Effectiveness of galcanezumab on sleep quality, migraine outcome, and multidimensional patient-reported outcome measures: a real-world experience in Turkish patients with episodic and chronic migraine.

Introduction: This real-world study aimed to investigate the impact of galcanezumab on sleep quality, migraine outcome and multidimensional patient-reported outcomes measures (PROMs) in patients with episodic migraine (EM) and chronic migraine (CM). Methods: Fifty-four patients with episodic migraine (n = 24) or chronic migraine (n = 30) received a 3-month series of galcanezumab injections and were evaluated for sleep quality, measured using the Pittsburgh Sleep Quality Index (PSQI), as well as migraine outcomes such as monthly headache days (MHDs), monthly migraine days (MMDs), and headache severity. Patient-reported outcome measures (PROMs) such as the Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6), SF-36 Health-related Quality of Life (HRQoL), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were additionally included in the assessment. Results: The percentage of patients with poor sleep quality (total PSQI scores ≥ 5) was 72.7% at baseline, decreasing to 57.5% and 56.2% at the 1st and 2nd months, respectively. By the 3rd month of galcanezumab injections, significant improvement was observed in the sleep disturbances domain in the overall study population (p = 0.016), and in subgroups of patients with low anxiety levels (p = 0.016) and none/minimal depression (p = 0.035) at baseline. Patients with sleep disorder at baseline exhibited marked improvements in total PSQI scores (p = 0.027) and in the subjective sleep quality (p = 0.034) and daytime dysfunction (p = 0.013) domains, by the 3rd month. Over the 1st, 2nd, and 3rd months, there were significant improvements in MHDs (p < 0.001), MMDs (p < 0.001), HIT-6 scores (p < 0.001 for each), BAI scores (p < 0.001 for each), BDI scores (p ranged from 0.048 to <0.001), and HRQoL scores (p ranged from 0.012 to <0.001). Conclusion: Galcanezumab demonstrates notable benefits in improving sleep quality, along with a comorbidity-based and domain-specific effect on sleep parameters, which involved sleep disturbances domain in patients without depression or anxiety at baseline but the total PSQI scores, subjective sleep quality and daytime dysfunction in those with sleep disorder at baseline. The treatment also facilitates rapid-onset enhancements in migraine outcomes as well as various PROMs.

The Assessment of Clinical Characteristics, Treatment Patterns, and Burden of Illness in Patients With Episodic and Chronic Migraine: A Cross-Sectional Study.

INTRODUCTION: Migraine is a prevalent and disabling primary headache disorder worldwide, causing significant years lost due to disability (YLD) and impacting various aspects of everyday life. Despite its high prevalence and substantial burden, there is a lack of comprehensive data on clinical patterns and management trends, in places like Tamil Nadu, India. This study aims and also fill gaps by investigating and analyzing the clinical characteristics, treatment patterns, and illness burden among patients with episodic migraine (EM) and chronic migraine (CM) in the state of Tamil Nadu. STUDY: This cross-sectional retrospective study was conducted at the Department of Neurology, Madras Medical College, Chennai, over a three-month period starting from January 2024 to March 2024. The study included migraine patients aged 18 years and above who met the International Classification of Headache Disorders (ICHD)-3 criteria and took treatment at the department. Data were collected using patient interviews, medical records, and counseling sessions and using a pre-designed questionnaire. Patient demographics, clinical characteristics, symptom prevalence, prescription patterns, and illness burden were analyzed accordingly. The Migraine Disability Assessment (MIDAS) questionnaire was used to measure the burden of illness. RESULTS: The analysis involved 400 migraine patients, 92.5% of them having EM and 7.5% of them having CM. The mean age of patients was 37.5 years, with a predominance of females (73.5%). Patients with CM had having significantly higher average number of headache days per month when compared to those with EM. Tension-type headache (TTH) and medication-overuse headache (MOH) were more prevalent in those CM patients. Trigger factors include lack of sleep, bright light exposure, and stress. Comorbidities such as diabetes mellitus, obesity, and depression were significantly higher in CM patients. Acute treatment included NSAIDs and Triptans, while preventive therapy was more commonly used in CM patients. The mean MIDAS score was significantly higher in CM patients, which indicates greater disability. CONCLUSION: The study provides valuable insights into the clinical characteristics, treatment patterns, and burden of illness among migraine patients in Tamil Nadu, India. Significant differences were observed between EM and CM patients, which highlights the need for comprehensive management strategies. Preventive therapy, lifestyle modifications, and comprehensive assessment of disability are all important in addressing the variable needs of migraine patients and also reducing the burden of illness. Further research is necessary to explore additional factors influencing migraine outcomes in this population.

RAD52-dependent mitotic DNA synthesis is required for genome stability in Cyclin E1-overexpressing cells.

Overexpression of Cyclin E1 perturbs DNA replication, resulting in DNA lesions and genomic instability. Consequently, Cyclin E1-overexpressing cancer cells increasingly rely on DNA repair, including RAD52-mediated break-induced replication during interphase. We show that not all DNA lesions induced by Cyclin E1 overexpression are resolved during interphase. While DNA lesions upon Cyclin E1 overexpression are induced in S phase, a significant fraction of these lesions is transmitted into mitosis. Cyclin E1 overexpression triggers mitotic DNA synthesis (MiDAS) in a RAD52-dependent fashion. Chemical or genetic inactivation of MiDAS enhances mitotic aberrations and persistent DNA damage. Mitosis-specific degradation of RAD52 prevents Cyclin E1-induced MiDAS and reduces the viability of Cyclin E1-overexpressing cells, underscoring the relevance of RAD52 during mitosis to maintain genomic integrity. Finally, analysis of breast cancer samples reveals a positive correlation between Cyclin E1 amplification and RAD52 expression. These findings demonstrate the importance of suppressing mitotic defects in Cyclin E1-overexpressing cells through RAD52.

Effects of Gluten on Gut Microbiota in Patients with Gastrointestinal Disorders, Migraine, and Dermatitis.

As gluten may trigger gastrointestinal disorders (GIDs), its presence or absence in the diet can change the diversity and proportion of gut microbiota. The effects of gluten after six weeks of a double-blind, placebo-controlled intervention with a gluten-free diet (GFD) were studied in participants with GIDs suffering from migraines and atopic dermatitis (n = 46). Clinical biomarkers, digestive symptoms, stool, the Migraine Disability Assessment questionnaire, and zonulin levels were analyzed. Next-generation sequencing was used to amplify the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) regions of fungi. The GFD increased Chao1 fungal diversity after the intervention, while the fungal composition showed no changes. Bacterial diversity and composition remained stable, but a positive association between bacterial and fungal Chao1 diversity and a negative association between Dothideomycetes and Akkermansia were observed. GIDs decreased in both groups and migraines improved in the placebo group. Our findings may aid the development of GID treatment strategies.

Magilock: a reliable control triggering method in multi-channel eye-control systems.

Eye-tracking technology brings a different human-computer interaction experience to users because of its intuitive, natural, and hands-free operation characteristics. Avoiding the Midas touch problem and improving the accuracy of interaction are among the main goals of the research and development of eye-control systems. This study reviews the methods and limitations of research on avoiding the Midas touch problem. For typical control clicking operations with low fault tolerance, such as mode switching and state selection in an eye-control system, this study proposes Magilock, a more reliable control triggering method with a high success rate in multi-channel eye-control systems. Magilock adds a control pre-locked mechanism between the two interactive steps of eye-control channel positioning control and other interactive channel triggering controls in the multi-channel eye-control system. This effectively avoids incorrect control triggering caused by multi-channel coordination disorder and gaze-point drift. This study also conducted ergonomic experiments to explore the lock and unlock times of the control pre-locked mechanism in Magilock. Taking into account the experimental data and subjective evaluation of the participants, we recommend setting the lock time and the unlock time of Magilock to 200 ms.

The cell cycle revisited: DNA replication past S phase preserves genome integrity.

Accurate and complete DNA duplication is critical for maintaining genome integrity. Multiple mechanisms regulate when and where DNA replication takes place, to ensure that the entire genome is duplicated once and only once per cell cycle. Although the bulk of the genome is copied during the S phase of the cell cycle, increasing evidence suggests that parts of the genome are replicated in G2 or mitosis, in a last attempt to secure that daughter cells inherit an accurate copy of parental DNA. Remaining unreplicated gaps may be passed down to progeny and replicated in the next G1 or S phase. These findings challenge the long-established view that genome duplication occurs strictly during the S phase, bridging DNA replication to DNA repair and providing novel therapeutic strategies for cancer treatment.

Premonitory symptoms in migraine: A REFORM Study.

BACKGROUND: Estimates of proportions of people with migraine who report premonitory symptoms vary greatly among previous studies. Our aims were to establish the proportion of patients reporting premonitory symptoms and its dependency on the enquiry method. Additionally, we investigated the impact of premonitory symptoms on disease burden using Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS) and World Health Organization Disability Assessment 2.0 (WHODAS 2.0), whilst investigating how various clinical factors influenced the likelihood of reporting premonitory symptoms. METHODS: In a cross-sectional study, premonitory symptoms were assessed among 632 patients with migraine. Unprompted enquiry was used first, followed by a list of 17 items (prompted). Additionally, we obtained clinical characteristics through a semi-structured interview. RESULTS: Prompted enquiry resulted in a greater proportion reporting premonitory symptoms than unprompted (69.9% vs. 43.0%; p < 0.001) and with higher symptom counts (medians 2, interquartile range = 0-6 vs. 1, interquartile range = 0-1; p < 0.001). The number of symptoms correlated weakly with HIT-6 (ρ = 0.14; p < 0.001) and WHODAS scores (ρ = 0.09; p = 0.041). Reporting postdromal symptoms or triggers increased the probability of reporting premonitory symptoms, whereas monthly migraine days decreased it. CONCLUSIONS: The use of a standardized and optimized method for assessing premonitory symptoms is necessary to estimate their prevalence and to understand whether and how they contribute to disease burden.

Nascent DNA sequencing and its diverse applications in genome integrity research.

Multiple DNA repair pathways and biological responses to DNA damage have evolved to protect cells from various types of lesions to which they are subjected. Although DNA repair systems are mechanistically distinct, all process the damaged region and then insert new bases to fill the gap. In 1969, Robert Painter developed an assay called "unscheduled" DNA synthesis (UDS), which measures DNA repair synthesis as the uptake of radiolabeled DNA precursors distinct from replicative synthesis. Contemporary detection of nascent DNA during repair by next-generation sequencing grants genome-wide information about the nature of lesions that threaten genome integrity. Recently, we developed the SAR-seq (synthesis associated with repair sequencing) method, which provides a high-resolution view of UDS. SAR-seq has been utilized to map programmed DNA repair sites in non-dividing neurons, replication initiation zones, monitor 53BP1 function in countering end-resection, and to identify regions of the genome that fail to complete replication during S phase but utilize repair synthesis during mitosis (MiDAS). As an example of SAR-seq, we present data showing that sites replicated during mitosis correspond to common fragile sites, which have been linked to tumor progression, cellular senescence, and aging.

Monitoring of optic sheath diameter during acute migraine attack: an objective criteria for the severity of disease.

BACKGROUND: The etiology of migraine can be complex and multifactorial but not clear, also, intracranial pressure has been already associated with migraine attacks. This study aimed to monitor intracranial pressure during migraine attack to understand the possible relations with disease and severity. METHODS: A prospective randomized study was designed. Patients with a definitive diagnosis of migraine underwent ultrasonography for optic nerve sheath diameter (ONSD) measurement before treatment and were re-measured after the attack was resolved. The severity of the migraine was assessed with Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment (MIDAS) questionnaire before the treatment and after the symptoms regressed. ONSD values and scores from the questionnaires were compared before and after the migraine attack. RESULTS: The study included 11 (52.4%) women and 10 (47.6%) men, and 42 eyes were evaluated. ONSD was detected as 4.23 ± 0.26 mm in the right eye and 4.10 ± 0.32 mm in the left eye during the migraine attack and decreased to 3.65 ± 0.41 mm in the right eye and 3.50 ± 0.33 mm in the left eye after the attack was treated (p < 0.001, both). A similar statistical improvement was found in HIT-6 and MIDAS scores with ONSD after treatment (p < 0.001). A significant positive correlation was found between the ONSD value in both eyes and HIT-6/MIDAS scores during the migraine attack, and also, after the migraine attack. CONCLUSION: A subjective increase of ONSD values during the migraine attack decreased after the disease resolved, also changes in ONSD values were significantly correlated with the severity of symptoms.

Effect of repetition of vertical and horizontal routes on navigation performance in Australian bull ants.

Solitarily foraging ant species differ in their reliance on their two primary navigational systems- path integration and visual learning. Despite many species of Australian bull ants spending most of their foraging time on their foraging tree, little is known about the use of these systems while climbing. "Rewinding" displacements are commonly used to understand navigational system usage, and work by introducing a mismatch between these navigational systems, by displacing foragers after they have run-down their path integration vector. We used rewinding to test the role of path integration on the arboreal and terrestrial navigation of M. midas. We rewound foragers along either the vertical portion, the ground surface portion, or across both portions of their homing trip. Since rewinding involves repeatedly capturing and releasing foragers, we included a nondisplacement, capture-and-release control, in which the path integration vector is unchanged. We found that rewound foragers do not seem to accumulate path integration vector, although a limited effect of vertical rewinding was found, suggesting a potential higher sensitivity while descending the foraging tree. However, the decrease in navigational efficiency due to capture was larger than the vertical rewinding effect, which along with the negative impact of the vertical surface, and an interaction between capture and rewinding, may suggest aversion rather than path integration caused the vertical rewinding response. Together these results add to the evidence that M. midas makes minimal use of path integration while foraging, and the growing evidence that they are capable of quickly learning from aversive stimulus.

FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination.

Ubiquitination of proliferating cell nuclear antigen (PCNA) at lysine 164 (K164) activates DNA damage tolerance pathways. Currently, we lack a comprehensive understanding of how PCNA K164 ubiquitination promotes genome stability. To evaluate this, we generated stable cell lines expressing PCNAK164R from the endogenous PCNA locus. Our data reveal that the inability to ubiquitinate K164 causes perturbations in global DNA replication. Persistent replication stress generates under-replicated regions and is exacerbated by the DNA polymerase inhibitor aphidicolin. We show that these phenotypes are due, in part, to impaired Fanconi anemia group D2 protein (FANCD2)-dependent mitotic DNA synthesis (MiDAS) in PCNAK164R cells. FANCD2 mono-ubiquitination is significantly reduced in PCNAK164R mutants, leading to reduced chromatin association and foci formation, both prerequisites for FANCD2-dependent MiDAS. Furthermore, K164 ubiquitination coordinates direct PCNA/FANCD2 colocalization in mitotic nuclei. Here, we show that PCNA K164 ubiquitination maintains human genome stability by promoting FANCD2-dependent MiDAS to prevent the accumulation of under-replicated DNA.

Evaluating the effectiveness of the Ministry of Health restriction policy on seasonal antibiotic consumption trends in Saudi Arabia, 2016-2020.

Background: Understanding antibiotic consumption patterns over time is essential to optimize prescribing practices and minimizing antimicrobial resistance. This study aimed to determine whether the antibiotics restriction policy launched by the Saudi Ministry of Health in April 2018 has impacted antibiotic use by assessing changes and seasonal variations following policy enforcement. Methods: Quarterly sales data of J01 antibacterial for systemic use in standard units were obtained from the IQVIA-MIDAS database, spanning from the first quarter of 2016 to the last quarter of 2020. Antibiotics consumption was measured in defined daily doses per 1,000 inhabitant per day- in a quarter (DDDdq). A comparative analysis of antibiotic consumption pre- and post-policy periods introduction was conducted by computing the average consumption values for each period. Statistical comparison of the mean differences between the two periods were then made using independent samples t-test, Mann-Whitney U Test where needed. Time series analysis was employed to estimate the projected antibiotic consumption in the post-policy period if the restriction policy had not been implemented, which was then compared to actual consumption values to evaluate the effectiveness of the restriction policy. Results: During the pre-policy, there were seasonal trends of the total and oral antibiotic consumption through quarters, with higher consumption observed in the first and fourth quarters. In contrast, parenteral antibiotic consumption did not appear to follow a clear seasonal pattern. Following the restriction policy, there was a significant reduction in total and oral antibiotic use, with mean reductions of -96.9 DDDdq (p-value = 0.002) and -98 DDDdq (p-value = 0.002), respectively. Conversely, a significant increase in parenteral antibiotic consumption was observed with a mean increase of +1.4 DDDdq (p-value < 0.0001). The comparison between the forecasted and actual models showed that the actual antibiotics consumption for total, oral, and parenteral were lower than the corresponding forecasted values by 30%, 31%, and 34%, respectively. Conclusion: Overall, our analysis of antibiotics consumption from 2016 to 2020 displays great success for the policy implemented by the Saudi Ministry of Health in significantly reducing the total and oral use of antibiotics. However, future studies are needed to explore the increased consumption of the parenteral antibiotics as well as the persistent high consumption patterns during the fall and winter months even after the implementation of the restriction policy.

Functional outcomes between headache surgery and targeted botox injections: A prospective multicenter pilot study.

Introduction: Chronic migraine headaches (MH) are a principal cause of disability worldwide. This study evaluated and compared functional outcomes after peripheral trigger point deactivation surgery or botulinum neurotoxin A (BTA) treatment in patients with MH. Methods: A long-term, multicenter, and prospective study was performed. Patients with chronic migraine were recruited at the Ohio State University and Massachusetts General Hospital and included in each treatment group according to their preference (BTA or surgery). Assessment tools including the Migraine Headache Index (MHI), Migraine Disability Assessment Questionnaire (MIDAS) total, MIDAS A, MIDAS B, Migraine Work and Productivity Loss Questionnaire-question 7 (MWPLQ7), and Migraine-Specific Quality of Life Questionnaire (MSQ) version 2.1 were used to evaluate functional outcomes. Patients were evaluated prior to treatment and at 1, 2, and 2.5 years after treatment. Results: A total of 44 patients were included in the study (surgery=33, BTA=11). Patients treated surgically showed statistically significant improvement in headache intensity as measured on MIDAS B (p = 0.0464) and reduced disability as measured on MWPLQ7 (p = 0.0120) compared to those treated with BTA injection. No statistical difference between groups was found for the remaining functional outcomes. Mean scores significantly improved over time independently of treatment for MHI, MIDAS total, MIDAS A, MIDAS B, and MWPLQ 7 (p<0.05). However, no difference in mean scores over time was observed for MSQ. Conclusions: Headache surgery and targeted BTA injections are both effective means of addressing peripheral trigger sites causing headache pain. However, lower pain intensity and work-related disabilities were found in the surgical group.

Effect of Pranayama as Adjuvant to Medical Treatment on Severity, Frequency, and Duration of Headache in Migraine Patients: An Open-Label Randomized Controlled Trial.

Background: Migraine is the second leading cause of disability worldwide with high rates of dissatisfaction for allopathic treatment among patients. Pranayama is an easy, convenient, and cost-effective method that can supplement existing standard medical treatment of migraine. Objective: To study the effect of pranayama as an adjuvant to standard medical treatment of migraine on clinical outcome variables of migraine. Materials and Methods: This was a randomized controlled trial conducted on 80 consecutive migraine patients who were diagnosed as per International Classification of Headache Disorders-3 (ICHD-3) criteria and were randomly allocated into two groups, that is, standard medical treatment (SMT) group and standard medical treatment plus pranayama (SMT + P) group. The effect of pranayama on clinical outcome variables of migraine was evaluated by using standardized questionnaires. The data was statistically analyzed using SPSS Statistics 20 software. A P value of ≤0.05 was considered statistically significant. Results: Intragroup analysis showed all clinical outcome variables of migraine reduced significantly in the SMT + P group whereas all clinical outcome variables of migraine except the duration of headache episodes reduced significantly in the SMT group. Although statistically non-significant, intergroup analysis demonstrates that reduction in headache severity, duration of headache episodes, and headache impact test-6 (HIT-6) score was more in the SMT + P group whereas reduction in headache frequency and migraine disability assessment (MIDAS) score was more in the SMT group. Conclusion: Pranayama supplements the standard medical treatment of migraine by reducing the duration of headache episodes in addition to the reduction in headache severity, headache frequency, HIT-6 scores, and MIDAS scores.

Completing genome replication outside of S phase.

Mitotic DNA synthesis (MiDAS) is an unusual form of DNA replication that occurs during mitosis. Initially, MiDAS was characterized as a process associated with intrinsically unstable loci known as common fragile sites that occurs after cells experience DNA replication stress (RS). However, it is now believed to be a more widespread "salvage" mechanism that is called upon to complete the duplication of any under-replicated genomic region. Emerging data suggest that MiDAS is a DNA repair process potentially involving two or more pathways working in parallel or sequentially. In this review, we introduce the causes of RS, regions of the human genome known to be especially vulnerable to RS, and the strategies used to complete DNA replication outside of S phase. Additionally, because MiDAS is a prominent feature of aneuploid cancer cells, we will discuss how targeting MiDAS might potentially lead to improvements in cancer therapy.

Do climate policy uncertainty and investor sentiment drive the dynamic spillovers among green finance markets?

Green finance is an essential instrument for improving the environment and addressing climate change. This study investigates the dynamic spillovers among green finance markets using time-varying parameter vector autoregression (TVP-VAR) spillover indices, and further investigates the impact of climate policy uncertainty and investor sentiment on spillovers based on the generalised autoregressive conditional heteroscedasticity mixed data sampling (GARCH-MIDAS) model. The results indicate that: (i) environmental, social and governance (ESG), clean energy and water markets are information transmitters in the green finance system, whereas green building, green transportation, green bond and carbon markets are mainly information receivers; (ii) green stock markets including clean energy, non-energy and ESG markets transmit and receive greater information in the green finance system, while green bond and carbon markets do less; (iii) the green bond market is more interconnected with other green finance markets after the COVID-19 outbreak; (iv) investor sentiment contributes more to the net total directional spillovers of green resource markets (water and clean energy), while climate policy uncertainty contributes more to total spillovers and the net total directional spillovers of other green finance markets. These findings offer invaluable guidance for both policymakers and environmental investors.

Study of severe migraine in general medicine.

OBJECTIVE: To evaluate the criteria of severe migraine in a general population consulting a general practitioner (GP) and to evaluate assessment of migraine severity in the migraine patient as well as treating physicians' knowledge of their patient's migraine and its severity. METHODS: We questioned voluntary headache patients who had an appointment with a GP about the severity of their migraine using recognized scores - HIT-6 and MIDAS - as well as with a specific questionnaire created for the study. We compared the criteria for severe migraine with the patient's description of their symptoms, their HIT-6 score, their MIDAS score, and the GP's opinion, analyzing collected data using means and standard deviations. RESULTS: We found that 152 out of 942 headache patients questioned in the general medicine setting met the criteria of "strict migraine", corresponding to 10.3% prevalence. Seventy-one out of 100 patients (71%) with migraine who filled out in the questionnaire completely had what is characterized as "severe migraine". Forty-one (57%) of the 71 severe migraine patients presented the strict criteria. Additionally, 21 of the 29 (72%) patients with a non-severe diagnosis agreed that their headache was non-severe. When the HIT-6 score was stratified above 65, correspondence between the questionnaire-derived diagnosis and patient perception of severity was observed in 36 of the 58 (62%) with severe migraine. Finally, participating GPs were aware of their patient's migraine for 60% of patients with migraine. GPs correctly classified the severity of their patient's migraine for 55 (36%) patients. CONCLUSION: GP education and training about migraine remain a public health issue. The diagnosis of severe migraine is necessary for proper patient management. Current criteria for severe migraine are not robust enough; we propose a modification of the criteria.

High-frequency monitoring of China's green growth-at-risk.

With industrialization and urbanization, China faces enormous challenges from energy security and environmental issues. To address these challenges, it is imperative to establish a green accounting system for economic growth and to measure the uncertainty of China's green GDP (GGDP) growth from a risk management perspective. With this in mind, we follow the idea of growth-at-risk (GaR) to propose the concept of green GaR (GGaR) and extend it to the mixed-frequency data environment. Specifically, we first measure China's annual GGDP using the System of Environmental Economic Accounting (SEEA), then construct China's monthly green financial index by a mixed-frequency dynamic factor model (MF-DFM), and finally monitor China's GGaR from 2008M1 to 2021M12 with the mixed data sampling-quantile regression (MIDAS-QR) method. The main findings are as follows: First, the proportion of China's GGDP to traditional GDP gradually increases from 81.97% in 2008 to 89.34% in 2021, which illustrates that the negative environmental externalities caused by China's economic growth are gradually decreasing. Second, the high-frequency GGaR has favorable predictive performance and is significantly superior to the common-frequency GGaR at most quantiles. Third, the high-frequency GGaR has good nowcasting performance, and its 90% and 95% confidence intervals include true value for all prediction horizons. Furthermore, it can provide early warning of economic downturns through probability density prediction. Overall, our main contribution lies in constructing a quantitative assessment and high-frequency monitoring of China's GGDP growth risk, which provides an effective tool for investors and companies to predict risk, and a reference for the Chinese government to better formulate sustainable development strategies.

Two-year, real-world erenumab persistence and quality of life data in 82 pooled patients with abrupt onset, unremitting, treatment refractory headache and a migraine phenotype: New daily persistent headache or persistent post-traumatic headache in the majority of cases.

BACKGROUND: Patients diagnosed with New Daily Persistent Headache and Persistent Post-Traumatic Headache belong to a heterogeneous group of primary and secondary headache disorders, with the common clinical feature that these conditions start abruptly, continue unabated, and are refractory to conventional migraine preventive treatments. OBJECTIVE: This is a real-world, medium-term audit to explore whether erenumab improves quality of life in a pooled group of 82 abrupt-onset, unremitting and treatment refractory patients, where the diagnosis is new daily persistent headache and persistent post-traumatic headache in the majority of cases. METHODS: Eighty-two patients were treated with erenumab every 28 days over a two to three-year period, beginning in December 2018. These patients were "longstanding chronic" and refractory with a median of eight (IQR 4-12) prior failed migraine preventive treatments and median duration of disease of seven (IQR 3-11) years. The starting dose of erenumab was 70 mg in 79% of cases and 140 mg in the remaining patients (individuals with a BMI of more than 30). All patients were asked to complete three migraine specific Quality of Life questionnaires or Patient Reported Outcome Measures before starting treatment and typically at 3-12 intervals until the end of June 2021 or cessation of treatment. The Patient Reported Outcome Measures included: Headache Impact Test-6, Migraine Associated Disability Assessment test and Migraine-Specific Quality-of-Life Questionnaire. Patients generally only stayed on treatment after 6-12 months if there was deemed to be an improvement of at least 30% and there were no significant side effects. The longest treated cases have quality of life data for 30 months after starting erenumab. RESULTS: Of the 82 patients, 29 (35%) had improvement in Quality of Life scores, with no significant side effects, and wished to stay on treatment. Fifty-three patients (65%) stopped treatment during the first 6-25 months due to lack of efficacy and/or patient reported side effects (n = 33 and n = 17, respectively) or a combination of both, pregnancy planning (n = 2), and lost to follow up (n = 1). CONCLUSION: Significant improvements in Quality of Life scores were recorded by one-third of patients over a period of 11-30 months, with a 35% persistence after a median of 26 months of treatment. This contrasts with our recently published, treatment resistant, chronic migraine cohort where the persistence with erenumab treatment was almost 55% after a median time of 25 months.

The impact of resilience on headache disability as measured by the Migraine Disability Assessment (MIDAS).

OBJECTIVE: Our objectives were to examine cross-sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. BACKGROUND: Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache-related disability as measured by the Migraine Disability Assessment (MIDAS). METHODS: We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS-25), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and WHO-5 Well-Being Index. RESULTS: The CDRS-25 score was negatively correlated with the total MIDAS (r = -0.21, p = 0.009), GAD-7 (r = -0.56, p < 0.001), and PHQ-9 scores (r = -0.34, p < 0.001). Well-being inversely correlated with disability (r = -0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS-25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS-25 score did not significantly moderate the association between headache days and disability. CONCLUSION: Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache.