National Population-based Cohort Study Research Articles

Clinical Outcomes of Cardiogenic Shock due to Spontaneous Coronary Artery Dissection versus Cardiogenic Shock due to Coronary Artery Disease.

Spontaneous coronary artery dissection (SCAD) can be treated conservatively. However, some SCAD patients can develop cardiogenic shock (CS). We evaluated the outcomes of SCAD-related CS using data from a national population-based cohort study from January 1, 2016, to December 30, 2019. In our study of 32,640 patients with SCAD, about 10.6% of patients presented with cardiogenic shock. We found that SCAD patients with cardiogenic shock had higher mortality as well as greater complications including use of mechanical circulatory devices, arrythmias, respiratory support, and acute heart failure compared to those without cardiogenic shock. When comparing cardiogenic shock due to SCAD with that due to coronary artery disease (CAD), we found that while mortality rates were similar, those with cardiogenic shock due to SCAD were associated with higher risk of use of mechanical circulatory support, major bleeding, blood transfusion and respiratory failure.

Exploring the Link between Head and Neck Cancer and Elevated Risk of Rheumatoid Arthritis: A National Population-Based Cohort Study.

An increased risk of cancer among patients with rheumatoid arthritis (RA) has been reported. However, the risk of RA events among patients with head and neck cancer (HNC) is unknown. Therefore, we investigated the incidence and risk of RA among patients with HNC. This study was based on a cohort dataset. Overall, 2824 individuals without HNC and 706 patients with HNC were selected using propensity score matching. The overall RA event rate was 12.19 for patients with HNC and 7.60 for those without HNC. A significantly increased risk of developing RA was also observed among patients with HNC. The risk of developing RA over time was relatively high within the first year after HNC diagnosis; further, it increased significantly during the follow-up period. Moreover, middle-aged male patients with HNC exhibited an increased risk of developing RA compared with the controls; however, no significant difference was noted among female patients or other age groups. Notably, subgroup analysis according to cancer subtype revealed that only oral cancer survivors had an increased risk of developing RA. These results underscore the importance of vigilant monitoring by clinicians to promptly identify the onset of RA in patients with HNC.

Association of Osteoporosis-related Healthcare Costs with the Use of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide in Chronic Hepatitis B Patients: a Population-based National Cohort Study in Korea

Long-term administration of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) may lead to bone mineral density loss. Tenofovir alafenamide (TAF) developed to address these concerns. This study aimed to investigate whether there is a significant difference in osteoporosis-related healthcare costs between CHB patients treated with TDF and TAF. This study is a retrospective cohort study using claims data from the Health Insurance Review and Assessment Service (HIRA) covering the entire population in Korea. The cohort included CHB patients treated with TDF or TAF from November 2017 to April 2022. We applied inverse probability of treatment weighting (IPTW) to balance baseline characteristics observed for one-year preceding prescription date. Osteoporosis-related costs per patient per year (PPPY) included all healthcare costs with an osteoporosis diagnosis code including outpatient and hospitalization costs. 7,172 and 3,837 patients were administered TDF and TAF respectively. After IPTW, TDF group had higher outpatient costs ($11.2) compared to TAF group ($6.1), but the difference was not statistically significant (p=0.1001). The total hospitalization cost was $24.6 in TDF group and $9.8 in TAF group, not statistically significant (p=0.1633). This largescale population-based study found no significant difference in osteoporosis-related healthcare costs between CHB patients treated with TDF and TAF.

Impact of obesity on renal function in elderly Korean adults: a national population-based cohort study.

Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001). In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Predictors and Significance of Readmission after Esophagogastric Surgery: A Nationwide Analysis.

The aim of this study is to identify risk factors for readmission after elective esophagogastric cancer surgery and characterize the impact of readmission on long-term survival. The study will also identify whether the location of readmission to either the hospital that performed the primary surgery (index hospital) or another institution (nonindex hospital) has an impact on postoperative mortality. Over the past decade, the center-volume relationship has driven the centralization of major cancer surgery, which has led to improvements in perioperative mortality. However, the impact of readmission, especially to nonindex centers, on long-term mortality remains unclear. This was a national population-based cohort study using Hospital Episode Statistics of adult patients undergoing esophagectomy and gastrectomy in England between January 2008 and December 2019. This study included 27,592 patients, of which overall readmission rates were 25.1% (index 15.3% and nonindex 9.8%). The primary cause of readmission to an index hospital was surgical in 45.2% and 23.7% in nonindex readmissions. Patients with no readmissions had significantly longer survival than those with readmissions (median: 4.5 vs 3.8 years; P < 0.001). Patients readmitted to their index hospital had significantly improved survival as compared to nonindex readmissions (median: 3.3 vs 4.7 years; P < 0.001). Minimally invasive surgery and surgery performed in high-volume centers had improved 90-day mortality (odds ratio, 0.75; P < 0.001; odds ratio, 0.60; P < 0.001). Patients requiring readmission to the hospital after surgery have an increased risk of mortality, which is worsened by readmission to a nonindex institution. Patients requiring readmission to the hospital should be assessed and admitted, if required, to their index institution.

P1094 Rectal cancer in patients with inflammatory bowel disease - a nationwide cohort study

Abstract Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. The aim of this study was to investigate surgical outcome and survival in patients with rectal cancer (RC) with and without IBD. Methods The study was performed as a national population-based cohort study based on the Colorectal Cancer Data Base (CRCBaSe). All patients ≥18 years of age with a diagnosis of stage I-III RC treated with curative intent during the period 1997-2021 were included, with preliminary data for 1997-2016 available. Overall and disease-free survival after surgery was compared between patients with and without a previous diagnosis of IBD. Adjusted flexible parametric survival models were used to estimate proportional and time-dependent hazard ratios (HRs) with 95% confidence intervals (CIs). Updated data until 2021 with addition of cause-specific survival and perioperative data will be made clear by the time of the ECCO congress. Results In all, 16,263 patients with RC were included in the study, 1997-2016, among whom 235 had IBD. Patients with IBD were significantly younger, had a higher CCI, and lower tumours at diagnosis of RC, compared with patients without IBD. Among IBD patients, 45 (19.2%) were previously operated with colectomy, and 14 of these were reconstructed with ileorectal anastomosis. Among IBD patients, pT4 tumours were more prevalent (8.9%) than in patients without IBD (5.1%). Clear resection margins were less common in patients with IBD (90.6%) versus patients without IBD (95.1%). From preliminary adjusted analyses allowing the relative mortality rate to vary over follow-up time, RC patients with IBD experienced worse progression-free survival during the second year after surgery, after which their progression-free survival was superior in comparison with IBD-free patients. Conclusion The prognosis in RC patients with and without IBD varied over time. RC patients with IBD had an inferior progression-free survival initially, followed by an improved prognosis for the majority of the follow-up time. Despite a higher rate of pT4 tumours, R1-resections and lower tumors among IBD patients, unadjusted overall survival did not differ significantly compared to non-IBD CRC patients.

Community perinatal mental health teams and associations with perinatal mental health and obstetric and neonatal outcomes in pregnant women with a history of secondary mental health care in England: a national population-based cohort study

Women with a pre-existing severe mental disorder have an increased risk of relapse after giving birth. We aimed to evaluate associations of the gradual regional implementation of community perinatal mental health teams in England from April, 2016, with access to mental health care and with mental health, obstetric, and neonatal outcomes. For this cohort study, we used the national dataset of secondary mental health care provided by National Health Service England, including mental health-care episodes from April 1, 2006, to March 31, 2019, linked at patient level to the Hospital Episode Statistics, and birth notifications from the Personal Demographic Service. We included women (aged ≥18 years) with an onset of pregnancy from April 1, 2016, who had given birth to a singleton baby up to March 31, 2018, and who had a pre-existing mental disorder, defined as contacts with secondary mental health care in the 10 years immediately before pregnancy. The primary outcome was acute relapse, defined as psychiatric hospital admission or crisis resolution team contact in the postnatal period (first year after birth). Secondary outcomes included any secondary mental health care in the perinatal period (pregnancy and postnatal period) and obstetric and neonatal outcomes. Outcomes were compared according to whether a community perinatal mental health team was available before pregnancy, with odds ratios (ORs) adjusted for time trends and maternal characteristics (adjORs). Of 807 798 maternity episodes in England, we identified 780 026 eligible women with a singleton birth, of whom 70 323 (9·0%) had a pre-existing mental disorder. A postnatal acute relapse was found in 1117 (3·6%) of 31 276 women where a community perinatal mental health team was available and in 1745 (4·5%) of 39 047 women where one was unavailable (adjOR 0·77, 95% CI 0·64-0·92; p=0·0038). Perinatal access to any secondary mental health care was found in 9888 (31·6%) of 31 276 women where a community perinatal mental health team was available and 10 033 (25·7%) of 39 047 women where one was not (adjOR 1·35, 95% CI 1·23-1·49; p<0·0001). Risk of stillbirth and neonatal death was higher where a community perinatal mental health team was available (165 [0·5%] of 30 980 women) than where it was not (151 [0·4%] of 38 693 women; adjOR 1·34, 95% CI 1·09-1·66; p=0·0063), as was the risk of a baby small for gestational age (2227 [7·2%] of 31 030 women vs 2542 [6·6%] of 38 762 women; adjOR 1·10, 1·02-1·20; p=0·016), whereas preterm birth risk was lower (3167 [10·1%] of 31 206 women vs 4341 [11·1%] of 38 961; adjOR 0·86, 0·74-0·99; p=0·032). The regional availability of community perinatal mental health teams reduced the postnatal risk of acute relapse and increased the overall use of secondary mental health care. Community perinatal mental health teams should have close links with maternity services to avoid intensive psychiatric support overshadowing obstetric and neonatal risks. The National Institute for Health and Care Research.

The Dutch Cardio-Oncology cohort: Incidence of cardiovascular disease predisposes to a higher cancer mortality rate

Abstract Background Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. The relationship between the two diseases is complex and multi-factorial, with both diseases sharing risk factors and influencing each other's pathogenesis and progression. Given this interaction and the high prevalence of both CVD and cancer, it is crucial to understand the impact of CVD incidence on cancer mortality and to evaluate which CVD patients are at highest risk. This study aims to evaluate which patients with incidence cardiovascular disease have a higher risk of malignancy-related mortality, stratified for type of cardiovascular disease and compared to the general population without cardiovascular diseases. Methods We performed a national population-based cohort study with incidence CVD patients, in the Netherlands between January 2000 and December 2005. A control group was selected from the entire Dutch population using a genetic matching algorithm, which consists of the closest match for age and sex, and a propensity scores for country of birth. Both CVD and control patients were older than 18 years and did not have current diagnosis or a history of CVD and malignancies in the 5 years before inclusion. Mortality data were evaluated after data linkage of national registries from Dutch Hospital Data and Statistics Netherlands until December 2020. Cox proportional hazard models were performed to evaluate mortality risk. Results A total of 2 240 879 participants were included with a mean follow-up of 12 years (sd 7.6), of which 738 666 developed CVD. Mean age was 70.5 years (sd 14.8) for CVD patients and 66.4 years (sd 15.9) for control patients. Amongst CVD patients, 492 551 (66.7%) died within follow-up, in 90 982 (12.3%) malignacies were the primary cause. For control patients, this was 641 117 (42.7%) and 169 180 (11.3%), respectively. Correcting for follow-up time, malignancy-related mortality incidence rates per 1000 person years were 118 for patients with CVD and 84 for control patients. The hazard of malignancy-related mortality was significantly higher in CVD patients compared to control patients (HR 1.42, 95% CI 1.41 – 1.43). The patients most at risk were those with venous diseases (i.e. phlebitis, venous embolism and thrombosis; HR 2.28 95% CI (2.20 – 2.36) and peripheral artery disease (HR 1.89, 95% CI 1.81 – 1.94). The incidence rate of malignancy related mortality was highest in patients with heart failure, with an incidence of 258 per 1000 person-years. Conclusions This is the first in depth study evaluating malignancy-related mortality in patients with newly developed CVD. Results show that CVD predisposes to a higher cancer mortality rate, especially in patients with venous and peripheral artery diseases. The interaction between CVD and cancer underlines the need to develop strategies for early detection and effective management of both diseases in this population.

Risk of uterine rupture in multiparous women after induction of labor with prostaglandin: A national population-based cohort study.

To assess whether, after induction of labor with prostaglandin, multiparous (≥2 para) women have an increased risk of uterine rupture compared with nulliparous or uniparous women. This was a retrospective population-based cohort study including women who underwent induction with prostaglandin in all maternity wards in Sweden between May 1996 and December 2019 (n = 56 784). The study cohort was obtained by using data from the Swedish Medical Birth Register, which contains information from maternity and delivery records. The main outcome measure was uterine rupture. Overall, multiparous women induced with prostaglandin had an increased risk of uterine rupture compared with nulliparous women (adjusted odds ratio [OR], 3.33 [95% confidence interval (CI), 1.38-8.04]; P < 0.007). Multiparous women with no previous cesarean section (CS) induced with prostaglandin had more than three times higher risk of uterine rupture (crude OR, 3.55 [95% Cl, 1.48-8.53]; P = 0.005) compared with nulliparous women and four times higher risk compared with uniparous women (OR, 4.10 [95% CI, 1.12-15.00]; P < 0.033). Multiparous women with previous CS had a decreased risk of uterine rupture compared with uniparous women with one previous CS (crude OR, 0.41 [95% Cl, 0.21-0.78]; P = 0.007). Our study implies that multiparity in women with no previous CS is a risk factor for uterine rupture when induced with prostaglandin. This should be taken into consideration when deciding on the appropriate method of induction.

Risk of Therapy-Related Acute Myeloid Leukemia (t-AML) in Adolescent and Young Adults Cancer Patients Treated with Chemotherapy with or without Radiotherapy: A National Population-Based Cohort Study Using SEER Registry

INTRODUCTION The risk of treatment-related acute myeloid leukemia (t-AML) in adolescents and young adults (AYA) with first cancers treated with chemotherapy with or without radiation is not well characterized. We analyzed Surveillance, Epidemiology and End Result (SEER) data for the past 45-years (1975-2020) to identify the overall risk of t-AML in treated AYA cancer patients (pts) and by index cancer sites as well as latency periods. METHOD We analyzed NCI's SEER-8 registries. ICD-O-3/WHO-2008 codes were used to identify pts with index cancer types between the ages of 15-39 years (AYA), treated with either chemotherapy or radiotherapy, and with a subsequent diagnosis of acute myeloid leukemia (AML) at least one year after index cancer, between January 1975 and December 2020. The risk of t-AML was estimated by standardized incidence ratio (SIR), defined as the ratio of observed t-AML-cases in the AYA-with-cancer, to the expected number of AML-cases in the matched general US population. A reference rate file for AML incidence in age, gender, race and calendar-year matched US population is available in SEERStat software. A Poisson distribution of observed t-AML was assumed for the calculation of 95% confidence intervals (CIs). A P-value &amp;lt;.05 was considered statistically significant. We stratified the risk of t-AML for index cancer types with ten or more pts, by attained-calendar-years, and latency at multiple time intervals (Table-1) from index cancer diagnosis. RESULT Among 102,879 AYA cancer pts eligible for analysis, 236 pts developed t-AML with SIR of 6.19 (95%CI: 5.43-7.04, P &amp;lt;.05) with excess risk of 1.46 per-10000 person-years (pyrs). (Table-1). We stratified risk for index cancer types with at least ten patients developing t-AML, these included breast, Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), testicular, thyroid, bone and joint, and soft tissue including heart. As a general trend, risk of t-AML was highest during 1-3 years after index cancer diagnosis compared to subsequent latency periods. However, risk for t-AML was significantly greater than the matched-general US population even after 20-40 years of breast cancer, HL, and NHL (Table-1). When stratified by attained calendar-year periods (1975-1985, 1986-1995, 1996-2005, 2006-2015, 2016-2020), risk for t-AML was higher than general population in all time periods. However, overall SIR was comparatively lower for recent time periods, particularly lowest during 2016-2020 [SIR: 3.49 (2.51-4.72, P &amp;lt;.05)]. Notably, the highest risk for t-AML in 2016-2020 was observed with index cancer of soft tissue including heart [SIR: 10.12 (1.23-36.57), P &amp;lt;.05]. CONCLUSION In this study spanning between 1975-2020, we observed the risk of t-AML trending down among AYA in recent years, albeit higher than the age matched general population. The risk of t-AML remained significantly elevated even after 20-40 from diagnosis of breast cancer, HL and NHL. Since these pts likely received radiation and older (higher intensity) chemotherapy based-regimens, it is essential to analyze the long-term impact of newer therapies for these cancers and assess the risk of t-AML in future studies.

Treatment-related acute toxicity with adjuvant systemic treatment among patients with HER2-positive early invasive breast cancer: a national population-based cohort study

ObjectiveAlthough adjuvant trastuzumab-based treatment (TBT) improves survival for patients with HER2-positive early invasive breast cancer (EIBC), risk of toxicity grows as patient age increases. We examined use of TBT and...

Maternal Hypertensive Disorder of Pregnancy and Mortality in Offspring From Birth to Young Adulthood: National Population-based Cohort Study

(BMJ 2022;379:e072157) A large portion of pregnancies are affected by hypertensive disorders of pregnancy (HDP), and they have been associated with poor outcomes during pregnancy, labor, and delivery, and for children later in life. This study aimed to understand the association between overall and specific maternal HDP with overall and cause-specific mortality in children from birth to adulthood. Secondary to this aim, this study also investigated whether diabetes and education have an additional effect on children’s mortality and whether the timing of onset for HDP makes a difference. Primary outcomes were all causes of death, and secondary outcomes were specific causes: cancer, mental or behavioral disorders, conditions originating in the perinatal period, congenital malformations and chromosomal abnormalities, external causes, and diseases related to cardiovascular function, infection or parasite, endocrine, nutritional, or metabolic function, nervous system or sense organs, respiratory system function, digestive system function, musculoskeletal system or connective tissue, or genitourinary system function.

General or Regional Anaesthesia for Postpartum Hemorrhage: A National Population-based Cohort Study

(Acta Anaesthesiol Scand. 2022;66:103–113) Postpartum hemorrhage (PPH) continues to be a life-threatening complication following delivery. Anesthesia is required for the treatment of PPH when emptying the uterine cavity or manual placenta removal, and the choice between using general or regional anesthesia is impacted by factors such as airway, existing epidural, hypovolemia, and tradition. This study aimed to describe the variation in anesthesia for PPH treatment procedures as well as the occurrence of aspiration and difficult or failed intubation for Danish nationals between 2010 and 2015.

Obstetric and neonatal outcomes in pregnant women with and without a history of specialist mental health care: a national population-based cohort study using linked routinely collected data in England

Pregnant women with pre-existing mental illnesses have increased risks of adverse obstetric and neonatal outcomes compared with pregnant women without pre-existing mental illnesses. We aimed to estimate these differences in risks according to the highest level of pre-pregnancy specialist mental health care, defined as psychiatric hospital admission, crisis resolution team (CRT) contact, or specialist community care only, and the timing of the most recent care episode in the 7 years before pregnancy. Hospital and birth registration records of women with singleton births between April 1, 2014, and March 31, 2018 in England were linked to records of babies and records from specialist mental health services provided by the England National Health Service, a publicly funded health-care system. We compared the risks of adverse pregnancy outcomes, including fetal and neonatal death, preterm birth, and babies being born small for gestational age (SGA; birthweight <10th percentile), and composite indicators for neonatal adverse outcomes and maternal morbidity, between women with and without a history of contact with specialist mental health care. We calculated odds ratios adjusted for maternal characteristics (aORs), using logistic regression. Of 2 081 043 included women (mean age 30·0 years; range 18-55 years; 77·7% White, 11·4% South Asian, 4·7% Black, and 6·2% mixed or other ethnic background), 151 770 (7·3%) had at least one pre-pregnancy specialist mental health-care contact. 7247 (0·3%) had been admitted to a psychiatric hospital, 29 770 (1·4%) had CRT contact, and 114 753 (5·5%) had community care only. With a pre-pregnancy mental health-care contact, risk of stillbirth or neonatal death within 7 days of birth was not significantly increased (0·45-0·49%; aOR 1·11, 95% CI 0·99-1·24): risk of preterm birth (<37 weeks) increased (6·5-9·8%; aOR 1·53, 1·35-1·73), as did risk of SGA (6·2- 7·5%; aOR 1·34, 1·30-1·37) and neonatal adverse outcomes (6·4-8·4%; aOR 1·37, 1·21-1·55). With a pre-pregnancy mental health-care contact, risk of maternal morbidity increased slightly from 0·9% to 1·0% (aOR 1·18, 1·12-1·25). Overall, risks were highest for women who had a psychiatric hospital admission any time or a mental health-care contact in the year before pregnancy. Information about the level and timing of pre-pregnancy specialist mental health-care contacts helps to identify women at increased risk of adverse obstetric and neonatal outcomes. These women are most likely to benefit from dedicated community perinatal mental health teams working closely with maternity services to provide integrated care. National Institute for Health Research.

Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National Population-Based Cohort Study.

Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear. We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models. A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively. The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.

Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation.

Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating KIT mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.

Completeness of endocrine therapy information in the Primary Care Prescription Database (PCPD) and secondary care treatment datasets: A national population-based cohort study using routine healthcare data

BackgroundEndocrine therapy (ET) is a widely used treatment for breast cancer. In the UK, use is typically initiated in secondary care, with subsequent treatment in primary care. Evaluating use of ET depends on data sources containing accurate and complete information. This study aimed to evaluate the completeness and consistency of ET recorded in primary and secondary care data (SCD) and determine the value of combining data sources in describing use of ET. MethodsThis cohort study included women (50 + years) diagnosed with hormone receptor-positive invasive breast cancer in England, April-2015 to December-2019. Concordance of ET recorded in SCD and the Primary Care Prescription Database (PCPD) was evaluated. Factors associated with recording of ET in each setting were assessed using statistical models. ResultsOverall 110,529 women were included. 94% had ET recorded in either SCD or PCPD. ET captured in SCD varied from 3% (in Systemic Anti-Cancer Therapy data) to 52% (in the Cancer Outcomes and Services Dataset; COSD). By contrast, 93% of patients had an ET prescription in PCPD. Among patients with ET recorded, this was not captured in COSD for 45%. Capture in COSD was lowest for younger women, those with no comorbidity/frailty, with lower stage or HER2-positive disease, or with other treatments recorded. Overall concordance between COSD and PCPD was 57%, but varied substantially across NHS trusts (lowest decile≤28%; highest decile≥86%). Among women with ET recorded in both settings, the earliest record was in COSD for 97%; 59% of initial ET prescriptions recorded in COSD were not captured in PCPD. Combining PCPD and COSD data enabled estimation of ET duration. ConclusionsPCPD is vital for understanding the use of ET within this population. Completeness of SCD could be improved by ensuring information on first ET prescription is recorded. PCPD (linked to SCD) is a valuable resource for examining patterns of care for patients with cancer, including treatment duration and adherence.

Defunctioning stoma in anterior resection for rectal cancer does not impact anastomotic leakage: a national population-based cohort study

BackgroundAnterior resection (AR) is considered the gold standard for curative cancer treatment in the middle and upper rectum. The goal of the sphincter-preserving procedure, such as AR, is vulnerable to anastomotic leak (AL) complications. Defunctioning stoma (DS) became the protective measure against AL. Often a defunctioning loop-ileostomy is used, which is associated with substantial morbidity. However, not much is known if the routine use of DS reduces the overall incidence of AL.MethodsElective patients subjected to AR in 2007–2009 and 2016-18 were recruited from the Swedish colorectal cancer registry (SCRCR). Patient characteristics, including DS status and occurrence of AL, were analyzed. In addition, independent risk factors for AL were investigated by multivariable regression.ResultsThe statistical increase of DS from 71.6% in 2007–2009 to 76.7% in 2016–2018 did not impact the incidence of AL (9.2% and 8.2%), respectively. DLI was constructed in more than 35% of high-located tumors ≥ 11 cm from the anal verge. Multivariable analysis showed that male gender, ASA 3–4, BMI > 30 kg/m2, and neoadjuvant therapy were independent risk factors for AL.ConclusionRoutine DS did not decrease overall AL after AR. A selective decision algorithm for DS construction is needed to protect from AL and mitigate DS morbidities.

Association between medical complications according to continuity of care and medication adherence in patients with hypertension in Korea: a national population-based cohort study

ObjectivesTo analyse the differences in hypertensive complications according to continuity of care (COC) and medication adherence in patients with hypertension.DesignA national population-based retrospective cohort study.SettingSecondary data analysis using National insurance...

Risk Factors for Postoperative Complications Following Resection of Colorectal Liver Metastases and the Impact on Long-Term Survival: A Population-Based National Cohort Study

BackgroundPostoperative complications (POCs) following resection of colorectal liver metastases (CRLM) are common. The objective of this study was to evaluate risk factors for developing complications and their impact on survival considering prognostic factors of the primary tumor, metastatic pattern and treatment in a well-defined national cohort.MethodsPatients treated with resection for CRLM that was also radically resected for their primary colorectal cancer (diagnosed in 2009–2013) were identified in Swedish national registers. Liver resections were categorized according to extent of surgery (Category I–IV). Risk factors for developing POCs as well as prognostic impact of POCs were evaluated in multivariable analyses. A subgroup analysis of minor resections was performed to evaluate POCs after laparoscopic surgery.ResultsPOCs were registered for 24% (276/1144) of all patients after CRLM resection. Major resection was a risk factor for POCs in multivariable analysis (IRR 1.76; P = 0.001). Comparing laparoscopic and open resections in the subgroup analysis of small resections, 6% (4/68) in the laparoscopic group developed POCs compared to 18% (51/289) after open resection (IRR 0.32; P = 0.024). POCs were associated with a 27% increased excess mortality rate (EMRR 1.27; P = 0.044). However, primary tumor characteristics, tumor burden in the liver, extrahepatic spread, extent of liver resection and radicality had higher impact on survival.ConclusionMinimal invasive resections were associated with a decreased risk of POCs following resection of CRLM which should be considered in surgical strategy. Postoperative complications were associated with a moderate risk for inferior survival.