Serotonin syndrome in the acute treatment landscape of migraine: the lasmiditan experience.

Background: Serotonin syndrome (SS) symptoms overlap with adverse events associated with lasmiditan, a 5-HT (serotonin)1F receptor agonist for acute treatment of migraine. Because SS symptoms are heterogeneous, diagnosis can be challenging, and potential cases observed with lasmiditan treatment led to questions about SS pathophysiology. Here, we provide an overview of the potential risk of SS based on experience with lasmiditan. Methods: Results of eight phase 2 and phase 3 lasmiditan trials (n = 5,916) and a controlled intravenous trial of lasmiditan (n = 88) were analyzed for symptomatology consistent with SS. Post-marketing surveillance data from lasmiditan's US launch date (January 2020) until data cut-off (April 2021) were also examined. Established Sternbach and Hunter diagnostic criteria were used for formal determination of SS. Results: Of 6,004 lasmiditan-treated clinical trial patients, 15 reported ≥1 treatment-emergent adverse event consistent with signs and symptom(s) of SS. After review, one case met Sternbach and Hunter criteria, two cases potentially met Sternbach criteria, and three cases reported as SS had limited/no information to determine if either criterion was met. During post-marketing surveillance (approximately 13,400 lasmiditan prescriptions), 17 cases with symptom complexes consistent with SS were reported; 3/17 cases had adequate case descriptions to apply predefined criteria. Of these, two met Sternbach and Hunter criteria, and one met Sternbach criteria. Conclusion: Awareness of clinical symptomatology and diagnostic criteria of SS can help clinicians with recognition of rare instances of SS that may occur with lasmiditan. Clinical trial registration: NCT03670810, NCT00384774, NCT00883051, NCT02565186.

Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine.

OBJECTIVE: To evaluate, at population and individual patient levels, the sustained response of reduction in migraine headache days in patients with migraine treated with galcanezumab. METHODS: This was a post hoc analysis of double-blind galcanezumab studies in patients with migraine: two 6-month episodic migraine (EM; EVOLVE-1/EVOLVE-2), one 3-month chronic migraine (CM; REGAIN), and one 3-month treatment-resistant migraine (CONQUER). Patients received monthly subcutaneous galcanezumab 120 mg (after 240 mg initial loading dose), galcanezumab 240 mg, or placebo. In the EM and CM studies, the proportions of patients with ≥50% and ≥75% (EM only) reduction from baseline in average monthly migraine headache days from Months 1 to 3 and Months 4 to 6 were evaluated. A mean monthly response rate was estimated. The sustained effect was defined as maintaining ≥50% response for ≥3 consecutive months in the patient-level data for EM and CM. RESULTS: A total of 3348 patients with EM or CM from the EVOLVE-1/EVOLVE-2 (placebo, n = 894, galcanezumab, n = 879), REGAIN (placebo, n = 558, galcanezumab, n = 555), and CONQUER (EM: placebo, n = 132, galcanezumab, n = 137; CM: placebo, n = 98, galcanezumab, n = 95) studies were included. Patients were predominantly female, White, and had monthly migraine headache day averages ranging from 9.1 to 9.5 days (EM) and 18.1 to 19.6 days (CM). In patients with EM and CM, 19.0% and 22.6% of galcanezumab-treated patients, respectively, had significantly higher maintenance of ≥50% response for all months in the double-blind period compared to 8.0% and 1.5% of placebo-treated patients. The odds ratios (OR) of achieving clinical response for EM and CM were double with galcanezumab (OR = 3.0 [95% CI 1.8, 4.8] and OR = 6.3 [95% CI 1.7, 22.7], respectively). At the individual patient level, of patients who had ≥75% response at Month 3 in the galcanezumab 120 and 240 mg dose groups and placebo group, 39.9% (55/138) and 43.0% (61/142), respectively, of galcanezumab-treated patients maintained ≥75% response during Months 4-6 compared to 32.7% (51/156) with placebo. CONCLUSION: More galcanezumab-treated patients achieved ≥50% response within the first 3 months of treatment compared to placebo; responses were sustained during Months 4-6. The odds of achieving ≥50% response were double with galcanezumab.

The not so hidden impact of interictal burden in migraine: A narrative review.

Migraine is a highly prevalent neurological disease of varying attack frequency. Headache attacks that are accompanied by a combination of impact on daily activities, photophobia and/or nausea are most commonly migraine. The headache phase of a migraine attack has attracted more research, assessment tools and treatment goals than any other feature, characteristic, or phase of migraine. However, the migraine attack may encompass up to 4 phases: the prodrome, aura, headache phase and postdrome. There is growing recognition that the burden of migraine, including symptoms associated with the headache phase of the attack, may persist between migraine attacks, sometimes referred to as the "interictal phase." These include allodynia, hypersensitivity, photophobia, phonophobia, osmophobia, visual/vestibular disturbances and motion sickness. Subtle interictal clinical manifestations and a patient's trepidation to make plans or commitments due to the unpredictability of migraine attacks may contribute to poorer quality of life. However, there are only a few tools available to assess the interictal burden. Herein, we examine the recent advances in the recognition, description, and assessment of the interictal burden of migraine. We also highlight the value in patients feeling comfortable discussing the symptoms and overall burden of migraine when discussing migraine treatment needs with their provider.

Efficacy of lasmiditan for the acute treatment of perimenstrual migraine.

BACKGROUND: Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT1F receptor agonist, for perimenstrual attacks. METHODS: Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated. RESULTS: A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p < 0.001), and 16.7% of patients in the 100-mg (p = 0.11) and 50-mg (p = 0.19) groups were pain free, compared with 7.6% in the placebo group. CONCLUSIONS: Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy.Clinical Trial registration: NCT03962738 and NCT03670810.

Potential Channeling Bias in the Evaluation of Cardiovascular Risk: The Importance of Comparator Selection in Observational Research.

BACKGROUND: Comparator selection is an important consideration in the design of observational research studies that evaluate potential associations between drug therapies and adverse event risks. It can affect the validity of observational study results, and potentially impact data interpretation, regulatory decision making, and patient medication access. OBJECTIVE: The aim of this study was to assess the impact of comparator selection bias using two real-world case studies evaluating an increased rate of acute myocardial infarction (AMI). METHODS: Data from the Truven Health Analytics MarketScan® electronic medical claims database were used to conduct two retrospective observational cohort studies, utilizing a cohort new-user design, comparing AMI risk between testosterone replacement therapy (TRT) and phosphodiesterase-5 inhibitors (PDE5is) in men treated for hypogonadism, and triptans versus other prescribed acute treatments for migraine in adults. All patients were enrolled continuously in a health plan (no enrollment gap > 31 consecutive days) for ≥ 1 year before index. Baseline period was defined as 365 days prior to index. Exposure was defined by prescription and outcome of interest was defined as occurrence of AMI. Using Cox proportional hazard models, primary analysis for the TRT cohort compared AMI risk between propensity score (PS)-matched TRT-treated and untreated patients; secondary analysis evaluated risk between PS-matched TRT-treated and PDE5i-treated patients. For the triptan cohort, primary analysis compared AMI/ischemic stroke risk between PS-matched triptan-treated and opiate-treated patients; secondary analysis evaluated risk between PS-matched triptan-treated and nonsteroidal anti-inflammatory drug (NSAID)-treated patients and PS-matched non-prescription-treated migraine patients and general patients. RESULTS: No significant association between TRT and AMI was observed among TRT-treated (N = 198,528, mean age 52.4 ± 11.4 years) versus PDE5i-treated men (N = 198,528, mean age 52.3 ± 11.5 years) overall (adjusted hazard ratio [aHR] 1.01; 95% CI 0.95-1.07; p = 0.80). Among patients with prior cardiovascular disease (CVD), risk of AMI was significantly increased for TRT-treated versus PDE5i-treated patients (aHR 1.13; 95% CI 1.03-1.25). The triptan study included three comparisons (triptans [N = 436,642] vs prescription NSAIDs [N = 334,152], opiates [N = 55,234], and untreated migraine [N = 1,168,212]), and a positive control (untreated vs general non-migraine patients [N = 11,735,009]). Analyses of MI risk in migraine patients prescribed triptans versus NSAIDs/opiates had mixed results: the point estimate ranged from 0.33 to 0.84 depending on chosen study window. CONCLUSIONS: Cardiovascular outcomes were not worse in hypogonadism patients with TRT versus PDE5i; however, a potential association with AMI was found in patients with prior CVD receiving TRT versus PDE5i. Findings pointed to a pseudo-protective effect of triptans versus untreated migraine patients or those potentially older and less healthy patients exposed to prescription NSAIDs or opiates. Triptan users should not be compared with those using other anti-migraine prescriptions when evaluating cardiovascular outcomes in migraine patients. Presence of high cardiovascular risks may contribute to channeling bias-healthier subjects being selected to receive treatment-highlighting the importance of choosing comparators wisely in observational studies.

Identification and implication of tissue-enriched ligands in epithelial-endothelial crosstalk during pancreas development.

Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. BMP7 and WNT7B, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and SEMA6D, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced BMP7 limited development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of BMP7 in the intercellular communications contributing to vessel development and organization during pancreas organogenesis.

Lasmiditan for Patients with Migraine and Contraindications to Triptans: A Post Hoc Analysis.

INTRODUCTION: As 5-HT1B receptor agonists, triptans produce vasoconstriction and have cardiovascular contraindications and precautions. Lasmiditan, a selective 5-HT1F receptor agonist, has a low affinity for 5-HT1B receptors, does not cause vasoconstriction, and is free of cardiovascular contraindications and precautions. The objective of this post hoc analysis was to evaluate the efficacy and safety of lasmiditan in patients with and without at least one triptan contraindication. METHODS: Patient subgroups, with and without triptan contraindications, were analyzed from pooled patient data from four randomized, double-blind, placebo-controlled clinical trials (SAMURAI, SPARTAN, CENTURION, and MONONOFU). Patients experiencing a single migraine attack of moderate or severe intensity were treated with lasmiditan 50 mg (SPARTAN and MONONOFU only), 100 mg, 200 mg, or placebo, and efficacy data were recorded in an electronic diary. RESULTS: Of 5704 patients, 207 (3.6%) patients had at least one contraindication to triptans. Overall subgroup analysis revealed that the effects of lasmiditan on pain freedom, pain relief, freedom from most bothersome symptom, disability freedom, and Patient Global Impression of Change at 2 h post-dose did not differ in patient groups with and without triptan contraindications. These outcomes generally showed a similar benefit pattern for lasmiditan in both subgroups, with all results being statistically significant in patients without contraindications, and pain relief being statistically significant in patients with contraindications. The safety and tolerability profiles of patients with triptan versus without triptan contraindications were similar, including dizziness in 18.3 to 22.8% and somnolence in 7.9 to 9.9% of patients at the highest dose of lasmiditan. CONCLUSIONS: In pooled analyses from four trials, patients with and without triptan contraindications did not differ in their patterns of lasmiditan efficacy. Lasmiditan may be a treatment option in patients with contraindications to triptans. TRIAL REGISTRATION NUMBERS: SAMURAI, NCT:02439320; SPARTAN, NCT:02605174; CENTURION, NCT:03670810; and MONONOFU, NCT:03962738.

The digiti quinti sign in hemiplegic migraine: An fMRI study.

BACKGROUND AND PURPOSE: The digiti quinti sign (DQS) consists of a wider angle between the fourth and fifth fingers (ANG) indicative of subtle hemiparesis that has been found interictally in hemiplegic migraine (HM), suggesting a permanent subtle motor dysfunction. The aim of this study was to find a possible cortical origin for the DQS using blood oxygen level dependent (BOLD) functional (f) MRI. METHODS: Eight HM patients and 13 controls entered the cross-sectional study. We examined hand dominance, performed handgrip tests with dynamometry, documented the DQS graphically in two consecutive sessions, and used BOLD-fMRI during a motor task specifically designed to measure the evoked activation in the motor cortex (M1). The brain activation at the symptomatic side was compared with the contralateral hemisphere and with both correspondent hemispheres in controls. RESULTS: Subjects had a normal neurological examination, except for DQS in all HM patients. The activation amplitude (beta values) and the cluster extension (mm3 ) of the activation area in M1 was smaller at the affected side. Besides, the cluster extension correlated negatively with the disease time span. The ANG was wider bilaterally in patients and the fMRI signals were reduced in the patient's group. CONCLUSION: The DQS, a relevant clinical finding in HM, indicates a disrupted cortical activation.

Global Overview of Response Rates in Patient and Health Care Professional Surveys in Surgery: A Systematic Review.

OBJECTIVE: Identify key demographic factors and modes of follow-up in surgical survey response. SUMMARY BACKGROUND DATA: Surveys are widely used in surgery to assess patient and procedural outcomes, but response rates vary widely which compromises study quality. Currently there is no consensus as to what the average response rate is and which factors are associated with higher response rates. METHODS: The National Library of Medicine (MEDLINE/PubMed) was systematically searched from Januray 1, 2007 until February 1, 2020 using the following strategy: (((questionnaire) OR survey) AND "response rate") AND (surgery OR surgical). Original survey studies from surgical(-related) fields reporting on response rate were included. Through one-way analysis of variance we present mean response rate per survey mode over time, number of additional contacts, country of origin, and type of interviewee. RESULTS: The average response is 70% over 811 studies in patients and 53% over 1746 doctor surveys. In-person surveys yield an average 76% response rate, followed by postal (65%) and online (46% web-based vs 51% email) surveys. Patients respond significantly more often than doctors to surveys by mail (P < 0.001), email (P = 0.003), web-based surveys (P < 0.001) and mixed mode surveys (P = 0.006). Additional contacts significantly improve response rate in email (P = 0.26) and web-based (P = 0.041) surveys in doctors. A wide variation in response rates was identified between countries. CONCLUSIONS: Every survey is unique, but the main commonality between studies is response rate. Response rates appear to be highly dependent on type of survey, follow-up, geography, and interviewee type.

The biomechanical basis of biased epithelial tube elongation in lung and kidney development.

During lung development, epithelial branches expand preferentially in a longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How this bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme, of preferential turnover of the extracellular matrix at the bud tips and of FGF signalling. There is also no evidence for actin-rich filopodia at the bud tips. Rather, we find epithelial tubes to be collapsed during early lung and kidney development, and we observe fluid flow in the narrow tubes. By simulating the measured fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis. This article has an associated 'The people behind the papers' interview.

Visual Perception in Migraine: A Narrative Review.

Migraine, the most frequent neurological ailment, affects visual processing during and between attacks. Most visual disturbances associated with migraine can be explained by increased neural hyperexcitability, as suggested by clinical, physiological and neuroimaging evidence. Here, we review how simple (e.g., patterns, color) visual functions can be affected in patients with migraine, describe the different complex manifestations of the so-called Alice in Wonderland Syndrome, and discuss how visual stimuli can trigger migraine attacks. We also reinforce the importance of a thorough, proactive examination of visual function in people with migraine.

Can you have a migraine aura without knowing it?

PURPOSE OF REVIEW: This review covers several aspects our understanding of episodic manifestations and unusual symptoms that may be associated with migraine aura. RECENT FINDINGS: The episodic manifestation of migraine aura is typically visual in nature, although five other types are currently recognized: sensory, speech and/or language, motor, brainstem, and retinal. Other transitory perceptions or experiences such as emotional, olfactory, or auditory have been reported as possible migraine auras. As underlined by the much higher reported prevalence of aura manifestation in individuals with professional knowledge of its possible manifestations, it appears that a number of migraine auras may remain unnoticed, unreported, or misdiagnosed. SUMMARY: Aura manifestations may be more common, complex, symptom-rich and variable than previously thought. Clinicians should proactively ask questions beyond those addressing visual symptoms when examining individuals with a potential diagnosis of migraine with aura.

Lasmiditan efficacy in migraine attacks with mild vs. moderate or severe pain.

OBJECTIVE: To evaluate the efficacy of lasmiditan (LTN) in treating migraine attacks of mild vs. moderate or severe pain intensity. METHODS: Pooled data from two single-attack, placebo-controlled studies (SAMURAI [NCT02439320] and SPARTAN [NCT02605174]), and a prospective, randomized, open-label study (GLADIATOR [NCT02565186]) were assessed. Efficacy measures included the proportion of attacks with 2-h pain freedom (PF), 2-h most bothersome symptom (MBS) freedom, and 24-h sustained pain freedom (SPF). Fisher's exact test was used to compare the proportion of PF, SPF, or MBS freedom outcomes among attacks treated at mild, moderate, or severe pain. RESULTS: In SAMURAI and SPARTAN, most treated attacks were of moderate (N = 2768) or severe (N = 1147) intensity, compared to mild (N = 65). Numerically greater 2-h PF and 24-h SPF response rates were observed in attacks treated at mild compared to moderate or severe pain. Analysis of GLADIATOR data included 273 (1.5%), 11,644 (65.1%), and 5948 (33.3%) attacks treated when pain was mild, moderate, and severe, respectively. In general, a significantly greater proportion of attacks treated at mild pain achieved 2-h PF and MBS freedom, as well as 24-h SPF. The incidence of treatment-emergent adverse events in LTN treatment groups were similar regardless of baseline head pain intensity. CONCLUSIONS: Data from two placebo-controlled, single-attack trials, and an open-label study including treatment of multiple attacks, suggested a tendency to relatively better efficacy outcomes when LTN treatment was initiated at mild vs. moderate to severe pain. Further research is needed to better understand the relationship of lasmiditan outcomes to the time of administration in the course of a migraine attack.

Delayed Surgery after Neoadjuvant Treatment for Rectal Cancer Does Not Lead to Impaired Quality of Life, Worry for Cancer, or Regret.

Non operative management of complete clinical responders after neoadjuvant treatment for rectal cancer enjoys an increasing popularity because of the increased functional outcome results. Even a near complete response can evolve in a cCR, and therefore further delaying response assessment is accepted. However, up to 40% of patients will develop a regrowth and will eventually require delayed surgery. It is presently unknown if and to what extent quality of life of these patients is affected, compared to patients who undergo immediate surgery. Between January 2015-May 2020, 200 patients were treated with neoadjuvant therapy of whom 94 received TME surgery. Fifty-one (59%) of 87 alive patients returned the questionnaires: 33 patients who underwent immediate and 18 patients who underwent delayed surgery. Quality of life was measured through the QLQ-C30, QLQ-CR29, and Cancer Worry Scale questionnaires. Regret to participate in repeated response assessment protocol was assessed through the Decision Regret Scale. Exploratory factor analysis (EFA) and a 'known groups comparison' was performed to assess QLQ questionnaires validity in this sample. Higher mean physical function scores (89.2 vs. 77.6, p = 0.03) were observed in the immediate surgery group, which lost significance after correction for operation type (p = 0.25). Arousal for men was higher in the delayed surgery group (20.0 vs. 57.1, p = 0.02). There were no differences between surgical groups for the other questionnaire items. Worry for cancer was lower in the delayed surgery group (10.8 vs. 14.0, p = 0.21). Regret was very low (12-16%). EFA reproduced most QLQ C-30 and CR29 subscales with good internal consistency. Quality of life is not impaired in patients undergoing delayed TME surgery after neoadjuvant treatment for rectal cancer. Moreover, there is very low regret and no increase in worry for cancer. Therefore, from a quality of life perspective, this study supports a repeated response assessment strategy after CRTx for rectal carcinoma to identify all complete responders.

Who was Pierre Marie?

In this manuscript we pay a tribute to Pierre Marie (1853-1940), highlighting his great contribution to medicine and neurology describing several diseases and syndromes. We mainly emphasize aspects of his personal life and personality traits. Considered one of the three greatest neurologists of the late nineteenth and early twentieth centuries, his brilliant career began at La Salpêtrière, followed by the development of a neurological school at Hospice Bicêtre. Pierre Marie had numerous disciples around the world, including Brazil, and published on various neurological and endocrinological themes. Back to La Salpêtrière, he concluded his professional life as a Neurology leader. However, after retirement, his demise was sad and lonely.

Who was Pierre Marie? / Quem foi Pierre Marie?

ABSTRACT In this manuscript we pay a tribute to Pierre Marie (1853-1940), highlighting his great contribution to medicine and neurology describing several diseases and syndromes. We mainly emphasize aspects of his personal life and personality traits. Considered one of the three greatest neurologists of the late nineteenth and early twentieth centuries, his brilliant career began at La Salpêtrière, followed by the development of a neurological school at Hospice Bicêtre. Pierre Marie had numerous disciples around the world, including Brazil, and published on various neurological and endocrinological themes. Back to La Salpêtrière, he concluded his professional life as a Neurology leader. However, after retirement, his demise was sad and lonely

RESUMO Neste manuscrito, prestamos homenagem a Pierre Marie (1853-1940), destacando sua grande contribuição para a medicina e a neurologia, descrevendo várias doenças e síndromes. Enfatizamos principalmente aspectos de sua vida pessoal e traços de personalidade. Considerado um dos três maiores neurologistas do final do século XIX e início do século XX, sua brilhante carreira começou em La Salpêtrière, seguida pelo desenvolvimento de uma escola de neurologia no Hospice Bicêtre. Pierre Marie teve numerosos discípulos em todo o mundo, incluindo o Brasil, e publicou sobre vários temas neurológicos e endocrinológicos. De volta a La Salpêtrière, ele concluiu sua vida profissional como líder da Neurologia. Porém, após aposentadoria, seu ocaso foi triste e solitário

Acute Migraine Prescription Patterns Vary by Baseline Cardiovascular Risk and Clinical Characteristics: A Real-World Evidence Study.

INTRODUCTION: Migraine is a debilitating neurological disease and one of the most common disorders in the world. Although the triptans, potent 5-HT1B/1D receptor agonists, are an effective and widely used acute treatment of migraine, few studies have assessed how their cardiovascular risk warnings could impact prescription patterns. This study characterized cardiovascular risk factors and other aspects of people with migraine in real-world settings and confirmed patterns of acute migraine care. METHODS: This retrospective study included five cohorts: people with migraine prescribed acute treatments [triptans, opiates, prescription nonsteroidal anti-inflammatory drugs (NSAIDs)], untreated people with migraine, and individuals without migraine diagnosis. Baseline demographic and clinical characteristics were used to develop and validate a 1-year myocardial infarction (MI) risk prediction model among untreated people with migraine. This validated prediction model generated disease risk scores (DRSs) for MI among untreated cohorts. RESULTS: Patients in the study included 436,642 prescribed a triptan, 55,234 prescribed opiates, and 334,152 prescribed NSAIDs; as well as 1,168,212 untreated persons with migraine and 11,735,009 nonmigraine participants. Those prescribed triptans were younger, had fewer cardiovascular risk factors and hospitalizations, and lower concomitant medication use than those in the NSAID and opiate cohorts. The distribution of the DRS showed that compared to patients prescribed NSAIDs (4.2%) or opiates (3.5%), a smaller proportion of patients prescribed triptans (1.3%) were at high risk for MI at 1 year (> 10%). CONCLUSION: People with migraine who had more cardiovascular risk factors and greater 1-year MI risk score were disproportionately prescribed opiates and NSAIDs compared to triptans. Future research should explore unmet needs for patients with disorders for which triptan therapy is contraindicated.

Parotidectomy-related facial nerve lesions: proposal for a modified Sunnybrook Facial Grading System.

OBJECTIVE: Facial nerve injury, affecting mainly the marginal mandibular branch, is the most frequent neurologic complication from parotidectomy. To test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy, emphasizing the marginal mandibular branch. METHODS: We reviewed the medical records of 73 post-parotidectomy patients (40 female, 18-84 years old, mean age 53.2 years) with facial nerve sparing, referred to the Department of Physical Therapy. All patients had parotid neoplasms or advanced skin cancer, and were followed by the principal author between 2006 and 2014. RESULTS: The muscles innervated by the marginal mandibular branch were the most frequently affected (72.6%), particularly in patients undergoing neck dissection (p = 0.023). The voluntary movement scores obtained with the modified system were significantly lower compared with the original version (p < 0.001). The best and worst scores were observed in patients with benign parotid tumors and skin cancer, respectively. Patients requiring neck dissection (p = 0.031) and resection of other structures (p = 0.021) had the lowest scores, evidenced only with the modified version. Patients with malignant tumors had significantly worse ratings, regardless of the Sunnybrook system version. The post-physiotherapy analysis involved 50 patients. The worst facial rehabilitation outcomes were related to the marginal mandibular branch function. CONCLUSION: The modified Sunnybrook Facial Grading System improved the marginal mandibular branch assessment, preserving the evaluation of other facial nerve branches.

Guillaume-Benjamin Duchenne: a miserable life dedicated to science.

Duchenne de Boulogne is known mainly by the disease eponymously named "Duchenne muscular dystrophy", or pseudohypertrophic muscular dystrophy, although some experts consider that the original description of this disease does not belong to him. Less well known are the facts related to the tragic death of his beloved wife shortly after the birth of his only child, the unjustifiable distance he was forced to keep from this son for more than 30 years, and of being humiliated and professionally despised by his peers. These events made the life of this physician, physiologist, researcher and inventor extremely arduous. We emphasize some aspects of the history of this man, his work and his life, a true genius of few friends.

Parotidectomy-related facial nerve lesions: proposal for a modified Sunnybrook Facial Grading System / Lesões do nervo facial relacionadas à parotidectomia: proposta de um sistema Sunnybrook de graduação facial modificado

ABSTRACT Facial nerve injury, affecting mainly the marginal mandibular branch, is the most frequent neurologic complication from parotidectomy. Objective To test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy, emphasizing the marginal mandibular branch. Methods We reviewed the medical records of 73 post-parotidectomy patients (40 female, 18-84 years old, mean age 53.2 years) with facial nerve sparing, referred to the Department of Physical Therapy. All patients had parotid neoplasms or advanced skin cancer, and were followed by the principal author between 2006 and 2014. Results The muscles innervated by the marginal mandibular branch were the most frequently affected (72.6%), particularly in patients undergoing neck dissection (p = 0.023). The voluntary movement scores obtained with the modified system were significantly lower compared with the original version (p < 0.001). The best and worst scores were observed in patients with benign parotid tumors and skin cancer, respectively. Patients requiring neck dissection (p = 0.031) and resection of other structures (p = 0.021) had the lowest scores, evidenced only with the modified version. Patients with malignant tumors had significantly worse ratings, regardless of the Sunnybrook system version. The post-physiotherapy analysis involved 50 patients. The worst facial rehabilitation outcomes were related to the marginal mandibular branch function. Conclusion The modified Sunnybrook Facial Grading System improved the marginal mandibular branch assessment, preserving the evaluation of other facial nerve branches.

RESUMO A lesão do nervo facial é a principal complicação neurológica relacionada às parotidectomias e, em geral, o ramo marginal mandibular é o mais frequentemente acometido. Objetivo Testar um Sistema Sunnybrook de Graduação Facial modificado (mS-FGS) como uma nova ferramenta para avaliar a função do nervo facial após a parotidectomia, enfatizando o ramo marginal mandibular. Métodos Estudo retrospectivo, baseado em prontuários de 73 casos (40 do sexo feminino, 18-84 anos, idade média = 53,2), submetidos à parotidectomia, com preservação do nervo facial. Todos os pacientes apresentavam neoplasias parotídeas ou câncer de pele avançado, e foram tratados pela autora principal entre 2006 e 2014. Resultados Neste estudo, os músculos inervados pelo ramo marginal mandibular foram os mais acometidos (72,6% dos casos), principalmente nos pacientes que realizaram esvaziamento cervical (p = 0,023). Os Escores de Movimento Voluntário obtidos pelo sistema modificado foram inferiores aos obtidos pelo original (p < 0,001). As melhores pontuações foram observadas em pacientes com tumores benignos parotídeos e os piores resultados, naqueles com câncer de pele. Pacientes que necessitaram de esvaziamento cervical e ressecção de outras estruturas, além da parótida, apresentaram escores menores (p = 0,031 e p = 0,021), evidenciados apenas pelo sistema modificado. Os tumores malignos geraram escores significativamente menores, independentemente do instrumento empregado. A análise pós fisioterapia envolveu 50 casos. Os piores resultados, após a intervenção fisioterapêutica, também foram observados nos músculos inervados pelo ramo marginal mandibular. Conclusão A avaliação da disfunção facial pós-parotidectomia, através do Sistema Sunnybrook com a modificação proposta permitiu uma apreciação mais detalhada do ramo marginal mandibular, sem prejuízo à avaliação dos demais ramos.