Practical Experience with the Use of Electronic Headache Diaries and Video Consultations in Migraine Care from a Longitudinal Cohort Study.

Background: Telemedicine offers a promising solution to enhance the delivery and personalization of headache care. Integrating electronic (e-)tools enables the objective monitoring of migraine. Objectives: This study aims to demonstrate the relevance of e-tools for personalized headache care, assess patient and caregiver compliance and satisfaction, and present their use in enhancing care. Methods: Firstly, a systematic review was performed to validate the diagnostic accuracy of e-diaries for diagnosing migraine. Secondly, we collected e-diary data prospectively from diagnosed adult migraine patients at the Leiden Headache Center. Finally, questionnaires were sent to evaluate satisfaction of patients and health care providers with the Leiden e-headache diary and video consultations. Results: In the systematic review, the Leiden Headache Center's e-diary was the only validated tool. Patients (n = 1,009) were followed for a median of 181 days (interquartile range [IQR] 84-240). Compliance was 96.4% (IQR 85.2 - 99.1%), with 10.8% of days missing. Factors positively associated with compliance were older age (p < 0.001), female sex (p < 0.001), higher e-diary grade (p < 0.001), and clinical use (p = 0.04). The e-diary received a median score of 8/10 and was well-liked by patients (n = 535) and providers (n = 23). Video consultations were a good alternative for physical visits according to 76.9% of patients and 84.6% of providers. Conclusion: Validated e-headache diaries and video consultations in telemedicine enhance headache care accessibility, providing convenient care at preferred times and locations.

Lessons learned from Dutch medical disciplinary law regarding aortic aneurysm and dissection care.

OBJECTIVES: The current study is an explanatory analysis of Dutch disciplinary law regarding aortic aneurysm and aortic dissection care. We aim to give insight in the way disciplinary judges rule on quality of care and to extract the lessons to be learned. METHODS: The online open-access governmental database, which includes all disciplinary rulings since 2010, was searched using search terms related to aortic aneurysm and dissection care. First, abstracts were screened for relevance. Thereafter, the full text of all remaining cases was read. Cases related to the diagnosis, treatment, or the postoperative phase of an aortic aneurysm or aortic dissection were included. Characteristics were registered and analyzed for quantitative assessment. Each case was summarized and coded for qualitative analysis. RESULTS: Forty-eight first-instance cases were included, of which 19 (40%) were founded. Reprimands (n=9) and warnings (n=7) were the prevailing measures. Seven out of 8 appeal cases filed by plaintiffs were unfounded. Six out of 9 appeals filed by defendants were adjudged and led to a less severe measure. Most cases concerned the subject of 'wrong treatment/wrong diagnosis' (75%). Whether not recognizing an aneurysm or dissection led to disciplinary culpability depended on case-specific circumstances, and much importance was attached to adequate documentation. In many complaints, an element of inadequate communication was recognized. CONCLUSIONS: Patient-involvement, clear communication, and implementing changes after a mistake could increase patient satisfaction, avert complaints, and prevent time-consuming trials. Maintaining adequate documentation and having knowledge on the analytical framework of the court is beneficial when confronted with a complaint.

Safety considerations in the treatment with anti-CGRP(R) monoclonal antibodies in patients with migraine.

Background: Anti-CGRP-(receptor-)monoclonal antibodies (anti-CGRP(R)-mAbs) represent a novel class of drugs for migraine treatment, but their long-term cerebrovascular and cardiovascular (CV) safety warrants further examination. Methods: In this observational cohort study we assessed the CV safety for erenumab and fremanezumab in a real-world setting during a follow-up period of at least 1 year. Patients with hypertension or CV history were excluded. We conducted ECGs and collected clinical data at treatment initiation and thereafter every 3 months, including liver and kidney function, lipid-, electrolyte-and glucose levels. Results: Among patients receiving erenumab (n = 101) or fremanezumab (n = 92), 3.1% (6/193) developed abnormal ECGs or CV adverse events. Of these, three (1.6%) experienced moderate to severe CV adverse events (cerebellar stroke, spontaneous coronary artery dissection, and pericarditis) and discontinued treatment. The remaining three (1.6%) developed non-threatening ECG abnormalities without physical complaints. No significant changes were observed in liver and kidney function, lipid-, electrolyte-, or glucose levels. Discussion: We observed CV events in 1.6% of patients with 1.5-year follow-up of anti-CGRP(R)-mAbs treatment. We advise awareness regarding CV events in patients with migraine undergoing CGRP-targeted treatment, not as a confirmation of increased risk but as a proactive measure to address potential multifactorial influences.

Early life body size and puberty markers as predictors of breast cancer risk later in life: A neural network analysis.

BACKGROUND: The early life factors of birthweight, child weight, height, body mass index (BMI) and pubertal timing are associated with risks of breast cancer. However, the predictive value of these factors in relation to breast cancer is largely unknown. Therefore, using a machine learning approach, we examined whether birthweight, childhood weights, heights, BMIs, and pubertal timing individually and in combination were predictive of breast cancer. METHODS: We used information on birthweight, childhood height and weight, and pubertal timing assessed by the onset of the growth spurt (OGS) from 164,216 girls born 1930-1996 from the Copenhagen School Health Records Register. Of these, 10,002 women were diagnosed with breast cancer during 1977-2019 according to a nationwide breast cancer database. We developed a feed-forward neural network, which was trained and tested on early life body size measures individually and in various combinations. Evaluation metrics were examined to identify the best performing model. RESULTS: The highest area under the receiver operating curve (AUC) was achieved in a model that included birthweight, childhood heights, weights and age at OGS (AUC = 0.600). A model based on childhood heights and weights had a comparable AUC value (AUC = 0.598), whereas a model including only childhood heights had the lowest AUC value (AUC = 0.572). The sensitivity of the models ranged from 0.698 to 0.760 while the precision ranged from 0.071 to 0.076. CONCLUSION: We found that the best performing network was based on birthweight, childhood weights, heights and age at OGS as the input features. Nonetheless, this performance was only slightly better than the model including childhood heights and weights. Further, although the performance of our networks was relatively low, it was similar to those from previous studies including well-established risk factors. As such, our results suggest that childhood body size may add additional value to breast cancer prediction models.

Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!).

BACKGROUND: Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic. METHODS: Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 µg or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days. RESULTS: The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks - 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD. CONCLUSIONS: The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible. TRIAL REGISTRATION: Clinical trials.gov NCT04007874 . Registered 28 June 2019.

Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine.

BACKGROUND AND PURPOSE: The aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to determine whether depressive symptoms predict treatment response. METHODS: Patients with migraine treated with erenumab and fremanezumab at the Leiden Headache Centre completed daily E-headache diaries. A control group was included. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D) questionnaires at baseline (T0) and after 3 months (T1). First, the effect of treatment on the reduction in HADS-D and CES-D scores was assessed, with reduction in depression scores as the dependent variable and reduction in monthly migraine days (MMD) and treatment with anti-CGRP medication as independent variables. Second, depression as a predictor of treatment response was investigated, using the absolute reduction in MMD as a dependent variable and age, gender, MMD, active depression, impact, stress and locus of control scores as independent variables. RESULTS: In total, n = 108 patients were treated with erenumab, n = 90 with fremanezumab and n = 68 were without active treatment. Treatment with anti-CGRP medication was positively associated with a reduction in the HADS-D (ß = 1.65, p = 0.01) compared to control, independent of MMD reduction. However, the same effect was not found for the CES-D (ß = 2.15, p = 0.21). Active depression predicted poorer response to erenumab (p = 0.02) but not to fremanezumab (p = 0.09). CONCLUSION: Anti-CGRP (ligand or receptor) monoclonals lead to improvement of depressive symptoms in individuals with migraine, independent of migraine reduction. Depression may predict treatment response to erenumab but not to fremanezumab.

The association between sarcopenia and adverse outcomes after complex endovascular aortic repair.

BACKGROUND: Sarcopenia is identified as a predictive factor for adverse outcomes after complex endovascular aortic repair (complex EVAR). Consensus on preferred parameters for sarcopenia is not yet reached. The current study compares three CT-assessed parameters on their association with adverse outcomes after complex EVAR. METHODS: This was a single-center retrospective cohort study. Psoas Muscle Index (PMI), Skeletal Muscle Index (SMI), and lean psoas muscle area (LPMA) were examined by CT-segmentation. PMI, SMI, and LPMA were analyzed as continuous variables. In addition, cut-off values from previous research were used to diagnose patients as sarcopenic or non-sarcopenic. Outcomes were: all-cause mortality, major adverse events (MAE), length of hospital stay, and non-home discharge. A sub-analysis was made for severe sarcopenia; sarcopenia combined with low physical performance (gait speed, Time Up and Go test, Metabolic Equivalent of Task-score). RESULTS: We included 101 patients. A higher PMI (HR=0.590, CI: 0.374-0.930, P=0.023), SMI (HR=0.453, CI: 0.267-0.768, P=0.003), and LPMA (HR=0.559, CI: 0.333-0.944, P=0.029) were associated with a lower risk of mortality. Sarcopenia based on cut-off values for PMI and LPMA was not significantly associated with survival. Sarcopenia based on SMI did present a higher mortality risk (P=0.017). A sub-analysis showed that severely sarcopenic patients were at even higher risk of mortality (P=0.036). None of the parameters were significantly associated with the other outcomes. CONCLUSIONS: SMI had a slightly stronger association with mortality compared to PMI and LPMA. High-risk patients were selected by adding physical performance scores. Future research could focus on complex EVAR-specific PMI and LPMA cut-off values.

Trajectories of body mass index across the lifecourse and associations with post-menopausal breast cancer by estrogen receptor status.

BACKGROUND: Associations between a high body mass index (BMI) at single timepoints during child- and adulthood and risks of post-menopausal breast cancer are well-established, but associations with BMI across the lifecourse remains largely unknown. Therefore, we examined whether lifecourse BMI trajectories were associated with risks of post-menopausal breast cancer overall and by estrogen receptor (ER) status. METHODS: We included 6698 Danish women born 1930-1946. Information on BMI at ages 6-15 years came from the Copenhagen School Health Records Register, and information on BMI at ages 20, 30, 40, 50 and/or 50-64 years came from the Diet, Cancer and Health cohort. Breast cancer cases (n = 577) were identified in the Danish Breast Cancer Cooperative Group database. Six BMI trajectories were identified using latent class trajectory modelling. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models. RESULTS: Compared to women with a trajectory characterized by an average BMI gain across life, women with the two trajectories with steep increases in BMI during childhood and adolescence that thereafter largely stabilized, had lower risks of post-menopausal breast cancer and ER-positive tumors. The adjusted HRs for ER-positive tumors were 0.67 (95% CI: 0.47-0.95) and 0.68 (95% CI: 0.46-1.01), respectively. In contrast, women with a trajectory with a low gain in BMI during childhood and adolescence followed by a subsequent steep increase during adulthood, had higher risks of post-menopausal breast cancer and ER-positive tumors when compared to women with an average BMI gain. The adjusted HR for ER-positive tumors was 1.28 (95% CI: 0.98-1.67). CONCLUSIONS: Our findings suggest that the timing of excess gain in BMI across the lifecourse impacts subsequent post-menopausal breast cancer risks. Thus, the BMI development across life is likely useful in the identification of women at increased risks of post-menopausal breast cancer.

Effect of COVID vaccination on monthly migraine days: a longitudinal cohort study.

BACKGROUND: This longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination. METHODS: We identified 547 clinically diagnosed migraine patients from the Leiden Headache Center who kept a headache E-diary during the COVID-19 pandemic (February 2020 to August 2022). We sent a questionnaire to register their COVID-19 infection and/or vaccination dates. After applying inclusion criteria, n = 59 participants could be included in the infection analysis and n = 147 could be included in the vaccination analysis. Primary outcome was the change in monthly migraine days (MMD) between 1 month prior and 1 month post COVID-19 infection or vaccination. Secondary outcome variables were change in monthly headache days (MHD) and monthly acute medication days (MAMD). RESULTS: Vaccination against COVID-19 was associated with an increase in MMD (1.06; 95% confidence interval [CI] = 0.57-1.55; p < 0.001), MHD (1.52; 95% CI = 0.91-2.14; p < 0.001) and MAMD (0.72; 95% CI = 0.33-1.12; p < 0.001) in the first month post-vaccination. COVID-19 infection solely increased the number of MAMD (1.11; 95% CI = 0.10-1.62; p < 0.027), but no statistically significant differences in MMD or MHD were observed. CONCLUSIONS: Our findings imply that vaccination against COVID-19 is associated with an increase in migraine, indicating a possible role of inflammatory mediators in migraine pathophysiology.

Defining migraine days, based on longitudinal E-diary data.

BACKGROUND: There is a need for standardization of the definition of a migraine day for clinical and research purposes. METHODS: We prospectively compared different definitions of a migraine day with E-diary data of n = 1494 patients with migraine. We used a baseline definition based on migraine characteristics with a duration of ≥4 hours OR triptan intake (independently from its effect) OR (visual) aura lasting 5-60 minutes. RESULTS: Of all migraine days defined by triptan intake only, 66.2% had a duration <4 hours. Adjusting the headache duration criterion to ≥30 minutes led to a decrease in days defined by triptan intake only and resulted in a 5.4% increase in total migraine days (equals 0.45 migraine day increase in monthly migraine days). These additional migraine days had a median duration of 2.5 hours. CONCLUSION: We propose to define a migraine day as follows: 1) (a) headache duration ≥30 minutes; (b) matching ≥2 of four characteristics: unilateral, pulsating, moderate to severe pain, aggravation by or causing avoidance of routine physical activity; and (c) during headache ≥1 of the following: nausea and/or vomiting, photophobia and phonophobia or 2) (visual) aura duration 5-60 minutes or 3) a day with headache for which acute migraine-specific medication is used irrespective of its effect.

Both perimenstrual and nonperimenstrual migraine days respond to anti-calcitonin gene-related peptide (receptor) antibodies.

BACKGROUND AND PURPOSE: Anti-calcitonin gene-related peptide (CGRP) (receptor) antibodies effectively reduce overall migraine attack frequency, but whether there are differences in effect between perimenstrual and nonperimenstrual migraine days has not been investigated. METHODS: We performed a single-arm study among women with migraine. Participants were followed with electronic E-diaries during one (pretreatment) baseline month and 6 months of treatment with either erenumab or fremanezumab. Differences in treatment effect on perimenstrual and nonperimenstrual migraine days were assessed using a mixed effects logistic regression model, with migraine day as dependent variable; treatment, menstrual window, and an interaction term (treatment × menstrual window) as fixed effects; and patient as a random effect. RESULTS: There was no interaction between the menstrual window and treatment effect, indicating that the reduction in migraine days under treatment was similar during the menstrual window and the remainder of the menstrual cycle (odds ratio for treatment = 0.44, 95% confidence interval = 0.38-0.51). CONCLUSIONS: Our findings support prophylactic use of anti-CGRP (receptor) antibodies for women with menstrual migraine, as this leads to consistent reductions in number of migraine days during the entire menstrual cycle.

Sex differences in migraine attack characteristics: A longitudinal E-diary study.

OBJECTIVE: In this prospective cohort study, characteristics of perimenstrual and non-perimenstrual migraine attacks in women were compared with migraine attacks in men. BACKGROUND: Women report longer migraine attacks and more accompanying symptoms than men in cross-sectional questionnaire studies, but this has not been confirmed in longitudinal studies. Supposed differences could result from different characteristics specific to perimenstrual migraine attacks, or of attacks in women in general. METHODS: This cohort study was performed among patients with migraine who were treated at the Leiden Headache Clinic. We assessed differences in migraine attack characteristics between men and women who were prospectively followed by a previously validated electronic headache diary. The primary outcome was "attack" duration. Differences between perimenstrual (Days -2 to +3 of the menstrual cycle) and non-perimenstrual attacks in women versus attacks in men were corrected for age, chronic migraine, and medication overuse headache. RESULTS: A total of 1347 women and 284 men were included, reflecting the preponderance of women in migraine prevalence. Crude median (first and third quartile [Q1-Q3]) attack duration in men was 32.1 [17.7-53.6] h, compared to 36.7 [21.9-62.4] h for non-perimenstrual migraine attacks and 44.4 [17.9-79.0] h for perimenstrual migraine attacks in women. After correction for confounding, perimenstrual migraine attacks were 1.62 (95% confidence interval [CI] 1.47-1.79; p < 0.001) and non-perimenstrual 1.15 (95% CI 1.05-1.25; p = 0.003) times longer compared to migraine attacks in men. The mean relapse percentage in men was 9.2%, compared to 12.6% for non-perimenstrual migraine attacks, and 15.7% for perimenstrual migraine attacks. Relapse risk was greater for perimenstrual (odds ratio [OR] 2.39, 95% CI 1.93-2.95; p < 0.001), but not for non-perimenstrual (OR 1.18, 95% CI 0.97-1.45; p = 0.060) attacks. Migraine attacks in women were more often accompanied by photophobia, phonophobia, and nausea, but less often aura. CONCLUSION: Compared to attacks in men, both perimenstrual and non-perimenstrual migraine attacks are of longer duration and are more often accompanied by associated symptoms. A sex-specific approach to migraine treatment and research is needed.

Learning Curve Analysis of Complex Endovascular Aortic Repair.

BACKGROUND: When introducing new techniques, attention must be paid to learning curve. Besides quantitative outcomes, qualitative factors of influence should be taken into consideration. This retrospective cohort study describes the quantitative learning curve of complex endovascular aortic repair (EVAR) in a nonhigh-volume academic center and provides qualitative factors that were perceived as contributors to this learning curve. With these factors, we aim to aid in future implementation of new techniques. METHODS: All patients undergoing complex EVAR in the Leiden University Medical Center (LUMC) between July 2013 and April 2021 were included (n = 90). Quantitative outcomes were as follows: operating time, blood loss, volume of contrast, hospital stay, major adverse events (MAE), 30-day mortality, and complexity. Patients were divided into 3 temporal groups (n = 30) for dichotomous outcomes. Regression plots were used for continuous outcomes. In 2017, the treatment team was interviewed by an external researcher. These interviews were reanalyzed for factors that contributed to successful implementation. RESULTS: Length of hospital stay (P = 0.008) and operating time (P = 0.010) decreased significantly over time. Fewer cardiac complications occurred in the third group (3: 0% vs. 2: 17% vs. 1: 17%, P = 0.042). There was a trend of increasing complexity (P = 0.076) and number of fenestrations (P = 0.060). No significant changes occurred in MAE and 30-day mortality. Qualitative factors that, according to the interviewees, positively influenced the learning curve were as follows: communication, mutual trust, a shared sense of responsibility and collective goals, clear authoritative structures, mutual learning, and team capabilities. CONCLUSIONS: In addition to factors previously identified in the literature, new learning curve factors were found (mutual learning and shared goals in the operating room (OR)) that should be taken into account when implementing new techniques.

Birth weight, childhood body mass index, and risk of diverticular disease in adulthood.

OBJECTIVE: Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD. METHODS: Cohort study of 346,586 persons born during 1930-1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z-scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18-49 and from age 50. RESULTS: During follow-up, 5459 (3.2%) women and 4429 (2.5%) men had DD. For low and high BMI in childhood, we observed a higher risk of DD before age 50. Among women with z-scores <0 at age 13, the hazard ratio (HR) was 1.16 [95% confidence interval (CI): 0.98-1.39] per one-point lower z-score. For z-scores ≥0 at age 13, the HR was 1.30 (95% CI: 1.11-1.51) per one-point higher z-score. Among men with z-scores <0 at age 13, the HR was 1.02 (95% CI: 0.85-1.22). For z-scores ≥0 at age 13, the HR was 1.54 (95% CI: 1.34-1.78). Z-scores ≥0 were not associated with DD after age 50. Among women only, birthweight was inversely associated with DD before age 50 [HR = 0.90 (95% CI: 0.83-0.99) per 500 g higher birthweight]. CONCLUSION: BMI z-scores below and above zero in childhood were associated with higher risk of DD before age 50. In addition, we observed lower risk of DD among women, the higher their birthweight.

Combining text mining with clinical decision support in clinical practice: a scoping review.

OBJECTIVE: Combining text mining (TM) and clinical decision support (CDS) could improve diagnostic and therapeutic processes in clinical practice. This review summarizes current knowledge of the TM-CDS combination in clinical practice, including their intended purpose, implementation in clinical practice, and barriers to such implementation. MATERIALS AND METHODS: A search was conducted in PubMed, EMBASE, and Cochrane Library databases to identify full-text English language studies published before January 2022 with TM-CDS combination in clinical practice. RESULTS: Of 714 identified and screened unique publications, 39 were included. The majority of the included studies are related to diagnosis (n = 26) or prognosis (n = 11) and used a method that was developed for a specific clinical domain, document type, or application. Most of the studies selected text containing parts of the electronic health record (EHR), such as reports (41%, n = 16) and free-text narratives (36%, n = 14), and 23 studies utilized a tool that had software "developed for the study". In 15 studies, the software source was openly available. In 79% of studies, the tool was not implemented in clinical practice. Barriers to implement these tools included the complexity of natural language, EHR incompleteness, validation and performance of the tool, lack of input from an expert team, and the adoption rate among professionals. DISCUSSION/CONCLUSIONS: The available evidence indicates that the TM-CDS combination may improve diagnostic and therapeutic processes, contributing to increased patient safety. However, further research is needed to identify barriers to implementation and the impact of such tools in clinical practice.

Childhood body mass index trajectories, adult-onset type 2 diabetes, and obesity-related cancers.

BACKGROUND: Elevated childhood body mass index (BMI), commonly examined as a "once-only" value, increases the risk of cancer and type 2 diabetes (T2D) in adulthood. Continuous exposure to adiposity during childhood may further increase cancer risk. We examined whether longitudinal childhood BMI trajectories were associated with adult obesity-related cancer and the role of adult-onset T2D in these associations. METHODS: Five sex-specific latent class BMI trajectories were generated for 301 927 children (149 325 girls) aged 6-15 years from the Copenhagen School Health Records Register. Information on obesity-related cancers and T2D was obtained from national health registers. Incidence rate ratios (IRR), cumulative incidences, and confidence intervals (CI) were estimated using Poisson regressions. RESULTS: Compared with the average childhood BMI trajectory (containing approximately 40% of individuals), the rate of obesity-related cancer (excluding breast cancer) increased with higher childhood BMI trajectories among women. The highest rates occurred in the overweight (IRR = 1.27, 95% CI = 1.17 to 1.38) and obesity (IRR = 1.79, 95% CI = 1.53 to 2.08) BMI trajectories. Similar patterns were observed among men. In contrast, women with the obesity childhood BMI trajectory had the lowest rate of pre- and postmenopausal breast cancer (IRR = 0.59, 95% CI = 0.43 to 0.80, and IRR = 0.41, 95% CI = 0.30 to 0.57, respectively). For all trajectories, the cumulative risk of obesity-related cancer increased with adult-onset T2D. CONCLUSION: Consistent childhood overweight or obesity may increase the rates of adult obesity-related cancer and decrease the rates of breast cancer. Adult-onset T2D conferred additional risk for obesity-related cancer, but the effect did not differ across childhood BMI trajectories.

Birthweight, childhood body size, and timing of puberty and risks of breast cancer by menopausal status and tumor receptor subtypes.

BACKGROUND: Associations of birthweight, childhood body size and pubertal timing with breast cancer risks by menopausal status and tumor receptor subtypes are inconclusive. Thus, we investigated these associations in a population-based cohort of Danish women. METHODS: We studied 162,419 women born between 1930 and 1996 from the Copenhagen School Health Records Register. The register includes information on birthweight, measured childhood weights and heights at the age of 7-13 years, and computed ages at the onset of the growth spurt (OGS) and at peak height velocity (PHV). The Danish Breast Cancer Cooperative Group database provided information on breast cancer (n = 7510), including estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and menopausal status. Hormone replacement therapy use came from the Danish National Prescription Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression. RESULTS: We found that birthweight was not associated with any breast cancer subtypes. While childhood BMI was not statistically significantly associated with ER+ tumors nor consistently with ER- tumors among pre-menopausal women, consistent inverse associations were found among postmenopausal women. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 0.90 (95% CI 0.87-0.93) and 0.84 (95% CI 0.79-0.91) per BMI z-score, respectively. Similarly, childhood BMI was inversely associated with pre- and postmenopausal HER2- tumors, but not with HER2+ tumors. Childhood height was positively associated with both pre- and postmenopausal ER+ tumors, but not with ER- tumors. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 1.09 (95% CI 1.06-1.12) and 1.02 (95% CI 0.96-1.09) per height z-score, respectively. In general, childhood height was positively associated with HER2+ and HER2- tumors among pre- and postmenopausal women. Ages at OGS and PHV were not associated with any breast cancer subtypes. CONCLUSIONS: We showed that a high BMI and short stature in childhood are associated with reduced risks of certain breast cancer subtypes. Thus, childhood body composition may play a role in the development of breast cancer.

Blood Pressure in Patients With Migraine Treated With Monoclonal Anti-CGRP (Receptor) Antibodies: A Prospective Follow-up Study.

BACKGROUND AND OBJECTIVES: Anti-calcitonin gene-related peptide (CGRP) (receptor) antibodies are approved as preventive treatment for migraine. Recent concerns have been raised after a retrospective analysis of postmarketing case reports of elevated blood pressure (BP) associated with erenumab. In this prospective follow-up study, we aimed to assess the safety regarding BP in a real-world setting. METHODS: All people with migraine who were treated with erenumab and fremanezumab at the Leiden Headache Center between January 2019 and January 2021 were included. BP measurements were collected from baseline (T0) until 12 months of follow-up, with a 3-month interval (T1-T4). Mixed linear models were fitted with time as a fixed effect and the patient as a random effect. RESULTS: Both systolic and diastolic BP were increased at all time points T1-T4 compared with T0 (p < 0.001). The maximum estimated increase in the mean systolic BP was 5.2 mm Hg (95% CI 3.1-7.5). The maximum estimated increase in the mean diastolic BP was 3.5 mm Hg (95% CI 2.0-4.9). In the erenumab group (n = 109), both systolic and diastolic BP were increased at all time points compared with T0 (all p < 0.001). For fremanezumab (n = 87), systolic but not diastolic BP was increased compared with T0 at T1 (p = 0.006) and T2 (p = 0.004). Four patients (3.7%) with normal BP at T0 required antihypertensive treatment after erenumab was started. DISCUSSION: The mean systolic and diastolic BP increased after anti-CGRP (receptor) antibodies were started. The majority of patients remained within the normal BP limits, but some patients required antihypertensive treatment. Physicians should be aware that people with migraine may be at risk of developing hypertension when treated with anti-CGRP (receptor) antibodies, and this should be added to (inter)national treatment guidelines. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anti-CGRP (receptor) antibodies increase BP when used to treat patients with migraine.

Childhood body mass index trajectories and associations with adult-onset chronic kidney disease in Denmark: A population-based cohort study.

BACKGROUND: Although excess adult adiposity is a strong risk factor for chronic kidney disease (CKD), evidence for associations with early life body size is limited. We investigated whether childhood body mass index (BMI) trajectories are associated with adult-onset CKD and end-stage kidney disease (ESKD) using a population-based cohort. Further, we examined the role of adult-onset type 2 diabetes (T2D) in these associations. METHODS AND FINDINGS: We included 151,506 boys and 148,590 girls from the Copenhagen School Health Records Register, born 1930 to 1987 with information on measured weights and heights at ages 6 to 15 years. Five sex-specific childhood BMI trajectories were analyzed. Information on the main outcomes CKD and ESKD, as well as T2D, came from national health registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using Poisson regression adjusted for year of birth. During a median of 30.8 person-years of follow-up, 5,968 men and 3,903 women developed CKD and 977 men and 543 women developed ESKD. For both sexes, the rates of CKD and ESKD increased significantly with higher child BMI trajectories in comparison with the average BMI trajectory (40% to 43% of individuals) and the below-average BMI trajectory (21% to 23% of individuals) had the lowest rates. When including T2D, most associations were significant and men (IRR = 1.39, 95% CI: 1.13 to 1.72) and women (IRR = 1.54, 95% CI: 1.28 to 1.86) with the obese childhood BMI trajectory (2% of individuals) had significantly higher CKD rates than the average BMI trajectory, whereas for ESKD, the associations were positive, but nonsignificant, for men (IRR = 1.38, 95% CI: 0.83 to 2.31) but significant for women (IRR = 1.97, 95% CI: 1.25 to 3.11) with the obese BMI trajectory. A main study limitation is the use of only hospital-based CKD diagnoses. CONCLUSIONS: Individuals with childhood BMI trajectories above average had higher rates of CKD and ESKD than those with an average childhood BMI trajectory. When including T2D, most associations were significant, particularly with CKD, emphasizing the potential information that the early appearance of above-average BMI growth patterns provide in relation to adult-onset CKD beyond the information provided by T2D development.

Body mass index trajectories in childhood and incidence rates of type 2 diabetes and coronary heart disease in adulthood: A cohort study.

AIMS: We examined associations between five body mass index (BMI) trajectories from ages 6-15 years and register-based adult-onset type 2 diabetes mellitus (T2D) and coronary heart disease (CHD) with and without adjustment for adult BMI. METHODS: Child and adult BMI came from two Danish cohorts and 13,205 and 13,438 individuals were included in T2D and CHD analyses, respectively. Trajectories were estimated by latent class modelling. Incidence rate ratios (IRRs) were estimated with Poisson regression. RESULTS: In models without adult BMI, compared to the lowest trajectory, among men the T2D IRRs were 0.92 (95 %CI:0.77-1.09) for the second lowest trajectory and 1.51 (95 %CI:0.71-3.20) for the highest trajectory. The corresponding IRRs in women were 0.92 (95 %CI:0.74-1.16) and 3.58 (95 %CI:2.30-5.57). In models including adult BMI, compared to the lowest trajectory, T2D IRRs in men were 0.57 (95 %CI:0.47-0.68) for the second lowest trajectory and 0.26 (95 %CI:0.12-0.56) for the highest trajectory. The corresponding IRRs in women were 0.60 (95 %CI:0.48-0.75) and 0.59 (95 %CI:0.36-0.96). The associations were similar in direction, but not statistically significant, for CHD. CONCLUSIONS: Incidence rates of adult-onset T2D were greater for a high child BMI trajectory than a low child BMI trajectory, but not in models that included adult BMI.