Abstract Pediatric health service differs between and within countries. To prioritize limited resources, data-driven studies on pediatric tertiary hospital contacts are warranted. This ...population-based register study identified all contacts with four Danish tertiary hospitals 2000–2018 by 0–17-year-old patients. During 2000–2018, 2,496,001 individuals resided in Denmark while 0–17 years old, and the study described 829,562 inpatient and 3,932,744 outpatient contacts at tertiary hospitals by hospital, sex, age, diagnosis, department, and residence. Male patients accounted for more contacts overall (inpatient 55.51%, outpatient 52.40%) and more contacts with severe chronic disease (inpatient 56.24%, outpatient 54.41%). Median (interquartile range) patient age was 3.09 (0.26–9.96) and 8.48 (2.78–13.70) years for in- and outpatient contacts. Overall, 28.23% and 21.02% of in- and outpatient contacts included a diagnosis of a severe chronic disease, but the proportions differed across hospitals. A pattern of pediatric healthcare directed towards less severe diseases was observed: While the total number of outpatient visits at tertiary hospitals increased from 2000 to 2018, the proportion of these contacts which had a diagnosis of a severe chronic disease decreased. Future comparisons between hospitals regarding pediatric outcomes should consider potential differences in terms of uptake and diagnosis severity. Such findings may have implications for future pediatric organization, nationally and internationally.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of ...broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery.
A Danish nationwide cohort study including all singletons born during 1997-2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes.
Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation.
Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients receiving total hip arthroplasty (THA) due to metastatic bone disease of the hip (MBD) are at an increased risk of post-operative joint dislocation compared to other populations. Different ...joint solutions have been developed with the purpose of reducing the dislocation risk compared to regular THAs. One of these solutions, the constrained liner (CL), has been used increasingly at our department in recent years. This design, however, is prone to polyethylene wear and higher revision rates. An alternative is the dual mobility cup (DM), which has been shown to reduce the risk of dislocation in other high-risk populations. Few studies have investigated DM for THA due to MBD, and no studies have directly compared these two treatments in this population. We therefore decided to conduct a trial to investigate whether DM is non-inferior to CL regarding the post-operative joint dislocation risk in patients receiving THA due to MBD.
This study is a single-center, randomized, open-label, two-arm, non-inferiority trial. We will include 146 patients with MBD of the hip who are planned for THA at the Department of Orthopedic Surgery, Rigshospitalet. Patients with previous osteosynthesis or endoprosthetic surgery of the afflicted hip, or who are planned to receive partial pelvic reconstruction or total femoral replacement, will be excluded. Patients will be stratified by whether subtrochanteric bone resection will be performed and allocated to either CL or DM in a 1:1 ratio. The primary outcome is the 6 months post-operative joint dislocation rate. Secondary outcomes include overall survival, implant survival, the rate of other surgical- and post-operative complications, and quality of life and functional outcome scores.
This study is designed to investigate whether DM is non-inferior to CL regarding the risk of post-operative dislocation in patients receiving THA due to MBD. To our knowledge, this trial is the first of its kind. Knowledge gained from this trial will help guide surgeons in choosing a joint solution that minimizes the risk of dislocation and, ultimately, reduces the need for repeat surgeries in this patient population.
ClinicalTrials.gov Identifier: NCT05461313. Registered on July 15 2022. This trial is reported according to the items in the WHO Trial Registration Data Set (Version 1.3.1).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional ...mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12–2.31, p = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15–2.21, p = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02–1.11. p = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Adult overweight is a potential bladder cancer (BC) risk factor, but little is known about size earlier in life.
Aim: To investigate if birth weight, childhood body mass index (BMI), ...height and growth are associated with adult BC.
Subjects and methods: Anthropometric information from birth and ages 7-13 on 315,763 individuals born 1930-1989 in the Copenhagen School Health Records Register was linked to national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression.
Results: 1145 individuals (839 men) were diagnosed with BC. Sex differences were not detected. Childhood BMI had positive associations and height had inverse associations with BC; at age 13, HR = 1.10 (95% CI: 1.02-1.18) per BMI z-score and HR = 0.94 (95% CI: 0.89-1.00) per height z-score. A pattern of above-average increases in BMI from 7 to 13 years had higher hazards of BC than average increases. Above-average growth in height was not significantly associated with BC. Compared with birth weights of 3.5 kg, low (2.5 kg) and high (4.5 kg) values were associated with increased hazards of BC; HR = 1.26 (95% CI: 1.01-1.58) and HR = 1.36 (95% CI: 1.09-1.70), respectively.
Conclusions: A high BMI, a short height, excess BMI gain in childhood and low and high birth weights are associated with increased hazards of BC.
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DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidemiological studies of related individuals are often complicated by the fact that follow-up on the event type of interest is incomplete due to the occurrence of other events. We suggest a class ...of frailty models with cause-specific hazards for correlated competing events in related individuals. The frailties are based on sums of gamma distributed variables and offer closed form expressions for the observed intensities. An inference procedure with a recursive baseline estimator is proposed, and its large sample properties are established. The estimator readily handles cluster left-truncation as occurring in the Nordic twin registers. The performance in finite samples is investigated by simulations and an example on prostate cancer in twins is provided for illustration.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, INZLJ, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK, ZRSKP
•A 17% reduction in hospital admissions of non-opioid analgesic poisonings was observed after an age restriction was applied to sales of over-the-counter drugs among 10–17-year old in Denmark.•An ...instant 18.5% reduction of non-opioid analgesics poisonings was seen after implementation of a pack size restriction.•Other pharmaceutical poisonings also decreased during the study period.•Measures of serious hepatic injury decreased by 27% and 40%, respectively, following the pack size restriction.•Although declines in poisonings were observed after implementation of means restrictive measures, a causal link cannot be inferred.•We cannot exclude the possibliity of confounding through general societal changes.
Self-poisoning with non-opioid analgesics presents a growing challenge to health care providers. We aimed to assess the impact of an 18-year age restriction of OTC sales and a pack size restriction of non-opioid analgesics sold OTC in pharmacies on hospital-treated poisonings and poisoning severity measured using biomarkers.
We applied a before and after design using interrupted time series analysis. Data on all poisonings recorded as hospital admissions were obtained during 2002–2015 and biochemical parameters from laboratory databases during 2011–2015, both covering the entire Danish population.
The age restriction was followed by a 17% level reduction in admissions for non-opioid analgesic poisoning among young people age 10–17 years (RR 0.830; 95% CI 0.697–0.988; p < 0.036). After the pack size restriction, an instant level reduction of 18.5% (RR 0.815; 95% CI 0.729–0.912; p < 0.001) was observed for the entire population. A 27% decrease in the number of poisonings with alanine transaminase levels (ALT) ≥ 210 U/L was observed (RR 0.734; 95% CI 0.579–0.931; p = 0.011) followed by 40% decrease in biomarkers indicative of liver failure (RR 0.597; 95% CI 0.421–0.847; p = 0.004). We also observed similar reductions for other poisonings such as psychotropics.
Although declines in poisonings were observed after implementation of means restrictive measures, a causal link cannot be inferred.
Age and pack size restriction were assiociated with a reduction in the numbers of poisonings. This was also observed for pharmaceutical poisonings in general, which might suggest a non-specific or spill-over effect.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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