The variability of diagnosed migraine epidemiology amongst different municipalities in southern Israel.

BACKGROUND: Appropriate and timely diagnosis is one of the most important milestones in effective migraine care and is affected by public awareness, access to medical care, health care systems, and physicians' knowledge. We assessed the variability in migraine diagnosis rates in different communities under universal national health coverage in Israel. METHODS: In this population-based retrospective, observational, cohort study, adult (≥18 years) migraine patients were identified in the computerized database of the southern district of the Clalit Health Services Health Maintenance Organization (HMO) based on recorded diagnosis and/or purchase of specific anti-migraine acute medication (triptans). Migraine prevalence in 2018 was calculated in the entire study population and in different municipalities. We utilized a standardized (age and gender) mortality ratio (SMR) approach for comparison among the municipalities. RESULTS: In 2018, a total of 29,938 migraine patients were identified out of 391,528 adult HMO members, with an overall prevalence (per 10,000) of migraine of 764.64 (7.65%), 1143.34 (11.43%) for women, and 374.97 (3.75%) for men. Among the municipalities, adjusted prevalence (per 10,000) ranged from 386.15 (3.86%) to 1320.60 (13.21%). The female-to-male ratio ranged from 1.8:1 to 5.1:1. Prevalence rates were positively associated with the socioeconomic status of the municipalities (Spearman rho = 0.472, P = 0.031). CONCLUSIONS: High variability in the prevalence of diagnosed migraine suggests underdiagnosis. Resources for awareness and educational programs should be directed to low diagnosed prevalence communities.

Migraine epidemiology and comorbidities in Southern Israel: a clinical database study in a universal health coverage setting.

BACKGROUND: Understanding migraine epidemiology and its burden is crucial for planning health policies and interventions at the local level as well as at the global level. National policies in Israel rely on global estimations and not on local data since local epidemiologic studies had not previously been performed. In this study, we evaluated the epidemiology of migraine in the southern district of Israel using the electronic medical records database of the largest Israeli health maintenance organization (HMO). METHODS: In this population-based, retrospective, observational cohort study, adult migraine patients were identified in the computerized database of the southern district of the Clalit Health Services HMO (total population, 0.75 million). Patients were identified based on recorded diagnosis (International Classification of Diseases, Ninth Revision) and/or claims for specific anti-migraine medication (triptans) between 2000 and 2018. A 1:2 age-, gender-, and primary care clinic-matched control group was used for evaluation of comorbidities. RESULTS: In 2018, a total of 29,938 patients with migraine were identified out of 391,528 adult HMO members. Most of the patients were women (75.8%), and the mean ± standard deviation age at diagnosis was 36.94 ± 13.61 years. The overall prevalence of migraine (per 10,000) was 764.64 (7.65%), 1143.34 (11.43%) for women and 374.97 (3.75%) for men. The highest prevalence was observed in patients aged 50 to 60 years and 40 to 50 years (1143.98 [11.44%] and 1019.36 [10.19%], respectively), and the lowest prevalence was among patients aged 18 to 30 years and > 70 years (433.45 [4.33%] and 398.49 [3.98%], respectively). CONCLUSIONS: This is the first large-scale epidemiologic study of migraine prevalence in Israel. Compared to international estimations, migraine appears to be underdiagnosed in the southern district of Israel.

Burden of migraine in Brazil: A cross-sectional real-world study.

OBJECTIVE: To assess the burden and consequences of migraine in Brazil in terms of health-related quality of life (HRQoL), work productivity and daily activities, and healthcare resource utilization (HRU). BACKGROUND: Despite existing data on how migraine affects populations worldwide, there are limited data on the burden of migraine in Latin America. METHODS: This cross-sectional study used patient-reported data from the 2018 Brazil National Health and Wellness Survey. HRQoL scores (EuroQol 5-dimension 5-level [EQ-5D-5L]; 36-item Short Form Health Survey, version 2 [SF-36v2]; and Short Form 6-dimension [SF-6D]), impairments to work productivity and daily activities (Work Productivity and Activity Impairment questionnaire), and all-cause HRU were compared between migraine respondents and matched non-migraine controls. RESULTS: Of the 12,000 total respondents in the survey database, 1643 self-reported a physician diagnosis of migraine and were propensity score matched 1:1 with controls without migraine. HRQoL was lower in patients with migraine versus non-migraine controls, with significantly lower SF-36v2 physical (mean [± SD] 50.3 [7.5] vs. 52.0 [7.6]) and mental component (mean [± SD] 42.9 [10.2] vs. 46.0 [9.9]) summary scores and SF-6D (mean [± SD] 0.7 [0.1] vs. 0.7 [0.1]) and EQ-5D-5L (mean [± SD] 0.7 [0.2] vs. 0.8 [0.2]) utility scores (all p < 0.001). Patients with migraine reported higher levels of work productivity loss (mean [± SD], 40.6% [31.4%] vs. 28.6% [30.9%], including absenteeism 12.8% [19.1%] vs. 8.4% [17.1%] and presenteeism 35.0% [28.7%] vs. 24.8% [28.0%]; all p < 0.001); activity impairment (mean [± SD] 36.0% [28.8%] vs. 25.5% [28.1%]; p < 0.001); and significantly higher HRU in the past 6 months (healthcare provider and emergency department visits [mean [± SD] 7.2 [9.5] vs. 4.5 [6.3] and 1.7 [3.8] vs. 0.9 [2.2]; both p < 0.001] and hospitalizations [mean [± SD] 0.4 [2.7] vs. 0.2 [1.1]; p = 0.002]) than controls. CONCLUSION: Migraine is associated with poorer HRQoL, higher all-cause HRU, and greater activity impairment and work productivity loss versus non-migraine controls in Brazil.

Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers.

How the numbers of niches and resident stem cells within a particular organ are determined during development and how they may be modulated or corrected is a question with significant medical implications. In the larval ovary of Drosophila melanogaster, somatic precursors for niches, and germ cells that will become germline stem cells, co-develop. Somatic precursors proliferate during the first 3 days of larval development. By mid-third instar, adult terminal filament (TF) (part of the germline stem cell niche) cells first appear, and differentiation terminates 24 h later when 16-20 TFs fully form. The developmental sequence responsible for TF cell determination and final TF numbers is only partially understood. We show that TF formation proceeds through several, hitherto uncharacterized stages, which include an early exit from the cell cycle to form TF precursors and two steps of cell shape change to form the mature TF cells. The Activin receptor Baboon (Babo) is required for somatic precursor cell proliferation and therefore determines the pool of TF precursors available for TF differentiation. During the final differentiation stage, Babo facilitates TF and germ cell differentiation, and promotes the accumulation of Broad-Z1, which is also a target of the steroid hormone ecdysone. Epistasis analysis shows that Activin controls cell proliferation in an ecdysone-independent manner and TF differentiation by affecting ecdysone targets. We propose that this mode of function allows Activin to balance proliferation and differentiation, and to equilibrate niche numbers. These results suggest a novel model for how niche numbers are corrected during development.

Coordinated regulation of niche and stem cell precursors by hormonal signaling.

Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis. How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown. In fruit flies, primordial germ cells (PGCs), the precursors of germ line stem cells (GSCs), and somatic niche precursors develop within the larval ovary. Together they form the 16-20 GSC units of the adult ovary. We show that ecdysone receptors are required to coordinate the development of niche and GSC precursors. At early third instar, ecdysone receptors repress precocious differentiation of both niches and PGCs. Early repression is required for correct morphogenesis of the ovary and for protecting future GSCs from differentiation. At mid-third instar, ecdysone signaling is required for niche formation. Finally, and concurrent with the initiation of wandering behavior, ecdysone signaling initiates PGC differentiation by allowing the expression of the differentiation gene bag of marbles in PGCs that are not protected by the newly formed niches. All the ovarian functions of ecdysone receptors are mediated through early repression, and late activation, of the ecdysone target gene broad. These results show that, similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis in insects. They further exemplify how a physiological cue coordinates the formation of a stem cell unit within an organ: it is required for niche establishment and to ensure that precursor cells to adult stem cells remain undifferentiated until the niches can accommodate them. Similar principles might govern the formation of additional stem cell units during organogenesis.