Occurrence of new or more severe headaches following COVID-19 is associated with markers of microglial activation and peripheral sensitization: results from a prospective cohort study.

BACKGROUND: New onset or worsening of a headache disorder substantially contributes to the disease burden of post-COVID-19. Its management poses a suitable means to enhance patients' participation in professional, social, and personal activities. Unfortunately, the pathophysiology of post-COVID-19 headaches is poorly understood. This study aims to investigate the role of (neuro-) inflammatory mechanisms in order to guide the development of anti-inflammatory treatment strategies. METHODS: We included patients from the interdisciplinary post-COVID-19 Rehabilitation Study (PoCoRe, n = 184 patients) run at a tertiary care university hospital, comprising patients with PCR-confirmed SARS-CoV-2 infection ≥ 6 weeks prior to their initial consultation. Patients reporting any headache since their infection were considered for this study (n = 93). These were interviewed and classified according to the International Classification of Headache Disorders, Third Edition (ICHD-3) by headache specialists. Patient sera were additionally analysed for levels of VILIP-1, MCP-1 (CCL2), sTREM-2, BDNF, TGF-ß1, VEGF, IL-6, sTREM-1, ß-NGF, IL-18, TNF-alpha, sRAGE, and CX3CL1 (Fractalkine). Markers of inflammation were compared between four groups of patients (none, unchanged, worsened, or new headache disorder). RESULTS: Patients reported experiencing more severe headaches (n = 17), new onset headaches (n = 46), unchanged headaches (n = 18), and surprisingly, some patients denied having any headaches (n = 12) despite self-reports. Serum levels of CX3CL1 were increased in the worsened (2145 [811-4866] pg/ml) and new onset (1668 [0-7357] pg/ml) headache group as compared to patients with no (1129 [0-5379] pg/ml) or unchanged (1478 [346-4332] pg/ml) headaches. Other markers also differed between groups, but most significantly between patients with worsened (TGF-ß1: 60 [0-310] pg/ml, VEGF: 328 [86-842] pg/ml, ß-NGF: 6 [3-38] pg/ml) as compared to unchanged headaches (TGF-ß1: 29 [0-77] pg/ml, VEGF: 183 [72-380] pg/ml, ß-NGF: 3 [2-89] pg/ml). The results did not differ between headache phenotypes. DISCUSSION: This study provides evidence that worsened or new headaches following COVID-19 are associated with pro-(neuro-)inflammatory profiles. This supports the use of anti-inflammatory treatment options in this population, especially in the subacute phase.

Autonomic dysfunction syndrome in pregnant women.

Available studies and information on the regulatory effect of the autonomic nervous system (ANS) in pregnancy are insufficient and contradictory due to a variety of research methods of ANS, the lack of a single standardized approach to the assessment of the functional tone of the ANS departments, and interpretation of the results. The aim of the study is investigation and predictive assessment of clinical and laboratory data in pregnant women with suprasegmental autonomic dysfunction with or without hypertension to determine the main directions of effective prevention of the nervous system damage. The material of the study included 206 pregnant women diagnosed with the syndrome of autonomic dysfunction in different variants. Age ranged from 17 to 47 years. All pregnant women had the following laboratory tests: general clinical tests, biochemical blood tests, including prothrombin index, fibrinogen, von Willebrand factor activity. The clinical and laboratory data were analyzed in pregnant women with autonomic dysfunction with or without hypertension. According to the results, it was found that in all groups of pregnant women a sympathetic effect prevails. This study showed that in the group of normotensive pregnant women, the main symptom is venous dysfunction, which poses a risk of an adverse course of cerebrovascular disease.

Clinico-radiological profile of CVT patients and its correlation with D-dimer.

Cerebral Venous Thrombosis (CVT) is a well-known disease with diverse clinical presentation and causes. With advances in neuroimaging and changing lifestyles, the clinical profile and causes of CVT are changing. D-dimer has been studied in early diagnosis of CVT with variable results. This prospective study was carried out to assess the clinical profile of CVT and role of D-dimer in early diagnosis of CVT. The study period was from September 2017 to July 2019 and included 32 imaging proven patients of CVT. We also included 32 patients of migraine for assessing D-dimer. Data was collected according to a preformed format. D-dimer was assessed by a rapid semi-quantitative latex agglutination assay. Out of 32 CVT patients, 16(50%) were females. The mean age of the patients was 31.56 ± 14.31 years. Most common clinical features were headache (96.25%), papilloedema (37.5%) and seizures 10 (31.25%). Puerperium was the most common cause of CVT in females. Superior sagittal and transverse sinuses were the most common sinuses to be affected. The sensitivity of D-dimer assay was 81.25% and specificity 62.5%. Cerebral venous thrombosis is a disease with equal predilection among both genders affecting mostly young individuals. Most of the patients present with headache. Puerperium still contributes to majority of the cases. Iron deficiency anaemia needs to be evaluated as an association for CVT. Positive D-dimer should strengthen the suspicion of CVT in patients with acute headache.

Effects of endurance exercise on serum concentration of calcitonin gene-related peptide (CGRP): a potential link between exercise intensity and headache.

Background Calcitonin gene-related peptide (CGRP) is a powerful neuropeptide that is strongly involved in headache pain pathogenesis by triggering vasodilation, mast cell degranulation and neurogenic inflammation. This evidence has prompted us to investigate the acute influence of endurance exercise on CGRP concentration in blood. Methods The study population consisted of 48 male amateur runners, who ran a half-marathon distance at 75%-85% of maximal oxygen uptake. Blood was drawn before the run (pre-run) and immediately after each runner ended his trial (post-run). The serum concentration of CGRP was measured with a commercial enzyme-linked immunosorbent assay (ELISA) technique. Results Overall, 22/48 subjects (45.8%) reported suffering from headache, three of whom (6.2%) had an exertional headache, whilst 26/48 (54.2%) subjects did not report at least one headache episode during the previous 6 months (i.e. headache-free). All 48 athletes successfully covered the 21.1 km distance. Serum concentration of CGRP significantly increased by 1.5-fold in the entire group, as well as in the headache-positive and headache-free cohorts. Univariate Spearman's correlation revealed that post-run variation of serum CGRP was significantly and inversely associated with running time (r = -0.30; p = 0.036). Conclusions The serum concentration of CGRP is significantly enhanced by medium-distance endurance exercise and the post-exercise increase is dependent on running intensity. Accordingly, high-exercise intensity might be directly related to triggering both exertional headache and/or migraine episodes.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients.

METHODS: Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. RESULTS: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. CONCLUSION: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

The Role of Vitamin D in Primary Headache-from Potential Mechanism to Treatment.

Some studies have suggested a link between vitamin D and headache; however, the underlying physiological mechanisms are unclear. We aimed to summarize the available evidence on the relationship between vitamin D and the various subtypes of primary headaches, including migraines and tension-type headaches. All articles concerning the association between primary headache and vitamin D published up to October 2019 were retrieved by searching clinical databases, including: EMBASE, MEDLINE, PubMed, Google scholar, and the Cochrane library. All types of studies (i.e., observational, cross-sectional, case-control, and clinical trials) were included. We identified 22 studies investigating serum vitamin D levels in association with headaches. Eight studies also evaluated the effect of vitamin D supplementation on the various headache parameters. Among them, 18 studies showed a link between serum vitamin D levels and headaches, with the strongest connection reported between serum vitamin D levels and migraine. Overall, there is not enough evidence to recommend vitamin D supplementation to all headache patients, but the current literature indicates that it may be beneficial in some patients suffering headaches, mainly migraineurs, to reduce the frequency of headaches, especially in those with vitamin D deficiency.

Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial.

INTRODUCTION: Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs. METHODS AND MATERIALS: This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 µg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method. RESULTS: At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055). CONCLUSION: Based on the results of this study, we found that 2000 IU (50 µg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients / Resolução de cefaleia após redução dos níveis de prolactina em pacientes com hiperprolactinemia

Abstract Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. Methods: The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resumo Os adenomas secretores de prolactina (PRL) estão associados à alta incidência de cefaleia. O papel da hiperprolactinemia no contexto da dor de cabeça não está claro, nem o efeito da redução dos níveis da PRL na cefaleia. Métodos: O presente estudo longitudinal avaliou pacientes hiperprolactinêmicos (69), quanto à presença e às características da cefaleia antes e após o tratamento da hiperprolactinemia. Resultados: Cefaleia foi relatada por 45 (65,2%) pacientes, independente da etiologia da hiperprolactinemia. O fenótipo de enxaqueca foi mais prevalente (66,6%). Os medicamentos usados ​​no tratamento da cefaleia não foram alterados durante o estudo. A primeira linha de tratamento da hiperprolactinemia foram os agonistas dopaminérgicos. Na última reavaliação, o nível de PRL sob tratamento estava dentro da faixa de referência em 54,7% dos casos, observando-se resolução completa ou parcial da cefaleia em 75% dos casos. A mediana de PRL neste momento em pacientes com resolução completa da cefaleia foi de 17 ng/mL, nos que relataram recuperação parcial foi de 21 ng/mL, e naqueles em que a cefaleia não se alterou foi de 66 ng/mL, com uma diferença significativa entre o grupo com resolução completa da cefaleia versus o grupo com cefaleia inalterada (p=0,022). Nos casos com resolução completa da cefaleia, a queda mediana nos níveis de PRL foi de 89% e nos casos com resolução parcial de cefaleia de 86%, ambos significativamente diferentes (p<0,001) da queda nos casos com cefaleia inalterada. Conclusão: Os dados permitem concluir que, nesta série, na maioria dos casos, a redução do nível de PRL foi seguida pela cessação ou alívio da dor.

Diagnostic Value of D-dimer in Distinguishing between Spontaneous Subarachnoid Hemorrhage and Nontraumatic Acute Headache.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SSAH) and nontraumatic acute headache patients presented with symptoms similar to headache. This study was to investigate the diagnostic value of D-dimer (DD) in distinguishing patients with SSAH from those with nontraumatic acute headache. METHODS: This retrospective study was performed and data were gathered from medical records of patients with acute headache symptoms from the Emergency Department and Neurology Clinics who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between January 2015 and January 2019. Of the total 114 patients with headache symptoms enrolled in this study, 46 patients were diagnosed with SSAH (SAH group) and 68 cases with nontraumatic acute headache due to other causes (non-SAH group). The plasmatic levels of PT, INR, APTT, TT, FIB, and DD were compared between the two groups. Student's t-test of independent samples was adopted for comparing the mean between the two groups. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed using the Z-test. RESULTS: There were no significant statistical differences of the PT, INR, TT and FIB (all p > 0.05). The APTT was significantly decreased in the SSAH group compared with non-SAH group, while DD was significantly increased (all p < 0.001); moreover, AUC in distinguishing patients with SSAH from those with nontraumatic acute headache was 0.721 (95% confidence interval (CI), 0.629 to 0.801) for APTT and 0.886 (95% CI, 0.813 to 0.938) for DD. There was a significant statistical difference (p < 0.01). Finally, the cutoff values were 25.2s in distinguishing patients with SSAH from those with nontraumatic acute headache (specificity 73.53% and sensitivity 60.87%) for APTT and 0.31 mg/L (specificity 83.82% and sensitivity 84.78%) for DD. CONCLUSIONS: As an easy-to-obtain and potential biomarker, DD could demonstrate more accurate and reliable diagnostic value than APTT in distinguishing between SSAH and nontraumatic acute headache.

Comparison of the Diagnostic Values of Neutrophil, Neutrophil to Lymphocyte Ratio, and Platelet to Lymphocyte Ratio in Distinguishing Spontaneous Subarachnoid Hemorrhage from Nontraumatic Acute Headache.

BACKGROUND: To compare the diagnostic values of neutrophil, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) in distinguishing between spontaneous subarachnoid hemorrhage (SSAH) and non-traumatic acute headache. METHODS: Of the 125 patients with headache symptoms, 54 patients were diagnosed with SSAH (SAH group) and 71 cases with nontraumatic acute headache due to other causes (non-SAH group) were enrolled in this retrospective study. The levels of peripheral blood neutrophil counts, lymphocyte counts, platelet counts, NLR and PLR were recorded and compared between two groups. Student's t-test of independent samples was adopted for comparing the mean between two groups. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed using the Z-test. RESULTS: The levels of neutrophil counts, NLR and PLR were significantly increased in the SSAH group compared with the non-SAH group (all p < 0.01), while there were no significantly statistical differences of the lymphocyte counts and platelet counts (all p > 0.05); moreover, AUC in distinguishing between SSAH and nontraumatic acute headache was 0.918 (95% confidence interval (CI), 0.855 to 0.960) for neutrophil counts, 0.828 (95% CI, 0.751 to 0.890) for NLR and 0.616 (95% CI, 0.524 to 0.701) for PLR, and there were significant statistical differences (all p < 0.05) after pairwise comparison. Finally, the cutoff values were 4.7 x 109/L in distinguishing patients with SSAH from those with nontraumatic acute headache (specificity 88.73%, sensitivity 85.19% and Youden index 0.739) for neutrophil counts, 4 (specificity 98.59%, sensitivity 64.81% and Youden index 0.634) for NLR and 175 (specificity 92.96%, sensitivity 44.44% and Youden index 0.374) for PLR. CONCLUSIONS: Neutrophils can demonstrate more accurate and reliable diagnostic value than NLR and PLR, sug-gesting that it is a useful and potential tool in distinguishing between SSAH and nontraumatic acute headache.

Intrinsic Coagulation Pathway, History of Headache, and Risk of Ischemic Stroke.

Background and Purpose- Hypercoagulable states in migraine patients may play a role in the pathophysiology underlying the association between migraine and ischemic stroke. This study aims to provide more insight into the potential association of headache, ischemic stroke, and the intrinsic coagulation pathway. Methods- We included patients from the RATIO study (Risk of Arterial Thrombosis in Relation to Oral Contraceptives), a Dutch population-based case-control study including young women (age <50) with ischemic stroke and healthy controls. We defined a headache group based on a questionnaire on headache history. Intrinsic coagulation proteins were measured through both antigen levels (FXII, FXI, prekallikrein, HK [high molecular weight kininogen]) and protein activation, determined by measuring activated protein complex with C1esterase-inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin-inhibitor (FXIa-AT-INH). We calculated adjusted odds ratios and performed an interaction analysis assessing the increase in stroke risk associated with high levels of intrinsic coagulation and history of headache. Results- We included 113 ischemic stroke cases and 598 healthy controls. In total, 134 (19%) patients had a history of headache, of whom 38 were cases and 96 controls. The combination of headache and high intrinsic coagulation protein levels (all but FXII antigen level and both FXIa-inhibitors) was associated with an increase in ischemic stroke risk higher than was expected based on their individual effects (adjusted odds ratio FXI antigen level alone: 1.7, 95% CI, 1.0-2.9; adjusted odds ratio headache alone: 2.0, 95% CI, 1.1-3.7; combination: 5.2, 95% CI, 2.3-11.6) Conclusions- Headache and high intrinsic coagulation protein levels may biologically interact, increasing risk for ischemic stroke.

A prospective study of headache and neuropeptides in patients with pituitary adenomas.

OBJECTIVE: To evaluate clinical criteria for headache associated with pituitary adenoma (HaPA) in the International Classification of Headache Disorders (ICHD) 3rd edition version criteria and further determine whether elevations of plasma calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide 1-38 (PACAP1-38) concentration contribute to HaPA. METHODS: Demographic and clinical features of consecutive patients with pituitary adenoma were recorded. Plasma calcitonin gene-related peptide and PACAP1-38 concentrations in pituitary adenoma patients within 72 h pre- and post-operation were measured. Primary outcome for HaPA patients were 50% reduction of moderate-to-severe headache days at 3 months after discharge. RESULTS: Sixty-three patients with pituitary adenoma were recruited, 33 (52.4%) of whom had headache. The patients who had HaPA presented with migraine-like (32.9%), tension-type-like (12.1%), and stabbing headache (9.1%). Non-functional adenoma was present in the majority of cases (82.5%). Surgical resection improved headache in 83.3% of cases at 3 month follow-up. Pre- and post-operative calcitonin gene-related peptide and PACAP1-38 levels were significantly higher in patients with headache than in those without headache (p < 0.05). Plasma calcitonin gene-related peptide and PACAP1-38 levels at 72 h post-operation were lower at 72 h after operation in patients who had greater improvement in headache compared with those who had little improvement, while plasma calcitonin gene-related peptide and PACAP1-38 levels were similar between these two groups preoperatively. CONCLUSIONS: Most pituitary adenoma patients have non-functional adenoma, and half of this group have HaPA, indicating that the ICHD-3 criteria for HaPA with the emphasis on secretion status need further modifications. Lower plasma calcitonin gene-related peptide and PACAP1-38 concentrations at 72 h after operation may predict a better outcome in patients with HaPA.

Effects of Phyllanthus amarus PHYLLPROTM leaves on hangover symptoms: a randomized, double-blind, placebo-controlled crossover study.

CONTEXT: Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown. OBJECTIVE: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms. MATERIAL AND METHODS: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21-50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS). RESULTS: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p < 0.0001). For HSS, the active group showed reduced hangover symptoms while there were higher levels of nausea, headache, anorexia, tremulousness, diarrhoea and dizziness in the placebo group (p < 0.05) at hour 10 post-intoxication. Increased fatigue at hour 2 and tension (p > 0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™. DISCUSSION AND CONCLUSION: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted.

First report of human ehrlichiosis in Turkey.

Emiroglu M, Çelebi B. First report of human ehrlichiosis in Turkey. Turk J Pediatr 2019; 61: 267-270. Ehrlichiosis, a tick-borne infection, can cause severe and fatal disease. A 6-year-old boy was admitted with fever, chills, malaise, headache, anorexia, rhinorrhoea, and cough lasting two days. He had had contact with a dog 10 days prior, and a tick had been removed the day before. Fever, minimal conjunctival injection, oropharyngeal hyperemia and cracked, hyperemic lips were observed. Laboratory tests were normal except for lymphopenia and hyponatremia. Cytoplasmic morulae in the monocytes and granulocytes were seen on peripheral blood smear. Doxycycline was started immediately, and the fever subsided within 48 hours. Given the Ehrlichia was positive but Anaplasma negative by real-time PCR, he was diagnosed as ehrlichiosis, subspecies identification could not be performed. This is the first human ehrlichiosis case in Turkey.

A study of clinical, hematological, and biochemical profiles of patients with dengue viral infections in Northwest Ethiopia: implications for patient management.

BACKGROUND: Dengue is one of the most common arboviral diseases with increased outbreaks annually in tropical and subtropical areas. In Ethiopia, there are no data regarding clinical, hematological and biochemical parameters which are very important in the clinical management of dengue patients. Hence this study was carried out to provide the first baseline data of clinical, hematological and biochemical profiles of patients infected with dengue virus. METHODS: A cross-sectional study was carried out among febrile patients in northwest Ethiopia from March 2016 to May 2017. Blood samples were collected from dengue presumed cases and tested against dengue specific IgM antibody by enzyme-linked immunosorbent assay (ELISA). Those study participants who fulfilled the inclusion criteria were enrolled in the study. Clinical examination findings were recorded, hematological and biochemical parameters tests were done. RESULTS: During the study period, a total of 102 dengue cases were included in the study. Of these, there were 16 (15.7%) children and 86 (84.3%) adults between 1 and 76 year age. The most common clinical presentations followed by fever (100%) were a headache 89 (87.3%), myalgia 82 (80.4%), nausea/vomiting 71 (69.6%). The common hematological findings were thrombocytopenia 61 (59.8%), followed by anemia 45 (44.1%) and leucopenia 27 (26.5%) and the elevated levels of biochemical parameters were AST 46 (45.1%) and ALT in 18 (17.6%). CONCLUSIONS: This study highlights the most common clinical and laboratory profiles of dengue viral infections that could alert physicians to the likelihood of dengue virus infections in the study area.

Safety, Tolerability, and Pharmacokinetics of the Novel Anti-influenza Agent Baloxavir Marboxil in Healthy Adults: Phase I Study Findings.

BACKGROUND AND OBJECTIVE: Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. This first-in-human phase I study evaluated the safety, tolerability, and pharmacokinetics of baloxavir marboxil/baloxavir acid in healthy Japanese volunteers (Study 1), while food effects were evaluated in a separate phase I, crossover study in healthy Japanese volunteers (Study 2). METHODS: Study 1 participants were randomized to single-dose oral baloxavir marboxil (6, 20, 40, 60, or 80 mg; n = 6 per dose) or placebo (n = 10), while Study 2 participants (n = 15) received single-dose oral baloxavir marboxil 20 mg in fasted, fed, and before-meal states. RESULTS: Baloxavir marboxil was well tolerated; there were few treatment-emergent adverse events and no serious adverse events/deaths. The mean plasma baloxavir acid concentration 24 h after single-dose (C24) oral baloxavir marboxil 6 mg was 6.92 ng/mL, exceeding the target C24 (6.85 ng/mL) estimated in nonclinical studies. In Study 1, baloxavir acid exposure demonstrated dose-proportional increases in the fasted state, with maximum plasma concentration generally attained within 3.5 h. Terminal elimination half-life ranged from 49 to 91 h. In Study 2, exposure was decreased and apparent clearance increased in the fed and before-meal states versus the fasted state; however, exposure exceeded the target C24 in all states. CONCLUSION: Single-dose oral baloxavir marboxil was well tolerated, had a favorable safety profile, and had favorable pharmacokinetic characteristics, including a long half-life, supporting single oral dosing. The baloxavir acid area under the plasma concentration-time curve decreased with food intake by approximately 40%.

Feasibility of serum CGRP measurement as a biomarker of chronic migraine: a critical reappraisal.

BACKGROUND: Calcitonin gene-related peptide (CGRP) has been reported as elevated in chronic migraine. We aimed to validate the role of interictal serum CGRP concentration in peripheral blood samples as a biomarker of chronic migraine. METHODS: We prospectively recruited patients with episodic and chronic migraine and normal controls (NCs) in the Samsung Medical Center between August 2015 and May 2016. Blood samples were collected interictally from antecubital veins per prespecified protocol. Serum CGRP measurement was performed in the central laboratory by a single experienced technician blinded to clinical information. Migraine subtype, headache days in the previous month, and the presence and characteristics of headache at ±2 days of measurement were evaluated at every visit. RESULTS: A total of 156 migraineurs (106 episodic and 50 chronic) and 27 NCs were recruited in this study. Compared to NCs (75.7 ± 20.07 pg/mL) and patients with episodic migraine (67.0 ± 20.70 pg/mL), patients with chronic migraine did not show an interictal elevation of serum CGRP levels (64.9 ± 15.32 pg/mL). Serum CGRP concentration was not associated with headache status (ictal vs. interictal), migraine subtype (migraine with vs. without aura), use of preventive or acute medications, and comorbid medication overuse. Higher serum CGRP concentration did not predict treatment response in patients with chronic migraine. CONCLUSIONS: Serum CGRP concentration may not be a feasible biomarker for chronic migraine. Further validation is necessary before CGRP can be used in the clinical practice.