Harmonization of epidemiology of acute kidney injury and acute kidney disease produces comparable findings across four geographic populations

Acknowledgements: We acknowledge the support of the Grampian Data Safe Haven (DaSH) facility within the Aberdeen Centre for Health Data Science and the associated financial support of the University of Aberdeen, and NHS Research Scotland (through NHS Grampian investment in DaSH). For more information, visit the DaSH website: http://www.abdn.ac.uk/iahs/facilities/grampian-data-safe-haven.php Dr Sawhney is supported by a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences, Wellcome Trust, Medical Research Council, British Heart Foundation, Arthritis Research UK, the Royal College of Physicians and Diabetes UK [SGL020\1076]. Drs James and Tonelli are supported by Canadian Institutes of Health Research Foundation Grants. Dr Black is supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust.Peer reviewedPublisher PD

Recovery of Kidney Function After Acute Kidney Disease - a Multi-Cohort Analysis

Background: There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark, and Scotland, 2011-2018.Methods: We identified incident AKD defined by serum creatinine changes within 48 hours, 7 days, and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2x baseline. We evaluated transitions between non-recovery, recovery, and death up to one year; within age, sex, and comorbidity subgroups; between subset AKD definitions; and across cohorts.Results: There were 464,868 incident cases, median ages 67-75 years. At one year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 hours, 7 days, 90 days and 365 days (and 95% CI) of 40% (34-45%), 40% (34-46%), 37% (31-42%), 22% (16-29%) respectively; and non-recovery of kidney function of 19% (15-23%), 30% (24-35%), 25% (21-29%), 37% (30-43%) respectively. Recovery by 14 and 90 days was frequently not sustained at one year. Older males and those with heart failure or cancer were more likely to die than experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes.Conclusion: Consistently across multiple cohorts, based on one-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover

Birth and Neonatal Outcomes following Opioid Use in Pregnancy: A Danish Population-Based Study

Background Few population-based data exist on birth outcomes in women who received opioid maintenance treatment during pregnancy. We therefore examined adverse birth outcomes in women exposed to methadone or buprenorphine during pregnancy and the risk of neonatal abstinence syndrome (NAS) among neonates exposed to buprenorphine, methadone, and/or heroin in utero. Patients and Methods This study included all female Danish residents with a live birth or a stillbirth from 1997 to 211. We identified the study population, use of opioids and opioid substitution treatment, birth outcomes, and NAS through medical registers. Birth outcomes included preterm birth (born before 38th gestational week), low-birth weight (LBW) (<2,500 g, restricted to term births), small for gestational age (SGA) (weight <2 standard deviations from the sex- and gestational-week-specific mean), congenital malformations, and stillbirths. We used log-binomial regression to estimate the prevalence ratio (PR) for birth outcomes. Results Among 95,172 pregnancies in a total of 571,823 women, we identified 557 pregnancies exposed to buprenorphine, methadone, and/or heroin (167 to buprenorphine, 197 to methadone, 28 to self-reported heroin, and 165 to combinations). Compared with nonexposed pregnancies, prenatal opioid use was associated with greater prevalence of preterm birth (PR of 2.8 (95% confidence interval (CI), 2.3–3.4)), LBW among infants born at term (PR of 4.3 (95% CI, 3.0–6.1)), and being SGA (PR of 2.7 (95% CI, 1.9–4.3)). Restricting the analyses to women who smoked slightly lowered these estimates. The prevalence of congenital malformations was 8.3% in opioid-exposed women compared with 4.2% in nonexposed women (PR of 2.0 (95% CI, 1.5–2.6)). The risk of NAS ranged from 7% in neonates exposed to buprenorphine only to 55% in neonates exposed to methadone only or to opioid combinations. Conclusion The maternal use of buprenorphine and methadone during pregnancy was associated with increased prevalence of adverse birth outcomes, and this increase could only be explained to a smaller extent by increased prevalence of smoking. The risk of NAS was eight-fold higher in methadone-exposed neonates than that in buprenorphine-exposed neonates, but this difference may at least partly be explained by differences in underlying indications (analgesic versus opioid maintenance treatment) between the two groups

Mammographic density is a potential predictive marker of pathological response after neoadjuvant chemotherapy in breast cancer

BACKGROUND: Our aim is to study if mammographic density (MD) prior to neoadjuvant chemotherapy is a predictive factor in accomplishing a pathological complete response (pCR) in neoadjuvant-treated breast cancer patients.METHODS: Data on all neoadjuvant treated breast cancer patients in Southern Sweden (2005-2016) were retrospectively identified, with patient and tumor characteristics retrieved from their medical charts. Diagnostic mammograms were used to evaluate and score MD as categorized by breast composition with the Breast Imaging-Reporting and Data System (BI-RADS) 5th edition. Logistic regression was used in complete cases to assess the odds ratios (OR) for pCR compared to BI-RADS categories (a vs b-d), adjusting for patient and pre-treatment tumor characteristics.RESULTS: A total of 302 patients were included in the study population, of which 57 (18.9%) patients accomplished pCR following neoadjuvant chemotherapy. The number of patients in the BI-RADS category a, b, c, and d were separately 16, 120, 140, and 26, respectively. In comparison to patients with BI-RADS breast composition a, patients with denser breasts had a lower OR of accomplishing pCR: BI-RADS b 0.32 (95%CI 0.07-0.1.5), BI-RADS c 0.30 (95%CI 0.06-1.45), and BI-RADS d 0.06 (95%CI 0.01-0.56). These associations were measured with lower point estimates, but wider confidence interval, in premenopausal patients; OR of accomplishing pCR for BI-RADS d in comparison to BI-RADS a: 0.03 (95%CI 0.00-0.76).CONCLUSIONS: The likelihood of accomplishing pCR is indicated to be lower in breast cancer patients with higher MD, which need to be analysed in future studies for improved clinical decision-making regarding neoadjuvant treatment

Neoadjuvant breast cancer treatment response; tumor size evaluation through different conventional imaging modalities in the NeoDense study

Neoadjuvant chemotherapy (NACT) is offered to an increasing number of breast cancer (BC) patients, and comprehensive monitoring of treatment response is of utmost importance. Several imaging modalities are available to follow tumor response, although likely to provide different clinical information. We aimed to examine the association between early radiological response by three conventional imaging modalities and pathological complete response (pCR). Further, we investigated the agreement between these modalities pre-, during, and post-NACT, and the accuracy of predicting pathological residual tumor burden by these imaging modalities post-NACT

Associations between physical diseases and subsequent mental disorders

This project provides the pre-registered analysis plan and supplementary material of our study published in World Psychiatry: Momen NC, Østergaard SD, Heide-Jorgensen U, Sørensen HT, McGrath JJ, Plana-Ripoll O. Association between physical diseases and subsequent mental disorders: a longitudinal study in a population-based cohort. World Psychiatry. 2024; xx (xx): xx-xx

Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

Purpose: Personalized cancer treatment requires predictive biomarkers, including image-based biomarkers. Breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT) are in a clinically vulnerable situation with the tumor present. This study investigated whether mammographic density (MD), assessed pre-NACT, is predictive of pathological complete response (pCR). Methods: A total of 495 BC patients receiving NACT in Sweden 2005–2019 were included, merged from two different cohorts. Cohort 1 was retrospectively collected (n = 295) and cohort 2 was prospectively collected (n = 200). Mammograms were scored for MD pre-NACT according to the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. The association between MD and accomplishing pCR post-NACT was analyzed using logistic regression models—for the whole cohort, stratified by menopausal status, and in different St. Gallen surrogate subtypes. Results: In comparison to patients with low MD (BI-RADS a), the multivariable-adjusted odds ratio (OR) of accomplishing pCR following NACT was on a descending scale: 0.62 (95% confidence interval (CI) 0.24–1.57), 0.38 (95% CI 0.14–1.02), and 0.32 (95% CI 0.09–1.08) for BI-RADS b, c, and d, respectively. For premenopausal patients selectively, the corresponding point estimates were lower, although wider CIs: 0.31 (95% CI 0.06–1.62), 0.24 (95% CI 0.04–1.27), and 0.13 (95% CI 0.02–0.88). Subgroup analyses based on BC subtypes resulted in imprecise estimates, i.e., wide CIs. Conclusions: It seemed as though patients with higher MD at baseline were less likely to reach pCR after NACT—a finding more pronounced in premenopausal women. Larger multicenter studies are needed to enable analyses and interpretation for different BC subtypes

Mammographic density changes during neoadjuvant breast cancer treatment : NeoDense, a prospective study in Sweden

Objectives: To assess if mammographic density (MD) changes during neoadjuvant breast cancer treatment and is predictive of a pathological complete response (pCR). Methods: We prospectively included 200 breast cancer patients assigned to neoadjuvant chemotherapy (NACT) in the NeoDense study (2014–2019). Raw data mammograms were used to assess MD with a fully automated volumetric method and radiologists categorized MD using the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. Logistic regression was used to calculate odds ratios (OR) for pCR comparing BI-RADS categories c vs. a, b, and d as well as with a 0.5% change in percent dense volume adjusting for baseline characteristics. Results: The overall median age was 53.1 years, and 48% of study participants were premenopausal pre-NACT. A total of 23% (N = 45) of the patients accomplished pCR following NACT. Patients with very dense breasts (BI-RADS d) were more likely to have a positive axillary lymph node status at diagnosis: 89% of the patients with very dense breasts compared to 72% in the entire cohort. A total of 74% of patients decreased their absolute dense volume during NACT. The likelihood of accomplishing pCR following NACT was independent of volumetric MD at diagnosis and change in volumetric MD during treatment. No trend was observed between decreasing density according to BI-RADS and the likelihood of accomplishing pCR following NACT. Conclusions: The majority of patients decreased their MD during NACT. We found no evidence of MD as a predictive marker of pCR in the neoadjuvant setting

Statin use and breast cancer recurrence in postmenopausal women treated with adjuvant aromatase inhibitors : a Danish population-based cohort study

Purpose: To examine the association between statin use and risk of breast cancer recurrence in a national Danish cohort of postmenopausal breast cancer patients receiving aromatase inhibitors (AI) in the adjuvant setting. Patients and methods: We enrolled all postmenopausal patients diagnosed with stage I–III estrogen receptor positive breast cancer during the years 2007–2017, assigned adjuvant AI treatment, and registered in both the Danish Breast Cancer Group database and the Danish Cancer Registry. We ascertained incident statin exposure (≥ 1 prescription post-diagnosis) from the Danish National Prescription Registry and modeled statins as a time-varying exposure lagged by 6 months. Follow-up began 7 months after diagnosis and continued to the first event of recurrence, death, emigration, 5 years elapsed, or 25th September 2018. We estimated incidence rates of recurrence at 5 years and used Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing statin exposure with non-exposure. Results: We enrolled 14,773 eligible patients. During the 5 years of follow-up, there were 32 recurrences in 3163 person-years of follow-up among statin-exposed patients, and 612 recurrences in 45,655 person-years among unexposed patients (incidence rate per 1000 person-years: 10.12 [95% CI 6.92–14.28] and 13.40 [95% CI 12.36–14.51], respectively). In multivariable models, any statin exposure was associated with a reduced rate of 5-year breast cancer recurrence (adjusted HR 0.72 [95% CI 0.50–1.04]). Considering only lipophilic statins as exposure the results were similar (adjusted HR 0.70 [95% CI 0.48–1.02]). Conclusions: Statin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received adjuvant AI therapy