Register-based Cohort Study Research Articles

Chitosan-covered tamponade for the treatment of postpartum hemorrhage: a registry-based cohort study assessing outcomes and risk factors for treatment failure

Abstract Background Postpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide. Intrauterine hemostatic devices are recommended when PPH does not respond to medical treatment. The objective of this study was to assess the factors leading to unsuccessful intrauterine therapy with a chitosan-covered tamponade (CT) for the treatment of PPH and to evaluate clinical outcomes based on real-world data. Methods This registry-based cohort study included all women treated with CT for PPH between January 2017 and June 2022 at a university clinic’s perinatal department. The endpoint was defined as the failure of CT, indicated by the requirement of further invasive procedures for ongoing hemorrhage after CT application. Medical records were reviewed and binary logistic regressions used to evaluate delivery mode, placenta previa, and placenta accreta spectrum as potential risk factors for CT treatment failure. Results The cohort consisted of 230 women, with successful CT treatment in 91.3%. The success rate for mild PPH was 100.0%, for moderate 95.5%, and for severe 84.2%. Five hysterectomies were performed in total. Placenta previa in cesarean sections was identified as the primary risk factor for CT treatment failure, increasing the odds about 7.5-fold (Odds Ratio: 7.48; 95% CI: 1.87–33.15) compared to cesarean sections without placenta previa. Furthermore, delays in CT insertion may also contribute to treatment failure. Conclusion CT serves as an intrauterine treatment for medically intractable PPH. Placenta previa significantly increases the risk of CT treatment failure in cesarean sections. Obstetricians should be particularly vigilant in managing patients with placenta previa and consider early use of CT or a combination of procedures. Trial registration This study was approved by the local Ethics Committee on 11/10/2021 (EA4/231/21).

Cesarean section and the gestational duration of subsequent pregnancies: A nationwide register-based cohort study

Introduction Preterm delivery risk is increased for women with a previous cesarean section, which are becoming more common worldwide. However, this risk is based on studies which have not fully accounted for selection bias, and the studied outcomes have been limited to the study of early deliveries. This study aimed to determine the impact of previous delivery modes on the incidence of deviant duration of subsequent pregnancies. Material and methods This retrospective cohort study used clinical data registered in the Swedish Medical Birth Register. 612 935 women with their first two pregnancies and 157 581 women with their first three pregnancies were included. The outcome was the gestational duration of the last pregnancy of the series, depending on previous delivery modes. The associations were analysed with multivariable logistic regression (with the gestational duration categorised) and survival models including Cox regression analyses. Results When using standard logistic regression, previous cesarean section was associated with an increased risk of both spontaneous preterm birth (adjusted odds ratio [aOR] 1.67, 95% CI 1.57–1.77) and postterm birth (aOR 1.55, 95% CI 1.49–1.62). However, the more appropriate survival models only showed an association between cesarean section and longer gestational duration of the subsequent pregnancy (adjusted hazard ratio 0.72, 95% CI 0.71–0.73). Conclusions The survival model handles bias related to management differences between the exposure and reference groups better than standard logistic regression, making it the statistical method of choice when conducting studies on this research topic. This study shows that the main association between cesarean section and the gestational duration of the subsequent pregnancy is the prolonging of it, which stands in contrast with previous research on the topic.

Sex differences in the impact of multimorbidity on long-term mortality for patients with colorectal cancer: a population registry-based cohort study.

Women have better survival than men patients with colorectal cancer (CRC), but the extent to which this is due to multimorbidity is unclear. A population-based study of 1843 patients diagnosed with CRC in Australia. Data included patient's demographics, multimorbidity, tumour histology, cancer stage, and treatment. We estimated the risks of all-cause mortality and cause-specific mortality due to cancer or non-cancer causes. Men had lower survival than women (P≤0.010) amongst those diagnosed at Stages I-III (15-year survival: 56.0% vs 68.0%, 48.5% vs 60.7%, 34.8% vs 47.5%, respectively), excepting Stage IV (14.4% vs 12.6%; P=0.18). Married men exhibit better survival than those who were never married (P=0.006). Heart attacks (9.9% vs 4.3%, P<0.001) and emphysema (4.8% vs 2.1%, P=0.004) were more prevalent in men than women. Comorbid stroke and high cholesterol (adjusted hazard ratio, AHR=2.22, 95% confidence interval, CI=1.17-4.21, P=0.014) and leukaemia (AHR=6.36, 95% CI=3.08-13.1, P<0.001) increased the risk of cancer death for men only. For women, diabetes increased the risk of all-cause death (AHR=1.38, 95% CI=1.02-1.86, P=0.039) and high blood pressure increased the risk of death due to non-cancer causes (AHR=2.00, 95% CI=1.36-2.94, P<0.001). Separate models of CRC care are needed for men and women with consideration of multimorbidity and social factors.

The effect of interdisciplinary treatment on sickness absence and disability pension among chronic pain patients on partial disability pension.

Studies evaluating the effects of interdisciplinary treatment (IDT) on sickness absence and disability pension (SA/DP) have yielded contradictory findings. Evidence indicates that positive treatment effects are restricted to patients with a poor SA/DP prognosis. This study therefore analyzed the effect of IDT in working age patients on partial disability pension, which is a group with a particularly poor prognosis. With data from 479 patients on partial disability pension, this register-based cohort study compared the effects of IDT to those of unspecified interventions. We considered two response variables: total net SA/DP days across the span of three years from the first visit to a Swedish specialist pain clinic, and the risk of having the maximum possible 1096 SA/DP days over the same period. Our results showed that both the total net SA/DP days (mean difference: 11; 95% confidence interval: -30 to 51) and the risk of 1096 SA/DP days (risk ratio: 1.0; 95% confidence interval: 0.6 to 1.4) were similar irrespective of intervention type. Under our theoretical model, we thereby found no support in favor of IDT over less intensive interventions in working age patients with partial DP. This raises questions about the specific criteria under which IDT proves effective.

Vaccination against measles-mumps-rubella and rates of non-targeted infectious disease hospitalisations: Nationwide register-based cohort studies in Denmark, Finland, Norway, and Sweden.

To investigate if receipt of measles-mumps-rubella (MMR) vaccine following the third dose of diphtheria-tetanus-acellular pertussis (DTaP3) is associated with reduced rates of non-targeted infectious disease hospitalisations. Register based cohort study following 1,397,027 children born in Denmark, Finland, Norway, and Sweden until 2 years of age. Rates of infectious disease hospitalisations with minimum one overnight stay according to time-varying vaccination status were compared using Cox proportional hazards regression analysis with age as the underlying timescale and including multiple covariates. Summary estimates were calculated using random-effects meta-analysis. Compared with DTaP3 and no MMR vaccine, MMR after DTaP3 was associated with reduced rates of infectious disease hospitalisations: aHR was 0.86 (0.83-0.89) in Denmark, 0.70 (0.64-0.75) in Finland, 0.71 (0.68-0.74) in Norway, and 0.71 (0.65-0.77) in Sweden: summary estimate was 0.75 (0.65 to 0.84). A beneficial association was also seen in a negative control exposure analysis (3 vs. 2 DTaP doses): summary estimate aHR was 0.81 (0.75-0.87). Having MMR as the most recent vaccine was consistently associated with reduced rated of infectious disease hospitalization. However, bias may account for at least some of the observed association. Randomised controlled trials are warranted to inform the optimal timing of MMR for both its specific and potential non-specific effects.

The Causes, Characteristics and Outcomes of Paediatric Farm Burns in Australia and New Zealand.

Burn injuries on farms are under-recognised in Australia and New Zealand. Previous studies suggested children are at risk of burn injury, focusing on risk factors including unmodified farm work, risk-taking behaviours, lack of supervision, and limited safety regulations. This study investigated the causes, characteristics, and outcomes of paediatric farm burns. Registry-based retrospective cohort study. Observational. Burns Registry of Australia and New Zealand (BRANZ). Paediatrics aged < 16 years and registered to the BRANZ between 2009 and 2021. The demographics, causes of burn injuries, pre- and in-hospital management, severity, and outcomes. Out of 10 936 paediatric burns, 186 were farm-related (1.7%). Children sustaining farm-related burns were older than those in non-farm environments, with 78.8% aged ≥ 5 years. Most farm burns occurred during leisure (72.5%). Predominant causes were found to be contact (62.4%), followed by flame (19.9%) and friction (10.8%). Only 56.9% received gold-standard first aid compared to 74.0% in non-farm environments. Farm-related burns were smaller but a greater proportion were full-thickness injuries, requiring surgical management with skin grafts. The majority of farm-related burns were discharged home (97.3%) with zero deaths. Farm-related burns in children are distinct from burns in non-farm environments. Despite children being well-recognised participants in farm work, work-related burns were relatively uncommon, and the occurrence of burns during leisure may explain low rates of recommended first aid. These insights can inform burn prevention and first aid strategies targeted at farm communities.

Intraoperative FiO2 and risk of impaired postoperative oxygenation in lung resection: A propensity score-weighted analysis.

To assess whether, in a lung resection cohort with a low probability of confounding by indication, higher FiO2 is associated with an increased risk of impaired postoperative oxygenation - a clinical manifestation of lung injury/dysfunction. Pre-specified registry-based retrospective cohort study. Two large academic hospitals in the United States. 2936 lung resection patients with an overall good intraoperative oxygenation (median intraoperative SpO2≥95%). We compared patients with a higher (≥0.8) and lower (<0.8) median intraoperative FiO2 after propensity score-weighting for 75 perioperative variables based on a causal inference framework. The primary outcome of impaired oxygenation was defined as at least one of the following within seven postoperative days: (1) SpO2<92%; (2) imputed PaO2/FiO2<300mmHg [(1) or (2) at least twice within 24h]; (3) intensive oxygen therapy (mechanical ventilation or>50% oxygen or high-flow oxygen). Among the 2936 included patients, 2171 (73.8%) received median intraoperative FiO2≥0.8. Impaired postoperative oxygenation occurred in 1627 (74.9%) and 422 (55.2%) patients in the higher and lower FiO2 groups, respectively. In a propensity score-weighted analysis, higher intraoperative FiO2 was associated with an 84% increase in the likelihood of impaired postoperative oxygenation (OR 1.84; 95% CI 1.60 to 2.12; P<0.001). Despite plausible harm from hyperoxia, high intraoperative FiO2 is extremely common during lung resection. Nearly three-quarters of lung resection patients with acceptable oxygenation received median intraoperative FiO2≥0.8. Such higher FiO2 was associated with an increased risk of impaired postoperative oxygenation - a clinically relevant manifestation of lung injury or dysfunction. This observation supports the administration of a lower (< 0.8) intraoperative FiO2 and its further assessment in clinical trials.

Major regional differences in the use of labor analgesia in Finland – A national register study

IntroductionLabor analgesia should be equally available to every woman giving birth. However, previous studies have found notable regional differences between countries and regions in the use of epidural analgesia. We aim to evaluate the trends in the use of different labor analgesia methods in Finnish hospital districts. Material and methodsWe performed a nationwide retrospective register-based cohort study. From January 1, 2007 to December 31, 2019, we collected vaginal birth data concerning used labor analgesia from the national Finnish Medical Birth Register. Cesarean sections were excluded because of the missing labor analgesia data from the elective operations. Data were grouped and interpreted based on 19 hospital districts in Finland. ResultsThere were 567 593 vaginal births during the years 2007–2019. Major differences were observed in the use of labor analgesia between hospital districts. The trends also varied during the study period within the same hospital district. Neuraxial analgesia was the most used during the study period – on average 63.6 % of the deliveries had neuraxial analgesia. It was followed by nitrous oxide by 58.0 %. Interestingly, the rates of non-pharmaceutical analgesia increased the most during the study period. ConclusionsThe results showed major differences in the use of different labor analgesia methods between Finnish hospital districts, and the analgesia policies do not seem to be nationwide.

Reduced healthcare costs for patients with screen-detected colorectal cancer: A Danish nationwide cohort study.

This Danish nationwide retrospective register-based cohort study investigated healthcare costs for patients with screen-detected colorectal cancer (SD-CRC) compared to non-screen-detected CRC (NSD-CRC). Nationwide cohort study. Quarterly healthcare costs including costs of hospital care, out-of-hospital medication, and primary sector contacts were compared between the two groups from two years before diagnosis of CRC until two years after. A quasi-experimental difference-in-differences analysis was performed to estimate the differences per patient in total quarterly healthcare costs between the groups. A total of 13,852 patients were included, 4703 with SD-CRC, 7420 with NSD-CRC, and 1,729 with interval- or post-colonoscopy CRC (I-PC-CRC). The total quarterly healthcare costs per patient were significantly higher in the NSD-CRC group than in SD-CRC. This was consistent across the total period and in 6-month analyses, accruing additional €16,600 of costs for patients with NSD-CRC over two years after diagnosis. Total healthcare costs were significantly higher for patients with NSD-CRC as compared to patients with SD-CRC across all Union for International Cancer Control (UICC) stages, except for UICC stage I. Correspondingly, total costs associated with I-PC-CRC were significantly higher than for SD-CRC. Apart from improving post-treatment outcomes, higher participation rates in the CRC screening programmes present an opportunity for reducing healthcare costs related to patients diagnosed with CRC.

Risk of Epilepsy Following a First Posttraumatic Seizure: A Register-Based Study.

Traumatic brain injury (TBI) is a common cause of epilepsy, and the risk increases with injury severity. Whether a first posttraumatic seizure (PTS) represents epilepsy is a common clinical problem, but often unknown. Prognostication is important for providing correct patient information and consideration of antiseizure medication. Our objective was to understand how trauma severity and latency from the injury affect the risk of epilepsy after a first PTS. The register-based cohort study including all individuals hospitalized following a TBI in Sweden 2000-2010, in addition to 3 age-matched and sex-matched controls per case. We analyzed the 10-year probability of epilepsy following a first seizure using the Kaplan-Meier estimator. The risk of an epilepsy diagnosis was 41.1% (95% CI 38.6-43.7) following a PTS, higher than the risk of 33.4% (95% CI 30.3-36.5) in those without prior TBI. The risk increased with injury severity, with the highest risk following focal cerebral injuries, 62.3% (95% CI 53.7-70.9). Mild injuries and skull fractures showed a similar risk to the group without previous TBI. In addition, the risk was higher if the seizure occurred <2 years following the trauma. Severity of the injury and latency are major modulators of epilepsy risk following a first PTS. The risk was high in the most severe types of TBI, but a substantial proportion did not develop epilepsy, highlighting the need for further research on prognostication and biomarkers, as well as caution in diagnosing epilepsy based on a first PTS.

Employment before and after initiation of dialysis or kidney transplantation- a Danish nationwide registry-based cohort study.

Patients treated with chronic dialysis or kidney transplantation have difficulties in maintaining employment. We aimed to estimate employment rates among dialysis and kidney transplant patients from 3 years before to 3 years after initiating dialysis or undergoing transplantation. All first-time dialysis and kidney transplantation patients aged 18-65 years in Denmark from 2005 to 2019 were identified using the Danish Nephrological Register and linked with information about social security benefits. Each dialysis or kidney transplant patient was matched with 3 references. In total, 4,469 patients undergoing dialysis (median age 55 years, 65% males) and 2,294 patients receiving kidney transplants (median age 49 years, 64% males) were included together with 13,262 and 6,790 matched references, respectively. The employment rate was 11% when initiating dialysis compared to 61% for the reference group. Kidney transplantation patients had an employment rate of 20% compared to 67% for the reference group. At all time points (3 years before, 1 year before, at the time of intervention, 1 year after, and 3 years after) both dialysis and kidney transplant patients had lower employment rates compared to references (P < 0.001). There was only a partial return to work after transplantation. Employment rates increased in ESKD patients in the period 2005-2019, however, the increase was not different from corresponding reference groups. Employment rates in ESKD patients are very low and decline long before initiation of dialysis or kidney transplantation. Of concern, kidney transplantation only leads to a small increase in employment. There has been no improvement in the employment of ESKD patients from the period 2005-2009 to 2015-2019.

Previous surgery for lumbar spinal stenosis and association with amyloidosis and heart failure – A Danish nationwide study

Introduction Cardiac Amyloidosis (CA) is characterised by amyloid fibril deposits causing heart failure (HF). Lumbar spinal stenosis (LSS) is recognised as a potential red flag for CA, but the association remains underexplored in large-scale studies. Methods This nationwide registry-based cohort study in Denmark included subjects ≥60 years with a history of LSS surgery. LSS patients were matched 1:1 with controls by age, sex, ischaemic heart disease, chronic obstructive lung disease, chronic kidney disease, diabetes, and atrial fibrillation. Results A total of 44,548 LSS surgery patients and matched controls were included (median age 71.5 years, 56.2% women). The cumulative incidence of amyloidosis after 10 years was higher in the LSS group (0.16% vs. 0.08%, HR 2.29 [95% CI 1.46–3.60]) after adjustment for malignancy, hypertension, and liver disease. The cumulative incidence of HF after 10 years was 10.1% in LSS patients compared with 7.5% in controls (HR 1.28 [95% CI 1.22–1.35], p < 0.0001). Conclusions In this nationwide cohort study, LSS surgery was associated with a significantly higher risk of amyloidosis and HF. Prospective studies are warranted to explore the association further.

Effects of femoral neck width and hip Axis length on incident hip fracture risk: a registry-based cohort study.

Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) is widely used in clinical practice to assess fracture risk and guide management. DXA can also assess hip geometry, including femoral neck width (FNW) and hip axis length (HAL), which have both been associated with increased risk for hip fracture independently from BMD. Our objective was to assess if FNW predicts hip fracture independently from other factors including HAL. We performed a retrospective cohort study using the Province of Manitoba BMD registry. The study population comprised 75 095 individuals (90.8% women), mean age 64.7years, with baseline hip BMD and hip geometry parameters. Linked health records were used to ascertain subsequent hospitalization with hip fracture as a primary diagnosis. During a mean follow up of 8.3 (SD 5.1) years, 2341 incident hip fractures were recorded. Each SD increase in age- and sex-adjusted FNW was associated with incident hip fracture (HR 1.15, 95% CI 1.10-1.19) which was unchanged after adjustment for height, weight, femoral neck BMD and clinical risk factors. However, FNW showed a significant positive correlation with HAL (r = 0.68). When further adjusted for HAL, FNW was no longer associated with increased risk for hip fracture (HR 0.98, 95% CI 0.94-1.03). A similar pattern was seen for femoral neck, intertrochanteric and non hip fractures. In contrast, increased risk of hip fracture was consistently seen with each SD increase in HAL even after adjustment for all covariates including FNW (HR 1.35, 95% CI 1.28-1.42). In conclusion, FNW is a risk factor for hip fracture before but not after adjustment for HAL. HAL, on the other hand, robustly and independently predicts hip fracture, including both femoral neck and trochanteric fractures.

Secondary Resections and Survival After Breast-Conserving Surgery in Breast Cancer Patients: A Cancer Registry-Based Cohort Study

Secondary Resections and Survival After Breast-Conserving Surgery in Breast Cancer Patients: A Cancer Registry-Based Cohort Study

Fear of childbirth and psychiatric disorders decrease the likelihood of subsequent births: a retrospective register-based cohort study

BackgroundMirroring other developed countries globally, the birth rate has decreased in Finland in recent years. The effects of a fear of childbirth (FOC) and psychiatric disorders on the likelihood of having more than one child remain relatively unstudied. This study aims to assess the influence of FOC, psychiatric disorders, and the mode of first delivery on the likelihood of the second birth among primiparous women.MethodsData were collected from the Medical Birth Register, the Hospital Discharge Register, and Statistics Finland census data. We used the t-test to compare continuous variables and the chi-square test or test for relative proportions to compare categorical variables. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) using the Cox regression analysis.ResultsAltogether, 317 219 women delivering their first child in 2006–2016 met the inclusion criteria, 216 521 of whom (68.3%) had their second birth during that time. A total of 11 108 (3.5%) of women were diagnosed with FOC during their first pregnancy, 34 381 (10.8%) women were diagnosed with a psychiatric disorder before or during their first pregnancy and 10 331 (3.3%) women received a new diagnosis of a psychiatric condition following the first birth. Between 2006–2021, the second child was born to 47.5% of women with FOC (n = 5276), 56.8% of women with a psychiatric disorder before or during their first pregnancy (n = 19 540), 53.4% of women receiving a psychiatric diagnosis after their first delivery (n = 5514) and 70.2% of women without either of these diagnoses (n = 191 572). Women with FOC had a 22% lower likelihood of the second birth [aHR 0.78 (95% CI 0.76–0.80)] compared to women without FOC. A psychiatric disorder before or during the first pregnancy decreased the likelihood of the second birth by 28% [aHR 0.72 (95% CI 0.71–0.73)] and by 51% (aHR 0.49 (95% CI 0.48–0.50)] with a psychiatric disorder following a first birth compared with women without a diagnosed psychiatric disorder. Among all women, a caesarean section as the mode of a first delivery reduced the likelihood of the second birth.ConclusionFOC and psychiatric disorders are associated with a low birthrate following the first delivery. Caesarean section as the mode of delivery decreases the likelihood of the second birth among women with FOC and psychiatric disorders.

P1206 The Incidence and Disease Course of Perianal Disease in Paediatric-Onset Crohn's Disease: A Danish Nationwide Cohort Study Covering 1980-2022

Abstract Background Perianal Crohn's disease (CD) is characterised by fistulae and/or abscesses in the anal region and leads to significant morbidity. We aimed to estimate the incidence and describe the disease course of perianal disease in paediatric-onset CD patients (&amp;lt;18 years at CD diagnosis). Methods In a nationwide registry-based cohort study, we identified all incident patients with paediatric-onset CD in Denmark from 1980 to 2018. We followed the patients until emigration, death, or December 31, 2022, and recorded the cumulative incidence of perianal disease based on data from the National Patient Registry. Using perianal disease as an exposure, we further assessed the risks of major abdominal surgeries, colorectal and anal cancer, and mortality. We used multivariate Cox regression analysis with biological age as the timescale to estimate hazard ratios adjusted (aHR) for sex, family income, and calendar year of CD diagnosis. Results We identified 2,356 paediatric-onset CD patients, of whom 769 (32.6%) were diagnosed with perianal CD. Total follow-up time was 38,584 person-years. The cohort is described in detail in Table 1. The cumulative incidence of perianal CD was 14.0%, 21.1%, and 28.1% after 1, 5, and 10 years after CD diagnosis, respectively. The incidence density during the study period was 29 (95% confidence interval [CI]: 26.8–30.9) per 1,000 person-years, corresponding to 45.2% after 30 years of follow-up. Among the 769 patients with perianal CD, 460 (59.8%) had perianal abscesses, 399 (51.9%) perianal fistula, and 627 (81.5%) patients underwent perianal surgery. Of CD patients with perianal disease, 308 (40.1%) required a stoma compared to 147 (9.3%) of patients without, corresponding to an aHR of 2.8 (95% CI: 2.3-3.4). When comparing CD patients with perianal disease to those without, the aHRs for major abdominal surgery, cancer, and mortality were 1.5 (95%CI: 1.3–1.8), 0.8 (95% CI: 0.2–2.7), and 1.5 (95%CI: 0.9–2.7), respectively. Of the 68 patients that died, 35 (2.2/1,000 person-years) had perianal disease, whereas 33 (1.4/1,000 person-years) had not. Further risk analysis is presented in Figure 1. Conclusion In this nationwide cohort of patients with paediatric-onset CD (&amp;lt;18 years at CD diagnosis), 29 patients per 1,000 person-years developed perianal disease between 1980-2022. Patients with perianal CD were more likely to require major abdominal surgery, including stoma surgery, and had a higher risk of mortality compared to patients without perianal CD. Our study underlines the severity of perianal disease in paediatric-onset CD.

Montelukast Use and the Risk of Neuropsychiatric Adverse Events in Children

Spontaneous reports have indicated that montelukast increases the risk of neuropsychiatric adverse events, and the US Food and Drug Administration added a boxed warning about these risks in 2020. However, the potential mechanism is not well understood, and the observational evidence is scarce, particularly in children. To assess the potential association between the use of montelukast and the risk of neuropsychiatric adverse events in children and adolescents. This nationwide register-based cohort study used data from Sweden from January 1, 2007, to November 30, 2021. Participants included children aged 6 to 17 years who used montelukast and long-acting β-agonists (LABA). Data analysis was performed from December 2023 to April 2024. Montelukast vs LABA. The primary outcome, any neuropsychiatric adverse event, was a composite of secondary outcomes, including anxiety; depression; sleep-related disorders; suicide and suicidal actions; disrupted control of activity, attention, and behavior; and confusion and psychotic-like symptoms. Outcomes were defined on the basis of diagnosis codes and dispensings of prescription drugs for specific neuropsychiatric symptoms. Patients were followed up from drug initiation to discontinuation, and treatment and censoring weights were used to adjust for potential confounding on baseline and selection bias from informative censoring. Pooled logistic regression was used to estimate hazard ratios (HRs). The final cohort included 74 291 children (mean [SD] age, 12.3 [3.3] years; 35 446 female [47.7%]); 26 462 used montelukast and 47 829 used LABA. During a mean (SD) follow-up of 5.8 (3.2) months, 310 neuropsychiatric adverse events in the montelukast patients and 566 events in the LABA patients were identified. In the weighted cohort, the incidence rates of neuropsychiatric adverse events were 2.39 per 100 patient-years among the montelukast users and 2.41 per 100 patient-years among the LABA users. This translated to a weighted HR of 0.99 (95% CI, 0.84-1.16). No substantial differences were observed between the montelukast and LABA patients when analyzing the risk of specific neuropsychiatric adverse events: the HRs were 0.79 (95% CI, 0.54-1.14) for anxiety; 1.16 (95% CI, 0.70-1.95) for depression; 0.93 (95% CI, 0.76-1.13) for sleep-related disorders; 1.31 (95% CI, 0.64-2.69) for suicide and suicidal actions; 1.27 (95% CI, 0.84-1.90) for disrupted control of activity, attention, and behavior; and 0.51 (95% CI, 0.05-5.53) for confusion and psychotic-like symptoms. The risk of the primary outcome was consistent over subgroups and a range of sensitivity analyses. In this large study of children and adolescents based on data from routine clinical practice, there was no association between use of montelukast and the risk of neuropsychiatric adverse events. In aggregation with other robust observational studies, these results can inform the management of asthma and allergic rhinitis in this patient group.

Healthcare use in 12-18-year-old adolescents vaccinated against SARS-CoV-2 versus unvaccinated in a national register-based Danish cohort.

Healthcare use among adolescents after vaccination against SARS-CoV-2 is unknown. In a real-life register-based cohort study (trial NCT04786353), healthcare use was compared among Pfizer-BioNTech BNT162b2 COVID-19 vaccinated and unvaccinated 12-18-year-olds. First-dose-vaccinated (between 1 May and 30 September 2021) adolescents were sex and age matched 1:1 with unvaccinated adolescents. Outcomes were visits to emergency rooms, hospitalization, and visits to general practitioners and specialist practitioners. The prior event rate ratio (PERR) was applied. The study finds that boys had fewer visits to general practitioners (PERR 0.93, 95% confidence interval (CI) 0.89-0.99) after the first vaccine. Up to 56 days after the second dose, vaccinated boys had lower rates of visits to specialist practitioners (0.88, 95% CI 0.79-0.99); after 57-182 days, vaccinated girls and boys had higher rates of visits to emergency rooms (1.22, 95% CI 1.08-1.39; 1.17, 95% CI 1.07-1.31) and to general practitioners (1.17, 95% CI 1.12-1.21; 1.17, 95% CI 1.13-1.22). Furthermore, vaccinated boys had higher rates of visits to specialist practitioners (1.23, 95% CI 1.08-1.39). Estimates were close to one and do not indicate that BNT162b2 leads to a practically meaningful increase in healthcare use among vaccinated adolescents.

The impact of palliative care contact on the use of hospital resources at the end of life for brain tumor patients; a nationwide register-based cohort study.

The aim of this nationwide retrospective cohort study was to evaluate the timing of the first specialist palliative care (SPC) contact and its impact on the use of hospital resources at the end of life in patients with brain tumors. The analysis comprised 373 brain tumor patients who died during 2019 in Finland. Patients were divided into two groups according to the time of first SPC contact: early, i.e. first SPC contact more than 30 days before death, and late, i.e. no SPC contact or 30 days or less before death. 216 (58%) were male, with a mean age of 67 years (range 18-94). SPC contact was established for 102 (27%) patients and the median time of first SPC contact before death was 76 days. Patients with an early SPC contact had fewer outpatient clinic contacts (28% vs. 53%; p-value < 0.001) and fewer hospitalization (10% vs. 37%; p-value < 0.001) in secondary care compared with patients with late SPC contact. Early SPC contact had no impact on emergency department contacts. Patients with early SPC contact were more likely to die at long term care facility or in SPC wards instead of hospital (p-value < 0.001) compared to patients with late SPC contact (hospital deaths 51% vs. 80%, respectively). Early SPC contact reduced the burden on secondary care for brain tumor patients in the last months of life. Palliative care contact should be offered early to all brain tumor patients.

Occupational exposure to diesel engine exhaust and first-time acute myocardial infarction - a nationwide register-based cohort study 1976- 2018.

Exposure to air pollution including diesel engine exhaust (DEE) is associated with increased risk of acute myocardial infarction (AMI). Few studies have investigated the risk of AMI according to occupational exposure to DEE. The aim of this study was to evaluate the association between occupational exposure to DEE and the risk of first-time AMI. The study was a register-based cohort study of the Danish working population and included 903,415 individuals aged 35-50 years in 1995. Exposure estimates of DEE were assigned by linking a quantitative DEE job exposure matrix with the individual job history (1976-2017). National registers provided data on AMI throughout the follow-up period (1996-2018). The incidence rate ratios (IRR) for AMI were computed using Poisson regression while adjusting for demographics, comorbidities, socio-economic factors, ambient air pollution and occupational exposure to noise, physically demanding work, and job strain. 35,511 cases of AMI occurred during the follow-up period of 19,357,326 person-years. IRRs for cumulative exposure to DEE in the fully adjusted model were 1.04 (95%CI: 1.00-1.08) for exposure levels between the 50th and 75thpercentiles and 1.08 (95%CI: 1.04-1.12) for exposure levels ≥75thpercentile. Recent exposure to DEE was associated with an increased IRR in the highest exposed quartile (IRR=1.15 (95%CI: 1.05-1.27)), but only when compared within exposed workers. Increasing exposure to DEE was associated with increasing IRR for first-time AMI across different exposure measures. The results indicate that AMI should be included in risk assessment of DEE when establishing occupational exposure limits.