI: 2.3, 11.8) and in patients ≥55 years the SIR was 2.8 (95% CI: 1.8, 4.3). During the second and subsequent years of follow-up 61 cancers were diagnosed (SIR = 1.2 [95% CI: 0.92, 1.6]). CONCLUSIONS: In patients with IBD a VTE event is not only a consequence of their disease, but might also be a marker of occult cancer. We suggest that IBD patients with VTE should follow the same diagnostic work-up guidelines as non-IBD VTE patients.