Whether Weather Matters with Migraine.

PURPOSE OF REVIEW: Many patients with migraine report their attacks are triggered by various weather anomalies. Studies have shown mixed results regarding the association of migraine to weather changes. The purpose of the current review is to compile the most up-to-date research studies on how weather may affect migraine. In addition, we explore the association between weather and other inflammatory disease states as well as neurotransmitters. RECENT FINDINGS: Migraine attacks can be related to weather variables such as barometric pressure, humidity, and wind. However, the results of recent studies are inconsistent; weathers' effect on migraine attacks is around 20%. However, very strong weather factors have a more significant effect on migraine attack variables. Many individuals identify weather as a migraine attack trigger, yet we see no causative relationship between weather and migraine patterns. The outcomes of studies indicate mixed results and reflect individual variation in how weather can impact migraine patterns. Similar relationships can be seen with other rheumatologic and pain conditions in general. Overall, the combination of weather plus other factors appears to be a more significant migraine trigger.

Inducible plasmid copy number control for synthetic biology in commonly used E. coli strains.

The ability to externally control gene expression has been paradigm shifting for all areas of biological research, especially for synthetic biology. Such control typically occurs at the transcriptional and translational level, while technologies enabling control at the DNA copy level are limited by either (i) relying on a handful of plasmids with fixed and arbitrary copy numbers; or (ii) require multiple plasmids for replication control; or (iii) are restricted to specialized strains. To overcome these limitations, we present TULIP (TUnable Ligand Inducible Plasmid): a self-contained plasmid with inducible copy number control, designed for portability across various Escherichia coli strains commonly used for cloning, protein expression, and metabolic engineering. Using TULIP, we demonstrate through multiple application examples that flexible plasmid copy number control accelerates the design and optimization of gene circuits, enables efficient probing of metabolic burden, and facilitates the prototyping and recycling of modules in different genetic contexts.

Reductions in acute medication use and healthcare resource utilization in patients with chronic migraine: a secondary analysis of a phase 3, randomized, double-blind, placebo-controlled study of galcanezumab with open-label extension (REGAIN).

AIMS: To analyze secondary objectives of the REGAIN study related to acute headache medication use and healthcare resource utilization (HCRU) in patients with chronic migraine treated with galcanezumab, a monoclonal antibody to calcitonin gene-related peptide. METHODS: Adults with chronic migraine (N = 1,113) were randomized (2:1:1) and treated with double-blind monthly injections of placebo, galcanezumab-120 mg, or galcanenzumab-240 mg for 3 months, followed by a 9-month open-label extension with 120 or 240 mg/month galcanezumab. Headache and medication information was collected by daily eDiary. HCRU was reported for the 6 months before randomization, monthly thereafter, and converted to rate per 100-patient-years. RESULTS: At baseline, 63-64% of patients met criteria for acute headache medication overuse. At Month 3, incidence of headache medication overuse in the galcanezumab groups (33% and 33%) was significantly lower than in the placebo group (46%, both p < .001) and was 16% and 23% in the previous-galcanezumab groups at Month 12. From a baseline of 14.5 to 15.5, reduction in mean number of monthly migraine headache days with acute headache medication use was also significantly greater in the galcanezumab groups at Month 3 (-4.2 and -4.9) than in placebo (-2.6, both p < .001), with reductions of -6.8 and -7.6 in the previous-galcanezumab groups at Month 12. Migraine-specific HCRU rates decreased for all groups, with no significant between-group differences at Month 3. At Month 12, in the two previous-galcanezumab groups, emergency room visits decreased by 58% and 75%, hospital admissions by 100%, and healthcare professional visits by 54% and 67%. LIMITATIONS: Only 3 months of double-blind, placebo-controlled data, a longer HCRU recall period for baseline than postbaseline, and patients receiving care in the clinical trial itself, may limit generalizability. CONCLUSIONS: Treatment with galcanezumab resulted in significant reductions in headache medication overuse and migraine headache days requiring acute medication use, with notable reductions in migraine-specific HCRU.

A narrative review of the importance of pharmacokinetics and drug-drug interactions of preventive therapies in migraine management.

OBJECTIVE: To review the pharmacokinetics of major classes of migraine preventives and the clinical implications of drug-drug interactions (DDIs) with the use of these therapies in migraine management. BACKGROUND: Preventive treatments for migraine are recommended for a large proportion of patients with frequent migraine attacks. These patients often exhibit a number of comorbidities, which may lead to the introduction of multiple concomitant therapies. Potential DDIs must be considered when using polytherapy to avoid increased risk of adverse events (AEs) or inadequate treatment of comorbid conditions. METHODS: A literature search was performed to identify pharmacokinetic properties and potential DDIs of beta-blockers, antiepileptic drugs, antidepressants, calcium channel blockers, gepants, and monoclonal antibody therapies targeting the calcitonin gene-related peptide pathway with medications that may be used for comorbid conditions. RESULTS: Most DDIs occur through alterations in cytochrome P450 isoenzyme activity and may be complicated by genetic polymorphism for metabolic enzymes. Additionally, drug metabolism may be altered by grapefruit juice ingestion and smoking. The use of migraine preventive therapies may exacerbate symptoms of comorbid conditions or increase the risk of AEs associated with comorbid conditions as a result of DDIs. CONCLUSIONS: DDIs are important to consider in patients with migraine who use multiple medications. The development of migraine-specific evidence-based preventive treatments allows for tailored clinical management that reduces the risk of DDIs and associated AEs in patients with comorbidities.

Real-World Treatment Profiles, Clinical Outcomes, and Healthcare Resource Utilization of Patients with Migraine Prescribed Erenumab: A Multicenter Chart-Review Study of US Headache Centers.

INTRODUCTION: Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults. There is limited data available on its impact in real-world settings. The study aim was to characterize the real-world treatment profiles, clinical outcomes, and healthcare resource utilization of patients prescribed erenumab from select major US headache centers. METHODS: A retrospective chart review of patients with migraine treated with erenumab for at least 3 months across five major headache centers was conducted. Data was collected from patient charts between April 2019 and April 2020 and included patient and clinical characteristics, migraine medication use, and outpatient visits. The date of the first prescription fill of erenumab was defined as the index date. The baseline period comprised the 3 months prior to the index date and the study period comprised the at least 3 months on erenumab treatment. RESULTS: Data from a total of 1034 patients with chronic migraine with a mean of 9.3 months of erenumab treatment were analyzed. Patients were on average 48 years old, 86% were female, and 79% were white. Patients had a mean of 5 preventive treatment failures prior to erenumab initiation. Patients used a mean of 2 preventive treatments (excluding erenumab) and 2 acute treatments during baseline and study periods. Among patients with effectiveness data, 45% of patients had improvement in physician-reported migraine severity and 35% experienced at least 50% reduction in mean headache/migraine days per month. The average number of monthly outpatient visits was 0.43 and 0.30 before and after erenumab initiation, respectively. CONCLUSION: In this predominantly refractory chronic migraine population treated in select headache centers, patients had fewer headache/migraine days per month and outpatient visits after initiating erenumab. However, patients largely continued to be managed via a polypharmacy approach after erenumab initiation.

Economic burden and risk factors of migraine disease progression in the US: a retrospective analysis of a commercial payer database.

AIMS: To evaluate the prevalence and risk factors of migraine progression and to assess the incremental burden of migraine progression on healthcare systems. MATERIALS AND METHODS: Adult patients were required to have a migraine diagnosis in IQVIA's US adjudicated claims database between 1 January 2012 and 30 June 2016, continuous enrollment ≥12 months before and after the index date (i.e. the first observed migraine diagnosis), and ≥1 additional migraine diagnosis claim during the 12-month post-index period. A previously-developed algorithm identified patients with prevention-eligible episodic migraine (EM). All-cause healthcare resource utilization (HCRU) and costs were evaluated at baseline, over the follow-up period and pre/post progression from prevention-eligible EM to chronic migraine. Cox proportional hazards models were used to evaluate risk factors associated with progression. RESULTS, LIMITATIONS, AND CONCLUSIONS: Of the 125,436 patients with prevention-eligible EM that were initially identified, 5,790 (4.6%) were further identified as progressed. Patients who progressed had higher healthcare costs and higher medication use at baseline compared to patients that did not progress. Mean (SD) all-cause total costs per patient per month were $1,790 ($3,788), significantly higher in the post-progression period compared to $1,414 ($2,456) in the pre-progression period in patients who progressed (p < .0001). Younger age, female sex, initial diagnosis by a neurologist, chronic pain, and use of triptans and/or non-specific acute medications were all significant progression risk factors. Results are limited by the use of a heterogeneous population (incident, prevalent, treated, and untreated patients), coding biases, and lack of information on non-prescription drug utilization and plan limits. Limitations aside, there are substantial HCRU and cost burden associated with migraine progression. Younger age, female sex, and the use of specific drug classes are likely to increase migraine disease progression risk.

A Real-World Analysis of Patient Characteristics, Treatment Patterns, and Level of Impairment in Patients With Migraine Who are Insufficient Responders vs Responders to Acute Treatment.

OBJECTIVE: The objective of this study was to examine if patients with migraine who responded sufficiently to acute treatment were significantly different from those who did not in terms of patient characteristics, treatment patterns, and patient level of impairment, and to identify characteristics associated with insufficient response. BACKGROUND: Migraine is highly prevalent and impacts functional ability substantially. Current treatment approaches are not sufficiently meeting the needs of patients, and inadequate response to acute treatment is reported by at least 56% of patients with migraine in the United States. METHODS: Data were obtained from the 2014 Adelphi Migraine Disease-Specific Program, a cross-sectional survey. Using logistic regression, we assessed the association between patient factors and insufficient response. Responders were defined as patients with migraine who achieved pain freedom within 2 hours of acute treatment in ≥4 of 5 attacks, while insufficient responders achieved it in ≤3 of 5 attacks. RESULTS: Of 583 patients included, insufficient responders to acute treatment constituted 34.3% (200/583) of the study population. A statistically significantly larger proportion of insufficient responders vs responders had ≥4 migraine headache days/month (46.3% [88/190] vs 31% [114/368]), had ever been prescribed ≥3 unique preventive treatment regimens (11.7% [21/179] vs 6.3% [22/347]), and had chronic migraine, medication-overuse headaches, and comorbid depression (all P values ≤.05). Patient level of impairment was statistically significantly greater among insufficient responders vs responders. Factors associated with insufficient response after adjusting for covariates included Migraine Disability Assessment total score (odds ratio [OR] = 1.04, 95% CI [1.02, 1.05]), time of administration of acute treatment (OR = 1.83, 95% CI [1.15, 2.92]), depression (OR = 1.98, 95% CI [1.21, 3.23]), sensitivity to light not listed as current most troublesome symptom (OR = 2.30, 95% CI [1.21, 4.37]), and change in the average headache days per month before being prescribed an acute treatment vs now (OR = 1.75, 95% CI [1.05, 2.90]). CONCLUSIONS: Clinical characteristics, treatment patterns, and health-related quality of life measures are statistically significantly different between insufficient responders and responders to acute treatment in patients with migraine.

A global real-world assessment of the impact on health-related quality of life and work productivity of migraine in patients with insufficient versus good response to triptan medication.

BACKGROUND: Migraine is a chronic, disabling neurological disease characterized by moderate-to-severe headache pain with other symptoms, including nausea, vomiting, and photophobia. Triptans, while generally effective, are insufficiently efficacious in 30-40% of patients and poorly tolerated by or contraindicated in others. We assessed the impact of insufficient response to triptans on health-related quality of life (HRQoL) and work productivity in patients currently receiving any prescribed triptan formulation as their only acute migraine medication. METHODS: Data were from the 2017 Adelphi Migraine Disease Specific Programme, a cross-sectional survey of primary care physicians, neurologists, and headache specialists and their consulting patients with migraine in the USA, France, Germany, Italy, Spain, and UK. Triptan insufficient responders (TIRs) achieved freedom from headache pain within 2 h of acute treatment in ≤3/5 migraine attacks; triptan responders (TRs) achieved pain freedom within 2 h in ≥4/5 attacks. Multivariable general linear model examined differences between TIRs and TRs in HRQoL and work productivity. Logistic regression identified factors associated with insufficient response to triptans. RESULTS: The study included 1413 triptan-treated patients (TIRs: n = 483, 34.2%; TRs: n = 930, 65.8%). TIRs were more likely to be female (76% vs. 70% for TIRs vs TRs, respectively; p = 0.011), older (mean age 42.6 vs. 40.5 years; p = 0.003), and had more headache days/month (7.0 vs. 4.4; p < 0.001). TIRs had significantly more disability, with higher Migraine Disability Scores (MIDAS; 13.2 vs. 7.7; p < 0.001), lower Migraine-specific Quality of Life scores, indicating greater impact (Role Function Restrictive: 62.4 vs. 74.5; Role Function Preventive: 70.0 vs. 82.2; Emotional Function: 67.7 vs. 82.1; all p < 0.001), and lower EQ5D utility scores (0.84 vs. 0.91; p = 0.001). Work productivity and activity were impaired (absenteeism, 8.6% vs. 5.1% for TIRs vs. TRs; presenteeism, 34.3% vs. 21.0%; work impairment, 37.1% vs. 23.3%; overall activity impairment, 39.8% vs. 25.3%; all p < 0.05). CONCLUSION: HRQoL and work productivity were significantly impacted in TIRs versus TRs in this real-world analysis of patients with migraine acutely treated with triptans, highlighting the need for more effective treatments for patients with an insufficient triptan response. Further research is needed to establish causal relationships between insufficient response and these outcomes.

Peptides, MAbs, Molecules, Mechanisms, and More: Taking a Stab at Cluster Headache.

BACKGROUND: Cluster headache is a highly disabling neurological disorder. PURPOSE: The purpose of this review is to highlight recent therapeutic advances in the treatment of cluster headache such as monoclonal antibodies as well as non-invasive vagus nerve stimulation, and examine future potential therapeutic targets. DISCUSSION: Several therapeutic agents currently in use may have underlying mechanisms important to cluster headache pathophysiology and have yet to be completely elucidated. The psychobiological aspects of cluster headache have a significant impact on patients, as well as pose limitations for treatment. Neuropeptides may play a role in underlying mechanisms in why cluster headache patients are frequent tobacco smokers. Alterations in the hypothalamic-pituitary-adrenal axis and neuroinflammation may play a role in suicidality. The circadian nature of cluster headache may generate the development of future treatment options. New understanding of mechanisms underlying post-traumatic headache may also provide insights into cluster headache pathophysiology. CONCLUSION: Molecular targets and neuromodulation advances have paved the way for a new generation of therapeutic agents in cluster headache. There are several other potential targets.

Predicting initiation of preventive migraine medications: exploratory study in a large U.S. medical claims database.

Objective: Despite guidelines that identify potential patients eligible for preventive migraine medications, their underutilization leaves patients at risk of acute medication overuse, disease progression, and higher healthcare resource utilization and disability. This exploratory, retrospective, observational study aimed to identify which factors predict preventive migraine medication initiation. Demographics and initiation of acute medication use were hypothesized to be predictive of initiation of preventive migraine medication.Methods: The Truven Health Analytics MarketScan1 U.S. Commercial and Medicare Supplemental claims database (2011-2013) was used to identify adults newly diagnosed with migraine. Patients were divided into 2 subgroups: initiated a preventive migraine medication (antidepressants, anti-epileptics, beta-blockers, or neurotoxins) within 1 year of migraine diagnosis and did not initiate a preventive migraine medication. Logistic regression models were constructed to identify factors associated with preventive migraine medication initiation.Results: Study population included 147,923 patients: 43,660 preventive migraine medication initiators and 104,263 non-preventive migraine medication patients. Best-fit model for predicting preventive migraine medication initiation included: female gender (odds ratio = 1.181 [95% CI = 1.144,1.218]; measured at date of first migraine diagnosis); headache diagnosis prior to migraine diagnosis (odds ratio = 1.538 [95% CI = 1.498,1.579]; measured 1-year before first migraine diagnosis); and sleep disorder (odds ratio = 1.206 [95% CI = 1.161,1.252]), headache/migraine-specific Emergency Department (ED) visit (odds ratio = 1.224 [95% CI = 1.168,1.283]), neurologist visit (odds ratio = 1.502 [95% CI = 1.459,1.547]), and acute medication refills with <90-day gap (odds ratio = 1.509 [95% CI = 1.470,1.549]) each measured at 1-year before first preventive migraine medication.Conclusions: In addition to consistent acute medication refills, specific comorbidity diagnoses, headache/migraine-specific ED utilization, and neurologist care are predictive of preventive migraine medication initiation in the 1-year post-incident migraine diagnosis.

Sherpas, Coca Leaves, and Planes: High Altitude and Airplane Headache Review with a Case of Post-LASIK Myopic Shift.

PURPOSE OF REVIEW: High altitude headache is a common neurological symptom that is associated with ascent to high altitude. It is classified by the International Classification of Headache Disorders, 3rd Edition (ICHD-3) as a disorder of homeostasis. In this article, we review recent clinical and insights into the pathophysiological mechanisms of high altitude and airplane headache. We also report a second case of post-LASIK myopic shift at high altitude exposure secondary hypoxia. Headache attributed to airplane travel is a severe typically unilateral orbital headache that usually improves after landing. This was a relative recent introduction to the ICHD-3 diagnostic criteria. Headache pain with flight travel has long been known and may have been previously considered as a part of barotrauma. Recent studies have helped identify this as a distinct headache disorder. RECENT FINDINGS: Physiologic, hematological, and biochemical biomarkers have been identified in recent high altitude studies. There have been recent advance in identification of molecular mechanisms underlying neurophysiologic changes secondary to hypoxia. Calcitonin gene-related peptide, a potent vasodilator, has been implicated in migraine pathophysiology. Recent epidemiological studies indicate that the prevalence of airplane headache may be more common than we think in the adult as well at the pediatric population. Simulated flight studies have identified potential biomarkers. Although research is limited, there have been advances in both clinical and pathophysiological mechanisms associated with high altitude and airplane headache.

The comorbidity burden of patients with cluster headache: a population-based study.

BACKGROUND: Evidence is limited regarding the comorbidity burden of patients with cluster headache (CH). We aimed to characterize comorbid conditions in a cohort of CH patients diagnosed by headache experts, using electronic health record information from the Partners Research Patient Data Registry (RPDR). METHODS: We identified and reviewed the charts of unique patients diagnosed by headache specialists over an 11-year period, and a set of matched controls. Patients were categorized as having Definite, Unconfirmed or no CH. We calculated the prevalence of and tested for statistically significant differences of selected comorbid conditions in these populations. RESULTS: An RPDR query identified 170 patients with a free text or ICD diagnosis of cluster headache. 15 records belonging to Partners employees were excluded. 75 patients met diagnostic criteria for CH (Definite CH). 22 had headaches with some features of CH but the diagnosis was uncertain (Unconfirmed CH). In 58 the diagnosis was determined to be inaccurate due to data entry errors. Patients with Definite CH had an average age of 43.4 years; 80% were male. The average time from CH onset to diagnosis was 12.7 years (range 1-51). The average number of yearly emergency department and outpatient visits for the group of Definite CH patients was 4.5 and 25.4, respectively, compared with 1.1 and 6.9 in controls. Of the 55 examined conditions, four were statistically significantly less common in patients with definite CH compared with controls (diabetes, musculoskeletal/orthopaedic problems, "other gastrointestinal diagnoses" and skin conditions) and four were statistically significantly more common (smoking, depression, dental disorders and deviated septum). CONCLUSIONS: In this large population-based study, we identified a surprisingly small number of patients who met strict diagnostic criteria for CH. In these patients, however, we identified a distinct pattern of selected comorbidities. The pattern is somewhat but not entirely consistent with that of the "classic" CH patient depicted in the medical literature. CH patients are frequently diagnosed with sinus or dental problems. Many experience substantial delay in receiving a diagnosis. These things may in part explain the high frequency of medical visits in this population. It is difficult to distinguish conditions that are genuinely comorbid with CH from those that reflect misdiagnoses or medical scrutiny of patients in frequent contact with the healthcare system.

Clinical Characteristics and Treatment Patterns Among Patients Diagnosed With Cluster Headache in U.S. Healthcare Claims Data.

OBJECTIVE: To characterize demographics, clinical characteristics, and treatment patterns of patients with cluster headache (CH). BACKGROUND: CH is an uncommon trigeminal autonomic cephalalgia with limited evidence-based treatment options. Patients suffer from extremely painful unilateral headache attacks and autonomic symptoms with episodic and chronic cycles. DESIGN/METHODS: This retrospective analysis used insurance claims from Truven Health Analytics MarketScan® research databases from 2009 to 2014. Two cohorts were compared: CH patients (with ≥2 CH claims) were propensity score matched with 4 non-headache controls, all with continuous enrollment for 12 months before and after the date of first CH claim or matched period among controls. RESULTS: CH patients (N = 7589) were mainly male (57.4%) and 35-64 years old (73.2%), with significantly more claims for comorbid conditions vs controls (N = 30,341), including depressive disorders (19.8% vs 10.0%), sleep disturbances (19.7% vs 9.1%), anxiety disorders (19.2% vs 8.7%), and tobacco use disorders (12.8% vs 5.3%), with 2.5 times greater odds of suicidal ideation (all P < .0001). Odds of drug dependence were 3-fold greater among CH patients (OR = 2.8 [95% CI 2.3-3.4, P < .0001]). CH patients reported significantly greater use of prescription medications compared with controls; 25% of CH patients had >12 unique prescription drug claims. Most commonly prescribed drug classes for CH patients included: opiate agonists (41%), corticosteroids (34%), 5HT-1 agonists (32%), antidepressants (31%), NSAIDs (29%), anticonvulsants (28%), calcium antagonists (27%), and benzodiazepines (22%). Only 30.4% of CH patients received recognized CH treatments without opioids during the 12-month post-index period. These patients were less likely to visit emergency departments or need hospitalizations (26.8%) as compared to CH patients with no pharmacy claims for recognized CH treatments or opioids (33.6%; P < .0001). CONCLUSIONS: The burden of CH is associated with significant co-morbidity, including substance use disorders and suicidal ideation, and treatment patterns indicating low use of recognized CH treatments.

Diclofenac potassium for oral solution (CAMBIA®) in the acute management of a migraine attack: clinical evidence and practical experience.

Migraine headache affects about 12% of Western populations and is the third most common disease worldwide (sixth in terms of disability). In 1993, triptans were introduced in the United States as a new treatment for managing migraine attacks, but their use is limited by lack of response and safety concerns in some patients. Treatment options for patients with migraine who fail or cannot tolerate triptans include switching to another medication or adding an adjunctive medication. Desirable characteristics reported by patients for acute treatment of migraine attacks include complete pain relief, fast onset of action, and no pain recurrence. Diclofenac is a nonsteroidal anti-inflammatory medication that has been established as effective for acute treatment of migraine by the American Headache Society based on available evidence. Diclofenac potassium for oral solution is rapidly absorbed, achieving maximal plasma concentrations in 15 min, which coincides with a rapid onset of effect. In a comparison of diclofenac potassium for oral solution with diclofenac potassium tablets, the solution achieved a significant reduction in headache intensity beginning at 15 min compared with 60 min for the tablet. Across randomized clinical trials, approximately 25% of patients were pain free 2 h after administration of diclofenac oral solution and the effects were maintained over a 24-h period. Diclofenac potassium for oral solution is well tolerated; the most common adverse events are dizziness and gastrointestinal complaints, with incidences similar to placebo. No serious adverse events have been reported in clinical trials of diclofenac potassium for oral solution in the acute treatment of migraine. Diclofenac oral solution may offer rapid and sustained pain relief for patients who do not achieve pain resolution with other medications. In addition, patients who experience central sensitization with allodynia may benefit from the cyclooxygenase-blocking activity of diclofenac, which is needed in this advanced phase of migraine.

Validity of cluster headache diagnoses in an electronic health record data repository.

BACKGROUND: Cluster headache (CH) is uncommon, so electronic searches of large medical record databases provide an important opportunity to identify a sufficient number of patients for research, patient registries, or quality improvement work. However, the accuracy of CH diagnoses recorded in electronic health record (EHR) databases is unknown. The Research Patient Data Registry (RPDR) warehouses information from EHR of two academic medical centers in Boston. We assessed the validity of CH diagnoses in the RPDR as well as the sensitivity of International Classification of Headache Disorders (ICHD) diagnostic criteria in relation to the gold standard of expert clinician diagnosis of CH. METHODS: In 2013, we queried RPDR to identify all patients diagnosed with CH diagnosed by headache specialists from 2002 to 2012. We sought to determine the positive predictive value (PPV) of an EHR diagnosis of CH relative to a headache expert's clinical impression as the gold standard. We also calculated the sensitivity of ICHD-2 CH criteria compared with the gold standard of expert-diagnosed CH cases. RESULTS: RPDR queries identified 170 patients with a diagnosis of CH. Two researchers carried out a detailed chart review searching for information to support or refute this diagnosis. In 58 cases, the diagnosis of CH was determined to be inaccurate due to data entry errors. The PPV of an RPDR diagnosis of CH was 63% (95% CI 54-71%) and the sensitivity of ICHD-2 criteria compared with the gold standard of expert diagnosis was 77% (95% CI 69-82%). CONCLUSIONS: The PPV of EHR diagnoses of CH is modest. Data entry errors are common, and only about three-fourths of CH cases diagnosed by expert clinicians meet ICHD criteria for CH. Thus, EHR searches for patients with CH frequently will result in false positives. This has implications for activities such as research, quality improvement efforts, or disease registries that rely on EHR searches to identify patients. Further work is needed to develop high quality phenotypic algorithms so that the research potential of EHRs can be realized.

A retrospective analysis of triptan and dhe use for basilar and hemiplegic migraine.

BACKGROUND: Patients with basilar migraine (BM) and hemiplegic migraine (HM) have been excluded from triptan and DHE clinical trials due to a potential risk of ischemic vascular events, and the FDA mandates that package labeling state that they are contraindicated in BM and HM. The objective of this study was to demonstrate that triptans and DHE can be used for the abortive treatment of BM and HM without significant adverse ischemic vascular events. METHODS: A retrospective chart review of patients with BM features or HM who received acute abortive treatment with either triptans or DHE was conducted at 4 headache centers to assess the frequency of ischemic vascular events after administration. The diagnoses of BM or HM were made by headache specialists based on The International Classification of Headache Disorders, 2nd edition (ICHD-II). Searchable terms included BM, vertigo, dysarthria, diplopia, hemiplegia/hemiparesis, facial droop, weakness, confusion, altered consciousness, confusion, ataxia, and aphasia, as well as all triptans or DHE. RESULTS: The study included 67 patients with BM features and 13 patients with HM. Among those receiving triptans, 40 were in the BM group and 5 were in the HM group. Among those receiving DHE, 27 were included in the BM group and 8 were in the HM group. No side effects of stroke or myocardial infarction were reported. In the triptan group, 5 patients reported adverse effects that included GI upset, rash, neck dystonia, nightmares, and flushing. In the DHE group, 5 patients had adverse events that included chest tightness, dystonic reaction, transient asymptomatic anterior T wave inversion, and agitation. CONCLUSION: In this retrospective study, triptans and DHE were used with no reported, subsequent acute/subacute ischemic vascular events for the abortive treatment of migraines with basilar and hemiplegic-type features. Although the small sample sizes generated theoretical statistical event rates of 4.5% for BM and 23% for HM, there has been no clear evidence that BM and HM carry an actual elevated risk for vascular events compared with migraine with aura.

Pathophysiological mechanisms of headache in patients with HIV.

BACKGROUND: The pathophysiology of human immunodeficiency virus (HIV) is complex. The etiology of headache in the HIV population is often multifactorial, and attributing causality to specific pathophysiological mechanisms is challenging. Headaches can occur any time during the infection and may be primary (as in non-HIV-infected patients) or secondary (either from HIV directly or due to opportunistic disease). DISCUSSION: Direct HIV related headaches are due to the underlying viral pathophysiology. For example, acute meningitis can be seen during HIV-1 seroconversion. Headaches can occur during symptomatic HIV and also after an AIDS-defining illness. Late-stage HIV headache can occur without any pleocytosis. A correlation between viral load and neurological symptoms including headache has been suggested. There may be similar mechanisms involving migraine, tension-type headache, and HIV infection. CONCLUSION: Secondary HIV headaches can be related to opportunistic infections, malignancy, medications used to treat HIV, and immune restoration inflammatory syndrome.

New daily persistent headache and potential new therapeutic agents.

New daily persistent headache is a form of a chronic daily headache with a unique temporal profile. Patients can recall the exact day when their headache started. It can be one of the most refractory types of headache to treat. Recent publications have highlighted different subtypes and heterogeneity in presentation. Referring to it as a syndrome versus a distinct disorder has also been suggested. Several different classes of medications have been used for the treatment, with mixed results. The underlying pathophysiology of new daily persistent headache is unclear, but tumor necrosis factor may play a role. The clinical features, differential diagnosis and potential new therapeutic agents will be discussed.

Anthrax in America 2001-2003.

Anthrax caused by Bacillus anthracis in humans is rare. Two recent outbreaks that were intentionally caused occurred among postal employees, politicians, and journalists in the United States. This has caused tremendous fear, and our experience with these "anthrax incidents" has changed our views on the natural history of this disease in people. In this paper, we review the lifecycle and biology of this micro-organism. Anthrax that occurs from a weaponized form of this micro-organism has a specific clinical presentation that requires a suspicion of anthrax exposure to be diagnosed. New methods of testing for anthrax have been developed and may simplify diagnosis in the future. The range of illness caused by B. anthracis from the molecular level to the clinical symptoms is discussed. We also review the diagnostic criteria and differential diagnosis as well as treatment of this condition.