Nationwide Population-based Study Research Articles

Estimating vaccine effectiveness against COVID-19 using cause-specific sick leave as an indicator: a nationwide population-based cohort study, Norway, July 2021 – December 2022

BackgroundDue to changes in testing policy and increased use of rapid tests, other indicators for SARS-CoV-2 infections are needed to monitor vaccine effectiveness (VE). We aimed to estimate VE against COVID-19 sick leave (> 3 days, certified by a medical professional) among employed individuals (25–64-years-old) in Norway.MethodsWe performed a nationwide cohort study by collating data from the Emergency preparedness register for COVID-19. We used adjusted Cox proportional hazard models with vaccine status as a time-varying covariate and presented results as adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals. Separate models were run against sick leave and against SARS-CoV-2 infections during the Delta period (June-December 2021), and against sick leave during the Omicron period (January-December 2022) when SARS-CoV-2 PCR-testing was replaced by rapid self-tests and infections were underreported.ResultsWe included 2,236,419 individuals during the Delta period, of whom 73,776 (3.3%) had a reported infection and 54,334 (2.4%) were registered with sick leave. Of the 2,206,952 included individuals in the Omicron period, 300,140 (13.6%) were registered with sick leave. During the Delta period, 55% (26,611) of individuals who had registered sick leave also had a positive test, compared to 32% (96,445) during the Omicron period. The VE against sick leave during the Delta period followed a similar waning pattern to that against SARS-CoV-2 infections. After the second and third dose, the lowest aHRs were estimated for 2–7 days after vaccination for both sick leave (0.25; 95%CI 0.24–0.26 and 0.26; 95% CI 0.24–0.29) and infection ( 0.16; 95% CI 0.15–0.17 and 0.18; 95% CI 0.16–0.19) respectively. During the Omicron period, aHRs for sick leave were higher than during the Delta period, but the lowest aHRs were still found in 2–7 weeks after receiving the second (0.61; 95% CI 0.59–0.64) or third dose (0.63; 95% CI 0.62–0.64).ConclusionOur results showed that sick leave could be a relevant indicator for VE in the surveillance of COVID-19 and a finding that may be important in the surveillance of other respiratory infection.

Incidence of seropositive and seronegative rheumatoid arthritis in Denmark: a nationwide population-based study

Objective To investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition. Method This nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year. Results An increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period. Conclusions The IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors.

Maternal cigarette smoking before or during pregnancy increases the risk of severe neonatal morbidity after delivery: a nationwide population-based retrospective cohort study

BackgroundThe association of maternal cigarette smoking during pregnancy with severe neonatal morbidity (SNM) is still inconclusive. We aimed to examine the associations of the timing and the intensity of maternal...

Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study.

Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

Long-term oncological outcomes of follicular thyroid cancer in adolescents and young adults: A nationwide population-based study.

Follicular thyroid carcinoma (FTC) in adolescents and young adults (AYAs) is rare and data on long-term oncological outcomes are scarce. This study aimed to describe the long-term recurrence and survival rates of AYAs with FTC, and identify risk factors for recurrence. This is a retrospective cohort study combining two national databases, including all patients aged 15-39years, diagnosed with FTC in The Netherlands between 2000 and 2016. Age, sex, tumor size, focality, positive margins, angioinvasion, pT-stage, and pN-stage were included in a Cox proportional hazard model to identify risk factors for recurrence. We included 192 patients. Median age was 31.0years (IQR 24.7-36.3) and the male to female ratio was 1:4.1. Most patients presented with a minimally invasive FTC (MI-FTC) (95%). Five patients presented with synchronous metastases (2.6%), including two with locoregional metastases (1%) and three with distant metastases (1.6%). During a median follow-up of 12.0years, three patients developed a recurrence (1.6%), of which one patient developed a local recurrence (33%), and two patients a distant recurrence (67%). Five patients died during follow-up (2.6%). Cause of death was not captured. A Cox proportional hazard model could not be performed due to the low number of recurrences. FTC in AYAs is generally characterized as a low-risk tumor, as it exhibits a very low recurrence rate, a high overall survival, and it typically presents as MI-FTC without synchronous metastases. These findings underscore the favorable long-term oncological prognosis of FTC in AYAs.

Income dynamics and risk of colorectal cancer in individuals with type 2 diabetes: a nationwide population-based cohort study.

Individuals with type 2 diabetes (T2D) have increased colorectal cancer (CRC) risk, but it is unknown whether income dynamics are associated with CRC risk in these individuals. We examined whether persistent low- or high-income and income changes are associated with CRC risk in non-elderly adults with T2D. Using nationally representative data from the Korean Health Insurance Service database, 1,909,492 adults aged 30 to 64 years with T2D and no history of cancer were included between 2009 and 2012 (median follow-up of 7.8 years). We determined income levels based on health insurance premiums and assessed annual income quartiles for the baseline year and the four preceding years. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment. Persistent low income (i.e., lowest income quartile) was associated with increased CRC risk (HRn=5years vs. n=0years 1.11, 95% CI 1.04-1.18; P for trend=0.004). Income declines (i.e., a decrease≥25% in income quantile) were also associated with increased CRC risk (HR≥2 vs. 0 declines 1.10, 95% CI 1.05-1.16; p for trend=0.001). In contrast, persistent high income (i.e., highest income quartile) was associated with decreased CRC risk (HRn=5years vs. n=0years 0.81, 95% CI 0.73-0.89; p for trend<0.0001), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.53-0.78) and distal colon cancer (HR 0.70, 95% CI 0.57-0.86). Our findings underscore the need for increased public policy awareness of the association between income dynamics and CRC risk in adults with T2D.

Intrapartum fetal monitoring practices in Norway: A population-based study

ObjectiveTo describe intrapartum fetal monitoring methods used in all births in Norway in 2019–2020, assess adherence to national guidelines, investigate variation by women’s risk status, and explore associations influencing monitoring practices. MethodsA nationwide population-based study. We collected data about all pregnancies with a gestational age ≥ 22 weeks during 2019–2020 from the Medical Birth Registry of Norway. We used descriptive analyses, stratified for risk status, to examine fetal monitoring methods used in all deliveries. Univariable and multivariable logistic regression models were used to determine factors associated with monitoring with cardiotocography (CTG) in low-risk, straightforward births. ResultsIn total, 14 285 (14%) deliveries were monitored with only intermittent auscultation (IA), 46214 (46%) with only CTG, and 33417 (34%) with IA and CTG combined. Four percent (2 067/50 533) of women with risk factors were monitored with IA only. Half (10589/21 282) of the low-risk women with straightforward births were monitored with CTG. Maternal and fetal characteristics, size of the birth unit and regional practices influenced use of CTG monitoring in this group. ConclusionsMost births are monitored with CTG only, or combined with IA. Half the women with low-risk pregnancies and straightforward births were monitored with CTG although national guidelines recommending IA.

The impact of hospital saturation on non-COVID-19 hospital mortality during the pandemic in France: a national population-based cohort study

BackgroundA previous study reported significant excess mortality among non-COVID-19 patients due to disrupted surgical care caused by resource prioritization for COVID-19 cases in France. The primary objective was to investigate if a similar impact occurred for medical conditions and determine the effect of hospital saturation on non-COVID-19 hospital mortality during the first year of the pandemic in France.MethodsWe conducted a nationwide population-based cohort study including all adult patients hospitalized for non-COVID-19 acute medical conditions in France between March 1, 2020 and 31 May, 2020 (1st wave) and September 1, 2020 and December 31, 2020 (2nd wave). Hospital saturation was categorized into four levels based on weekly bed occupancy for COVID-19: no saturation (< 5%), low saturation (> 5% and ≤ 15%), moderate saturation (> 15% and ≤ 30%), and high saturation (> 30%). Multivariate generalized linear model analyzed the association between hospital saturation and mortality with adjustment for age, sex, COVID-19 wave, Charlson Comorbidity Index, case-mix, source of hospital admission, ICU admission, category of hospital and region of residence.ResultsA total of 2,264,871 adult patients were hospitalized for acute medical conditions. In the multivariate analysis, the hospital mortality was significantly higher in low saturated hospitals (adjusted Odds Ratio/aOR = 1.05, 95% CI [1.34–1.07], P < .001), moderate saturated hospitals (aOR = 1.12, 95% CI [1.09–1.14], P < .001), and highly saturated hospitals (aOR = 1.25, 95% CI [1.21–1.30], P < .001) compared to non-saturated hospitals. The proportion of deaths outside ICU was higher in highly saturated hospitals (87%) compared to non-, low- or moderate saturated hospitals (81–84%). The negative impact of hospital saturation on mortality was more pronounced in patients older than 65 years, those with fewer comorbidities (Charlson 1–2 and 3 vs. 0), patients with cancer, nervous and mental diseases, those admitted from home or through the emergency room (compared to transfers from other hospital wards), and those not admitted to the intensive care unit.ConclusionsOur study reveals a noteworthy “dose-effect” relationship: as hospital saturation intensifies, the non-COVID-19 hospital mortality risk also increases. These results raise concerns regarding hospitals’ resilience and patient safety, underscoring the importance of identifying targeted strategies to enhance resilience for the future, particularly for high-risk patients.

Inflammatory eye disease is a risk factor for future microscopic colitis: A nationwide population-based matched case control study.

Microscopic colitis (MC) is an inflammatory disorder of the colon. To date, the relationship between inflammatory eye diseases and MC is unclear. To assess whether inflammatory eye disease (iridocyclitis and episcleritis) is a risk factor for MC. We conducted a nationwide matched case control study in Sweden leveraging the ESPRESSO-study (a Swedish database containing data on all biopsies from the gastrointestinal tract from 1965 to 2017). In total, we identified 14,338 patients with biopsy-verified MC (diagnosed from 1981 to 2017). Patients with MC were matched (by age, sex, county and year of birth) with 68,753 controls from the general population and the occurrence of preceding inflammatory eye diseases (defined as diagnosis of episcleritis or iridocyclitis) in the two groups was compared. Multivariable adjusted odds ratios (aORs) were calculated using conditional logistic regression conditioned on the matching variables. A majority of patients with MC were women (71.9%) and the median age at MC diagnosis was 63.3years (interquartile range (IQR)=50.7-72.6). Some 225 (1.6%) MC patients had an earlier record of inflammatory eye disease compared with 614 (0.9%) in controls. These figures corresponded to an aOR of 1.77 (95% CI=1.52-2.07) for inflammatory eye diseases in patients with MC. Compared to siblings, the aOR for previous inflammatory eye diseases in MC was 1.52 (95% CI=1.17-1.98) and patients treated with budesonide, as a proxy for clinically significant disease, had a somewhat higher aOR for previous inflammatory eye diseases. Inflammatory eye diseases are more common in patients subsequently being diagnosed with MC. Our findings highlight that these conditions may have shared causes and inflammatory pathways and are of clinical interest to gastroenterologists, ophthalmologists and general practitioners.

Attention-deficit/hyperactivity disorder and subsequent diagnoses of major psychiatric disorders: a nationwide population-based study.

We evaluated the risk of being diagnosed with various psychiatric disorders after an attention-deficit/hyperactivity disorder (ADHD) diagnosis using data from South Korea's National Health Insurance Service from 2002 to 2019, which covers approximately 97% of the country's population. ADHD and control groups were selected after propensity score matching was performed for individuals diagnosed with ADHD and their age- and sex-matched counterparts from the general population. Comorbid psychiatric disorders included depressive disorder, bipolar disorder, tic disorder, and schizophrenia. The incidence of newly diagnosed psychiatric disorders was compared between the groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and adjusted for ADHD medication prescription. After matching, 353,898 individuals were assigned to each of the two groups. Compared to the control group, the ADHD group showed a significantly higher risk of being subsequently diagnosed with depressive disorder, bipolar disorder, schizophrenia, and tic disorder. The onset age of depressive disorder, bipolar disorder, and schizophrenia in the ADHD group was 16-17 years, approximately 5 years earlier than that in the control group. The risk for depression was the highest in individuals with high income levels, and that for schizophrenia was the highest among rural patients. The median length of the follow-up time until the diagnosis of each comorbid psychiatric disorder was 7.53, 8.43, 8.53, and 8.34 years for depressive disorder, bipolar disorder, schizophrenia, and tic disorder, respectively. Individuals with ADHD had an overall higher risk of being diagnosed with subsequent psychiatric disorders than did the controls. Hence, they should be carefully screened for other psychiatric symptoms from an early age and followed up for an extended duration, along with appropriate interventions for ADHD symptoms, including psychosocial treatments and educational approaches.

Prevalence, trends, and specialized palliative care utilization in Taiwanese children and young adults with life-limiting conditions between 2008 and 2017: a nationwide population-based study

BackgroundPrevious studies have shown a growing need for pediatric palliative care, but there is a lack of knowledge in many countries concerning prevalence of service use among children and young adults with life-limiting conditions. This study aimed to estimate (1) the annual prevalence of children and young adults with a life-limiting condition, and (2) their specialized palliative care and other healthcare utilization.MethodsData from the Health and Welfare Data Science Center in Taiwan were used. All children and young adults aged 0–25 years recorded in inpatient or outpatient data, and infants aged < 1 year in death data with a life-limiting condition diagnostic code from 2008 to 2017 were recruited. Poisson regression was used to estimate the crude and adjusted relative risk of prevalence of life-limiting conditions with 95% confidence intervals, adjusted for age and sex, and to evaluate the trend in prevalence of each life-limiting diagnostic groups, in specialized palliative care and other service use.ResultsData contained 236,250 individuals with a life-limiting condition, of which oncological and congenital abnormalities were the most common. There was an annualized increase over 10 years in the prevalence of life-limiting conditions of 36.4%, from 45,311 cases (59.4 per 10,000 population) to 52,226 cases (81.0 per 10,000 population), with the highest prevalence in individuals aged 21–25 years. All diagnostic groups showed significant increases in prevalence (p < .001) with the exception of oncology, circulatory, and “other” group. Specialized palliative care services, including family consultation, shared care, home visits have increased in use over time (p < .001), while inpatient hospice has slightly decreased. The highest prevalence of healthcare use was for traditional Chinese medicine (237.1 per 1,000 population in 2017), but this decreased over time (p < .001).ConclusionsDue to a growing trend towards multidisciplinary care, healthcare professionals and policymakers must engage and take action to expand specialized palliative care and integrate delivery of other healthcare services. Traditional Chinese medicine having a decreasing slope, yet still the highest prevalence of use, needs further attention.

O-200 Association between proton pump inhibitors use and the risk of maternal infections during pregnancy and postpartum: a Swedish population-based cohort study

Abstract Study question Is there an association between use of proton pump inhibitors (PPIs) and maternal infection during or after pregnancy and subsequent pregnancy complications? Summary answer Use of PPIs in the 3 months before pregnancy or during the first trimester was associated with an elevated risk of maternal infection. What is known already PPIs alter gastric acidity and the gut microbiome, which may increase infection risks in the general population, but their impact on pregnant women is unknown. Study design, size, duration We conducted a Nationwide population-based cohort study using data from Swedish healthcare registers. PPIs use was defined as ≥ 1 prescription fill of a PPI in the 90 days before the first day of the last menstrual period (LMP) to the end of the 1st trimester (LMP+97 days). Maternal infections were identified from the start of the 2nd trimester to 90 days postpartum and classified as mild, moderate/ severe infections, and infection-related pregnancy complications. Participants/materials, setting, methods All pregnancies resulting in live or stillbirths between 2006 to 2019 in Sweden, identified using the Medical Birth Register. Log-binomial regression was used to estimate associations (relative risk (RR) and 95% confidence intervals (CI)) between PPIs and maternal infection, adjusting for potential confounders including birth year, maternal age at delivery, early pregnancy BMI, comorbidities, smoking in early pregnancy, maternal country of birth, maternal education, and parity. Main results and the role of chance Among 1,510,560 pregnant women, 42,599 (2.8%) used PPIs, and use increased over the study period time from 1.5% in 2006 to 3.44% in 2019. Compared to pregnant women without PPI use, those with PPI use had higher rates and risks of any infection (49.7% vs 36.8%; adjusted RR 1.30, 95%CI 1.29-1.32), mild infection (20.9% vs 16.1%; adjusted RR 1.30, 95%CI 1.28-1.33), moderate to severe infection (23.4% vs 15%; adjusted RR 1.47, 95%CI 1.45-1.50), and infection-related pregnancy complications (11.2% vs 9.2; adjusted RR 1.12, 95%CI 1.09-1.15). Conclusion Our results show an association between PPI use and an elevated risk of infection in pregnant women. Next steps include the further investigation into the infection types. PPI therapy has benefits and drawbacks that should be carefully weighed, especially in patients who are prone to infections. While our study highlights potential concerns, it does not imply that all pregnant women are at increased risk. More research is needed to understand the underlying mechanisms and assess potential preventive measures. Prescribing PPIs during pregnancy should be determined on a case-by-case basis, considering the patient’s individual health state. We acknowledge the necessity for caution, particularly in vulnerable populations, and more research is needed to demonstrate clinical correlations. Limitations, reasons for caution Potential confounding by indication due to underlying morbidities cannot be fully accounted for. Further research is required to establish clinical connections. Wider implications of the findings Clinicians should carefully weigh the benefits of PPI therapy during pregnancy, particularly in patients prone to infections. Trial registration number not applicable

Prevalence of congenital cryptorchidism in China: A nationwide population-based surveillance study, 2007-2021.

Despite cryptorchidism being a common genital abnormality in male newborns with significant prevalence variations globally, there is a notable scarcity of epidemiological data on this condition in China. This study aimed to delineate the prevalence pattern of cryptorchidism in Chinese population over the past 15 years using nationwide surveillance data. Data from the China National Population-based Birth Defects Surveillance System (2007-2021) were analyzed to calculate the prevalence rates of cryptorchidism, stratified by birth year, maternal age, maternal residence, and geographic region. Adjusted prevalence rate ratios were computed using Poisson regression, while trends in prevalence and average annual percent change (AAPC) were assessed using the joinpoint regression model. During the study period, a total of 1,833 cases of cryptorchidism were identified among 2,565,964 full-term male births, resulting in prevalence rates of 7.14, 5.60, and 1.54 per 10,000 births for overall, isolated, and associated cryptorchidism, respectively. The overall prevalence increased from 3.86 to 11.20 per 10,000 births, with an AAPC of 7.9% (95% confidence interval: 5.5-11.0). Significant variations were observed across maternal age (<20 years, 7.62/10,000; 20-24 years, 6.14/10,000; 25-29 years, 6.96/10,000; 30-34 years, 7.48/10,000; ≥35 years, 9.22/10,000), maternal residence (urban vs. rural, 10.99/10,000vs. 2.86/10,000), and geographic region (eastern, 12.38/10,000; central, 2.36/10,000; western, 2.63/10,000). Approximately one-third of cryptorchidism cases were bilaterally, while two-thirds were unilateral. Commonly observed associated abnormalities included congenital hydrocele testis, as well as anomalies in the genital organs, circulatory system, and musculoskeletal system. Despite lower rates compared to other countries, the increasing trend in prevalence of cryptorchidism necessitates further investigation and intervention.

Colorectal cancer and association with anaerobic bacteraemia: A Danish nationwide population-based cohort study

We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer. A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference. Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference). This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer.

Association between Pentosan Polysulfate and Subsequent Maculopathy: Insights from a Nationwide Population-Based Study in Korea

PurposeTo determine the association between pentosan polysulfate (PPS) use and the subsequent development of maculopathy in Asian population. DesignA nationwide population-based retrospective cohort study using the Health Insurance Review and Assessment Service database. Participants103,553 individuals in the PPS user group and 205,792 individuals in the PPS non-user group, all newly diagnosed with cystitis between 2009 and 2020. MethodsThe association between PPS use and maculopathy was evaluated using a time dependent Cox proportional hazard model. Additionally, two sensitivity analyses were conducted by defining PPS users as individuals with an observation period over 6 months from the initial prescription or those with cumulative dose exceeding 9 g, employing the same analysis. Main Outcome MeasuresThe outcome measures included the hazard ratios (HR) representing the association between PPS use and maculopathy. ResultsPPS use was associated with an increased risk of subsequent maculopathy in univariate (HR, 1.7; 95% confidence intervals [CI], 1.66–1.75) and multivariate analysis (HR, 1.34; 95% CI, 1.31–1.38). These results were also confirmed in two sensitivity analyses. The mean cumulative dose of PPS for the cohort was 37.2 ± 76.7 g. ConclusionsIn this nationwide cohort study involving an Asian population, individuals with cystitis using PPS exhibit an increased risk of developing subsequent maculopathy.

Association between hospital procedure volume, socioeconomic status, comorbidities, and adverse events related to surgical abortion: a nationwide population-based cohort study

BackgroundLimited evidence exists on the influence of hospital procedure volume, socioeconomic status, and comorbidities on surgical abortion outcomes. ObjectiveOur study aimed to assess the association between hospital procedure volume, individual and neighborhood deprivation, comorbidities, and abortion-related adverse events. Study DesignA nationwide population-based cohort study of all women hospitalized for surgical abortion was conducted from January 1, 2018, to December 31, 2019 in France. Annual hospital procedure volume was categorized into four levels based on spline function visualization: very low (<80), low ([80-300[), high ([300-650[), and very high-volume (≥650) centers. The primary outcome was the occurrence of at least one surgical-related adverse event, including hemorrhage, retained products of conception, genital tract and pelvic infection, transfusion, fistulas and neighboring lesions, local hematoma, failure of abortion, admission to an intensive care unit or death. These events were monitored during the index stay and during a subsequent hospitalization up to 90 days. The secondary outcome encompassed general adverse events not directly linked to surgery. ResultsOf the 112,842 hospital stays, 4,951 (4.39%) had surgical-related adverse events and 256 (0.23%) had general adverse events. The multivariate analysis showed a volume-outcome relationship, with lower rates of surgical-related adverse events in very high-volume (2.25%, aOR=0.34, 95%CI [0.29-0.39], p<0.001), high-volume (4.24%, aOR=0.61, 95%CI [0.55-0.69], p<0.001), and low-volume (4.69%, aOR=0.81, 95%CI [0.75-0.88], p<0.001) when compared to very low-volume centers (6.65%). Individual socioeconomic status (aOR=1.69, 95%CI [1.47-1.94], p<0.001), neighborhood deprivation (aOR=1.31, 95% CI [1.22-1.39], p<0.001), and comorbidities (aOR=1.79, 95%CI [1.35-2.38], p<0.001) were associated with surgical-related adverse events. Conversely, the multivariate analysis of general adverse events did not reveal any volume-outcome relationship. ConclusionThe presence of a volume-outcome relationship underscores the need for enhanced safety standards in low-volume centers to ensure equity in women's safety during surgical abortions. However, our findings also highlight the complexity of this safety concern which involves multiple other factors including socioeconomic status and comorbidities that policymakers must consider.

Risk Factors for 90-Day Readmission Among Patients with Metastatic Spine Tumors in South Korea: A Nationwide Population-Based Study

Population-based studies on the cause of readmission within 90 days after surgery or radiotherapy for metastatic spine tumors are scarce. We aimed to investigate the risk factors for readmission within 90 days after initial surgical or radiation treatment for metastatic spine tumors. Patients who were diagnosed with metastatic spine tumors between 2012 and 2019 and underwent spinal magnetic resonance imaging within 1 year were classified according to treatment (surgical or radiotherapy groups), and the causes of the 90-day readmission and patient characteristics were compared. Overall, data from 15,815 patients (surgical group, 13,974 patients; radiotherapy group, 1,841 patients) were evaluated. Radiotherapy was preferred in younger and male patients with a high Charlson Comorbidity Index (CCI), whereas surgery was mainly performed in patients with lumbar metastasis. Radiotherapy, age of 30-69 years, male sex, and CCI > 1 increased the risk of 90-day readmission in patients with metastatic spine tumors. The main causes of 90-day readmission among patients with metastatic spine tumors who received radiotherapy included tumor recurrence, chemotherapy, radiotherapy, and treatment of other organ metastases with radiotherapy. These study findings offer a better understanding of the causes of readmission following radiotherapy or surgical treatment in patients with metastatic spine tumors, and these results can help reduce postoperative morbidity and medical costs among these patients.

Risk of Second Primary Cancer Among Patients with Cardio-Esophageal Cancer in Finland: A Nationwide Population-Based Study.

The occurrence of a second primary cancer (SPC) after primary esophageal carcinoma (EC) or gastric cardia carcinoma(GCC) is well acknowledged. However, previous research on the risk of SPC among these patients has been predominantly conducted in Asian countries. Yet, notable population-dependent variation in histological types and risk profiles exists. This register-based study assesses the histology-specific risk of SPC among individuals initially diagnosed with a first primary EC or GCC. We obtained data on 7197 patients diagnosed with EC/GCC in Finland between 1980 and 2022 from the Finnish Cancer Registry. Standardized incidence ratios (SIR) of SPC were subsequently calculated relatively to the cancer risk of the general population. The average and median follow-up times were 2.8 years and 10.5 months. Adenocarcinomas and squamous cell carcinomas comprised 57.8% (n = 4165) and 36.6% (n = 2631) of all cases, respectively. An increased SIR was noted among EC/GCC patients after 15-20 years of follow-up (SIR 1.49, 95% CI: 1.01-2.11). Among adenocarcinoma patients, an increased SIR for SPCs of the digestive organs was seen in the 40-54-year-old group (SIR 9.86, 95% CI: 3.62-21.45). Squamous cell carcinoma patients displayed increased SIRs for cancer of the mouth/pharynx (SIR 3.20, 95% CI: 1.17-6.95) and respiratory organs (1.77, 1.07-2.76). Healthcare professionals should be aware of the increased risk of SPCs occurring in the mouth/pharynx, respiratory and digestive organs in survivors of EC/GCC. Patients should be advised about this risk and remain alert for symptoms, even beyond the standard 5-year follow-up period.

Direct factor Xa inhibitors and the risk of cancer and cancer mortality: A Danish population-based cohort study.

Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran. This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period. In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.

Risk of pulmonary embolism and deep vein thrombosis following COVID-19: a nationwide cohort study.

Recent studies elucidate that coronavirus disease 2019 (COVID-19) patients may face a higher risk of cardiovascular complications. This study aimed to evaluate association of COVID-19 with the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT). This nationwide population-based retrospective cohort study included Korean adult citizens between January 2021 and March 2022 from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort. The Fine and Gray's regression with all-cause death as a competing event was adopted to evaluate PE and DVT risks after COVID-19. This study included a total of 1,601,835 COVID-19 patients and 14,011,285 matched individuals without COVID-19. The risk of PE (adjusted hazard ratio [aHR], 6.25; 95% confidence interval [CI], 3.67-10.66; p<0.001) and DVT (aHR, 3.05; 95% CI, 1.75-5.29; p<0.001) was higher in COVID-19 group in individuals without complete COVID-19 vaccination. In addition, individuals with complete COVID-19 vaccination still had a higher risk of COVID-19-related PE (aHR, 1.48; 95% CI, 1.15-1.88; p<0.001). However, COVID-19 was not a significant risk factor for DVT among those with complete COVID-19 vaccination. COVID-19 was identified as an independent factor that elevated PE and DVT risks, especially for individuals without complete COVID-19 vaccination.