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Background: Large conductance calcium-activated potassium (BKCa) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BKCa channel opener) could induce migraine-like headache in persons with PPTH. Methods: This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period. Results: Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P =.02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P <.001). Conclusions: Our results indicate that BKCa channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BKCa channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BKCa channel blockers in managing PPTH. ClinicalTrials.gov Identifier: NCT05378074. [ABSTRACT FROM AUTHOR]

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), known for its role in migraine pathogenesis, has been identified as a novel drug target. Given the clinical parallels between post-traumatic headache (PTH) and migraine, we explored the possible role of PACAP-38 in the pathogenesis of PTH. To this end, we conducted a randomized, double-blind, placebo-controlled, two-way crossover trial involving adult participants diagnosed with persistent PTH resulting from mild traumatic brain injury. Participants were randomly assigned to receive a 20-min continuous intravenous infusion of either PACAP-38 (10 pmol/kg/min) or placebo (isotonic saline) on two separate experimental days, with a 1-week washout period in between. The primary outcome was the difference in incidence of migraine-like headache between PACAP-38 and placebo during a 12-h observational period post-infusion. The secondary outcome was the difference in the area under the curve (AUC) for baseline-corrected median headache intensity scores during the same 12-h observational period. Of 49 individuals assessed for eligibility, 21 were enrolled and completed the trial. The participants had a mean age of 35.2 years, and 16 (76%) were female. Most [19 of 21 (90%)] had a migraine-like phenotype. During the 12-h observational period, 20 of 21 (95%) participants developed migraine-like headache after intravenous infusion of PACAP-38, compared with two (10%) participants after placebo (P < 0.001). Furthermore, the baseline-corrected AUC values for median headache intensity scores during the 12-h observational period was higher after PACAP-38 than placebo (P < 0.001). These compelling results demonstrate that PACAP-38 is potent inducer of migraine-like headache in people with persistent PTH. Thus, targeting PACAP-38 signalling might be a promising avenue for the treatment of PTH. [ABSTRACT FROM AUTHOR]

Background: Following the promising pre-marketing placebo-controlled randomized clinical trials of fremanezumab, post-marketing studies are necessary to verify efficacy and tolerability in various real-world settings. The present study assessed real-world efficacy and safety of fremanezumab. Methods: A 3-month, single-center, prospective, observation study of adults with chronic migraine who were treated with monthly subcutaneous injections of 225 mg fremanezumab in Denmark. The primary outcome was defined as proportion of patients who achieved =30% reduction in monthly migraine days (MMDs) from baseline to weeks 9-12. Among secondary outcomes were =50 and =75% responder rates and the proportion of patients reporting adverse events. Results: A total of 91 patients with chronic migraine were enrolled and received at least one dose of fremanezumab of whom 89 patients (98%) completed the 3-months treatment period. At baseline, the mean (SD) number of monthly headache days was 24.3 ± 5.8 and mean number of MMDs was 18.5 ± 7.4. The number of patients who achieved =30% reduction in MMDs from baseline to weeks 9-12 was 58 (65%), while 45 (51%) and 21 (24%) had =50 and 75% reduction in MMD, respectively. Twenty-one patients (23%) reported adverse event, in which the most common were constipation (4.4%), fatigue (4.4%) and dizziness (3.3%). No serious adverse events were reported. Conclusion: In adult chronic migraine patients with previous failure of conventional oral migraine preventives, fremanezumab was found to be effective and well-tolerated. [ABSTRACT FROM AUTHOR]

Background: Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population. Methods: The REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP. Results: The study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications. Conclusion: The REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article. Trial registration: The study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020). [ABSTRACT FROM AUTHOR]

Background: Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) provoked cluster headache attacks in individuals with episodic cluster headache during their active phase and individuals with chronic cluster headache. In this study, we investigated whether infusions of PACAP and VIP caused alterations in plasma levels of VIP and their potential contribution to induced cluster headache attacks. Methods: Participants received either PACAP or VIP infusion for 20min on 2 separate days with an interval of at least 7 days in between. Blood collection was performed at T0, T20, T30, and T90. Plasma levels of VIP were measured using a validated radioimmunoassay method. Results: Blood samples were collected from participants with episodic cluster headache in the active phase (eCHA, n = 14), remission (eCHR, n = 15), and from participants with chronic cluster headache (cCH, n = 15). Baseline levels of VIP did not differ among the three groups (p = 0.1161). During PACAP infusion, mixed-effects analysis revealed a significant increase in plasma levels of VIP in eCHA (p = 0.0300) and eCHR (p = 0.0058) but not in cCH (p = 0.2930). We found no difference in the increase of plasma VIP levels between patients who developed PACAP38- or VIP-induced attacks. Conclusion: Cluster headache attacks induced by PACAP38 or VIP infusion are not associated with changes in plasma levels of VIP. Further studies are needed to investigate the role of VIP and the parasympathetic system in cluster headache. [ABSTRACT FROM AUTHOR]

Antibodies blocking the calcitonin gene-related peptide have revolutionized episodic and chronic migraine treatment. However, their applicability to non-cephalic pain conditions, such as osteoarthritis, is yet unknown. Osteoarthritis remains a clinical challenge, associated with high disability and limited treatment options. Like migraine, neuropeptides including calcitonin gene-related peptides are involved in its pathophysiology. We present the first case of a patient: a 73-year-old female with osteoarthritis who received monthly treatment for her chronic migraine with 140 mg subcutaneous erenumab, a monoclonal antibody against the receptor of calcitonin gene-related peptide. Though the migraine was unresponsive, the patient's arthritic symptoms improved drastically during treatment period with erenumab; daily pain decreased from VAS 7 to 2, and walking distance doubled from 1,000 m to 2,000 m. The arthritic symptoms relapsed after discontinuation of erenumab. Erenumab could potentially have beneficial effects on symptoms of osteoarthritis. Future studies investigating these effects are warranted. [ABSTRACT FROM AUTHOR]

In clinical practice, patients with cluster headache often ask questions or mention information that they have seen or heard on the Internet. Because YouTube (www.youtube.com) is the second most visited Web site worldwide and offers a plethora of video content, we found it timely to ascertain the quality of information on cluster headache that is freely available on YouTube. We conducted an inquiry on YouTube on January 24, 2022, with the search term "cluster headache." Eligible YouTube videos included those with ≥10,000 views and content related to cluster headache. We assessed the quality and reliability of the videos with the Global Quality Scale and DISCERN, respectively. The search strategy identified 644 videos of which 134 were eligible for inclusion. The sources of the included videos were categorized as "healthcare professional/institution" (n = 45), "personal experience" (n = 52), and "other" (n = 37). According to the Global Quality Scale, 70 (52%) were low quality, 34 (25%) were of moderate quality, and 30 (22%) were of high quality. According to DISCERN, 104 (78%) were of low reliability, 28 (21%) were of moderate reliability, and 2 (1%) were of high reliability. The quality and reliability of cluster headache‐related information on YouTube has room for improvement, even the content provided by healthcare providers. These findings should incentivize stakeholders, for example, government services, professional societies, healthcare providers, to provide accessible and better information on cluster headache. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide can provoke cluster headache attacks in up to half of cluster headache patients in their active phase. At present, it is unknown whether provoked attacks are mediated via calcitonin gene-related peptide or mast cell activation. Methods: All enrolled patients with cluster headache were randomly allocated to receive a continuous infusion of either PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We collected clinical data and measured plasma levels of calcitonin gene-related peptide and markers of mast cell activation (tryptase and histamine) at fixed time points: at baseline (T0), at the end of the infusion (T20), 10 min after the infusion (T30), and 70 min after the infusion (T90). Results: Blood was collected from episodic cluster headache patients in active phase (n = 14), episodic cluster headache patients in remission (n = 15), and chronic cluster headache patients (n = 15). At baseline, plasma levels of calcitonin gene-related peptide, tryptase, and histamine were not different among the three study groups. Plasma levels of calcitonin gene-related peptide (p = 0.7074), tryptase (p = 0.6673), or histamine (p = 0.4792) remained unchanged during provoked attacks compared to attack-free patients. Conclusion: Cluster headache attacks provoked by either PACAP38 or vasoactive intestinal polypeptide were not accompanied by alterations of plasma calcitonin gene-related peptide, tryptase or histamine. The provoked attacks may not be mediated by calcitonin gene-related peptide or mast cell activation. Trial Registration : The study is registered at ClinicalTrials.gov (NCT03814226). [ABSTRACT FROM AUTHOR]

Introduction: The activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h infusion of VIP caused alterations in plasma levels of the calcitonin gene-related peptide (CGRP) and whether any changes might be related to the induced migraine attacks. Materials and Methods: We enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-h infusion of either VIP (8 pmol/kg/min) or placebo (sterile saline) in two randomized, placebo-controlled crossover trials. We collected clinical data and measured plasma levels of VIP and CGRP at fixed time points: at baseline (T0) and every 30 min until 180 min (T180) after the start of the infusion. Results: Blood samples were collected from patients with migraine (n = 19) and healthy individuals (n = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP (p = 0.027) at T30 (vs. T180, adjusted p- value = 0.039) and T60 (vs. T180, adjusted p -value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks (p = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP (p = 0.205) or placebo (p = 0.428) days. Discussion: Plasma CGRP was elevated in patients with migraine during a prolonged infusion of VIP, but these alterations were not associated with VIP-induced migraine attacks. Given the exploratory design of our study, further investigations are needed to clarify the role of CGRP in VIP-induced migraine. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03989817 and NCT04260035. [ABSTRACT FROM AUTHOR]

An editorial is presented on the role for pathways in improving quality treatment selection advancing into an era of precision medicine. Topics include focusing on the treatment of non–small-cell lung cancer (NSCLC) such as inappropriate drug utilization being a key contributor in rising drug costs; and using the combination of a platinum plus pemetrexed plus pembrolizumab.

Objective: To systematically identify risk factors for the development of post‐traumatic headache (PTH) attributed to traumatic brain injury (TBI) as defined in the International Classification of Headache Disorders (ICHD). Background: PTH is a common sequela of TBI and a leading cause of injury‐related disability worldwide. However, little is known about risk factors for the development of PTH attributed to TBI. Methods: We searched PubMed and Embase for literature on risk factors for the development of acute and/or persistent PTH attributed to TBI in accordance with any version of the ICHD. Original studies published in English and of prospective, cross‐sectional or retrospective design were considered for the review. Data extraction was performed independently by 2 investigators. Results: Of 1993 potentially relevant articles identified, 3 articles met the inclusion criteria. The following risk factors were assessed for the development of acute PTH: age, sex, type of injury, loss of consciousness, previous TBIs, history of primary headache disorders, history of chronic pain condition other than headache, current treatment for depression/anxiety, attention or learning disorders, body mass index, and other diseases (not further specified). None of the included studies assessed risk factors for the development of persistent PTH. Conclusions: We found that there is little evidence for any risk factors involved in the development of acute PTH, whereas no study had assessed risk factors for the development of persistent PTH. Further studies are warranted and should be powered to examine possible risk factors for the development of PTH. Rigorous methodology and standardized monitoring should be prioritized to support high‐quality research and validate potential findings. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to investigate whether levcromakalim, a KATP channel opener, induces migraine attacks in people with migraine pre-treated with erenumab, a monoclonal CGRP receptor antibody. Methods: In this double-blind, placebo-controlled, two-way cross-over study, adults with migraine without aura received a subcutaneous injection of 140 mg of erenumab on day 1. Subsequently, they were randomized to receive a 20-minute infusion of 0.05 mg/ml levcromakalim or placebo on two experimental days separated by at least one week (between days 8 and 21). The primary endpoint was the difference in the incidence of migraine attacks between levcromakalim and placebo during the 12-hour post-infusion period. Results: In total, 16 participants completed the study. During the 12-hour observation period, 14 (88%) of 16 participants experienced migraine attacks after levcromakalim, compared to two (12%) after placebo (p < 0.001). The area under the curve for median headache intensity was greater after levcromakalim than placebo (p < 0.001). Levcromakalim elicited dilation of the superficial temporal artery during the first hour after infusion, a response absent following placebo (p < 0.001). Conclusions: The induction of migraine attacks via opening of KATP channels appears independent of CGRP receptor activation. [ABSTRACT FROM AUTHOR]

The corrected funding statement are provided below: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by grants from Lundbeckfonden (grant R252-2017-1317) and Research Foundation of Rigshospitalet. In this article, the funding details were omitted in the initial OnlineFirst version. [Extracted from the article]

The article presents a discussion among mental health experts on the challenges that veterans face in receiving treatment for mental health conditions, chaired by Terence M. Keane. Jessica McNurlen stressed the need for awareness among private practitioners. Eileen Zeller said the U.S. Substance Abuse and Mental Health Services Administration faces discrimination against troops who seek services. John P. Docherty said practitioners should know the importance of educating the families.

Background: Previously reported increases in serum levels of vasodilating neuropeptides pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) during attacks of cluster headache could indicate their involvement in cluster headache attack initiation. We investigated the attack-inducing effects of PACAP38 and vasoactive intestinal peptide in cluster headache, hypothesising that PACAP38, but not vasoactive intestinal peptide, would induce cluster-like attacks in episodic active phase and chronic cluster headache patients. Methods: In a double-blind crossover study, 14 episodic cluster headache patients in active phase, 15 episodic cluster headache patients in remission phase and 15 chronic cluster headache patients were randomly allocated to receive intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal peptide (8 pmol/kg/min) over 20 min on two study days separated by at least 7 days. We recorded headache intensity, incidence of cluster-like attacks, cranial autonomic symptoms and vital signs using a questionnaire (0–90 min). Results: In episodic cluster headache active phase, PACAP38 induced cluster-like attacks in 6/14 patients and vasoactive intestinal peptide induced cluster-like attacks in 5/14 patients (p = 1.000). In chronic cluster headache, PACAP38 and vasoactive intestinal peptide both induced cluster-like attacks in 7/15 patients (p = 0.765). In episodic cluster headache remission phase, neither PACAP38 nor vasoactive intestinal peptide induced cluster-like attacks. Conclusions: Contrary to our hypothesis, attack induction was lower than expected and roughly equal by PACAP38 and vasoactive intestinal peptide in episodic active phase and chronic cluster headache patients, which contradicts the PAC1-receptor as being solely responsible for attack induction. Trial registration: clinicaltrials.gov (identifier NCT03814226). [ABSTRACT FROM AUTHOR]

Background: In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified.Methods: In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery diameter and headache intensity scores, as well as in headache incidence, between VIP and placebo.Results: The superficial temporal artery diameter was significantly larger on the VIP day compared to placebo (p < 0.001) and the dilation lasted for more than 2 h. The incidence of headache was higher (p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was more evident in the post-infusion period (120-200 min, p = 0.034) and in the post-hospital phase (4-12 h, p = 0.025). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo (p = 0.033).Conclusion: Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system, and delayed mild headaches in healthy volunteers.Trial Registration: The study is registered at ClinicalTrials.gov (NCT03989817). [ABSTRACT FROM AUTHOR]

Background: The present study investigates the wearing-off effect in adults with chronic migraine treated with erenumab or fremanezumab. Methods: This real-world observational study was based on pre-collected headache diaries from chronic migraine patients in treatment with either monthly injections of 140 mg of erenumab or 225 mg of fremanezumab. Consistent wearing-off was defined as an increase of ≥2 weekly migraine days in the last week compared to the second week over two consecutive 4-week treatment periods. The primary endpoint was wearing-off in the total population. The secondary endpoints were difference in wearing-off in (i) a subgroup of patients treated with erenumab and fremanezumab and (ii) consistent wearing-off in patients with a ≥30% reduction in monthly migraine days, compared to baseline, in the two consecutive treatment months. Results: In total, 100 patients (erenumab: n =60, fremanezumab: n =40) were included. Sixty-two out of 100 (62%) patients had consistent ≥30% treatment response on antibody therapy in both months (erenumab: n =36, fremanezumab: n =26). There was no consistent wearing-off over the two consecutive months from week 2 to week 4 (3.04%, p =0.558). There was no wearing-off within the erenumab (p =0.194) or the fremanezumab (p =0.581) groups. Among the ≥30% treatment responders, there was no consistent wearing-off over the two consecutive months (2.6%, p =0.573). Conclusions: There was no wearing-off in treatment responders, which is in alignment with premarketing data from placebo-controlled phase III studies. These data suggest that patients should be informed upfront that no wearing-off effect is expected because anxiety for attacks at the end of the month per se may generate migraine attacks. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether levcromakalim (a KATP channel opener) induces migraine-like headache in people with persistent post-traumatic headache who had no known history of migraine. Methods: In a randomized, double-blind, placebo-controlled, 2-way crossover trial, participants were randomly assigned to receive a 20-minute continuous intravenous infusion of levcromakalim (50 µg/mL) or placebo (isotonic saline) on two separate experimental days with a 1-week wash-out period in between. The primary endpoint was the difference in incidence of migraine-like headache between levcromakalim and placebo during a 12-hour observational period after infusion start. The secondary endpoint was the difference in area under the curve for baseline-corrected median headache intensity scores between levcromakalim and placebo during the 12-hour observational period. Results: A total of 21 participants with persistent post-traumatic headache were randomized and completed the trial. During the 12-hour observational period, 12 (57%) of 21 participants reported experiencing migraine-like headache following the levcromakalim infusion, compared with three after placebo (P = 0.013). Moreover, the baseline-corrected median headache intensity scores were higher following the levcromakalim infusion than after placebo (P = 0.003). Conclusion: Our findings suggest that KATP channels play an important role in the pathogenesis of migraine-like headache in people with persistent post-traumatic headache. This implies that KATP channel blockers might represent a promising avenue for drug development. Further research is warranted to explore the potential therapeutic benefits of KATP channel blockers in managing post-traumatic headache. Trial Registration : ClinicalTrials.gov Identifier: NCT05243953 [ABSTRACT FROM AUTHOR]

Objective: To assess the proportion of individuals who report dizziness and/or vertigo during the prodromal phase or headache phase of migraine.Methods: The databases of MEDLINE and EMBASE were searched for studies on dizziness and/or vertigo during the prodromal phase or headache phase of migraine. Pooled relative frequencies were estimated using a random-effects meta-analysis.Results: We identified nine articles eligible for inclusion. Of these, one study reported results for the prodromal phase, seven studies for the headache phase and one study for both the prodromal and headache phase. In the prodromal phase, 9.0% of individuals with migraine reported dizziness, while 3.3% reported vertigo. During the headache phase, relative frequency of dizziness ranged from 6.7% to 59.6%, while vertigo ranged from 6.4% to 44.7%. The meta-analysis showed a relative frequency of 35.7% for dizziness (95% CI = 13.7-61.5%, I2 = 99%) and 33.9% for vertigo (95% CI = 26.7-41.5%, I2 = 87%). Study quality was rated 5/9 or below for seven studies and 6/9 or above for two studies.Conclusion: We found that there is a scarcity of literature on dizziness and vertigo as prodromal- and headache-associated symptoms in individuals with migraine. Methodological variations confound comparisons of epidemiological patterns, although it appears that dizziness and vertigo are more frequent during the headache phase of migraine, compared with the prodromal phase. Future studies should ensure use of standardized definitions and rigorous methodology to enable accurate measurements of dizziness and vertigo in migraine. [ABSTRACT FROM AUTHOR]

Most cancer centers are ill-equipped to pursue value-based payment (VBP) because of limited information on their population's cost of care. Herein, we outline the stepwise approach used by Smilow Cancer Hospital at Yale-New Haven in our pursuit of better value care. First, we addressed institutional barriers. A move toward value required demonstration to Yale-New Haven Health System leadership that OCM would improve patient care, fund new infrastructure, and provide the opportunity to gain experience with VBP without a major threat to the financial stability of the health system. We evaluated patterns of care and found that of patients presenting to the emergency department (ED), 88% were admitted, 62% arrived during the workday, and 50% could have been stabilized with urgent care services. Within 30 days of death, 27% were admitted to the intensive care unit, 38% presented to the ED, and 52% were admitted. To quantify total cost of care, we accessed the 5% Medicare Limited Data Set to map out total cost of care for patients receiving chemotherapy at Smilow Cancer Hospital. Costs increased as patients moved through 6-month episodes, used the ED (patients with two or more visits were twice as expensive as those with one or fewer), or died during an episode (costs were twice as high as episodes in which the patient lived). To determine strategic interventions to improve value, we targeted investments in urgent care to reduce ED utilization, care management to prevent hospital admissions, and referral to palliative care for clarification of goals of care and avoidance of costly futile treatment. Developing internal metrics to evaluate success will require monitoring our interventions by having utilization measures for each site of care and individual provider. [ABSTRACT FROM AUTHOR]

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), known for its role in migraine pathogenesis, has been identified as a novel drug target. Given the clinical parallels between post-traumatic headache (PTH) and migraine, we explored the possible role of PACAP-38 in the pathogenesis of PTH. To this end, we conducted a randomized, double-blind, placebo-controlled, two-way crossover trial involving adult participants diagnosed with persistent PTH resulting from mild traumatic brain injury. Participants were randomly assigned to receive a 20-min continuous intravenous infusion of either PACAP-38 (10 pmol/kg/min) or placebo (isotonic saline) on two separate experimental days, with a 1-week washout period in between. The primary outcome was the difference in incidence of migraine-like headache between PACAP-38 and placebo during a 12-h observational period post-infusion. The secondary outcome was the difference in the area under the curve (AUC) for baseline-corrected median headache intensity scores during the same 12-h observational period. Of 49 individuals assessed for eligibility, 21 were enrolled and completed the trial. The participants had a mean age of 35.2 years, and 16 (76%) were female. Most [19 of 21 (90%)] had a migraine-like phenotype. During the 12-h observational period, 20 of 21 (95%) participants developed migraine-like headache after intravenous infusion of PACAP-38, compared with two (10%) participants after placebo (P < 0.001). Furthermore, the baseline-corrected AUC values for median headache intensity scores during the 12-h observational period was higher after PACAP-38 than placebo (P < 0.001). These compelling results demonstrate that PACAP-38 is potent inducer of migraine-like headache in people with persistent PTH. Thus, targeting PACAP-38 signalling might be a promising avenue for the treatment of PTH., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)