Objective – To briefly describe the history of and available data on anti‐calcitonin gene‐related peptide (CGRP) therapies for headache.
Background – CGRP was proposed as a target for primary ...headache therapies. Translational research involved moving from delineating the relationships between CGRP and primary headaches and the clinical development of anti‐CGRP treatments. The first anti‐CGRP treatment, an intravenous CGRP‐receptor antagonist or gepant, olcegepant, was described as effective in terminating migraines in humans in 2004.
Methods – The author briefly reviews some of the pathophysiology and translational research that led to the development of the gepants initially and then subsequently to the anti‐CGRP and anti‐CGRP receptor monoclonal antibodies. All accessible randomized controlled trials, s, platform presentations, and press releases on the monoclonal antibody trials are summarized. The trajectory from bench research to the approval of the first anti‐CGRP receptor monoclonal antibody for clinical use in migraine prevention, erenumab, is discussed, as well as potential clinical uses of the anti‐CGRP treatments.
Results – The US Food and Drug Administration (FDA) approved erenumab, an anti‐CGRP receptor monoclonal antibody, for prevention of migraine May 17, 2018. At the time of this writing (May 2018), 2 other anti‐CGRP monoclonal antibodies have been submitted to the FDA for the indication of prevention of migraine, galcanezumab and fremanezumab. Galcanezumab has reportedly shown effectiveness in preventing episodic cluster headache as well, although has not yet been submitted to the FDA for this indication. Eptinezumab will likely be submitted to the FDA for prevention of migraine later in 2018. Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for acute treatment of migraine, but have not yet been submitted to the FDA for this indication.
Conclusions – The development of anti‐CGRP therapies opens a new era in the acute and preventive treatment of primary headache disorders.
A growing literature explores abusive supervision, nonphysical forms of hostility perpetrated by managers against their direct reports. However, researchers have used different terminology to explore ...phenomena that overlap with abusive supervision, and extant research does not devolve from a unifying theoretical framework. These problems have the potential to undermine the development of knowledge in this important research domain. The author therefore provides a review of the literature that summarizes what is known about the antecedents and consequences of abusive supervision, provides the basis for an emergent model that integrates extant empirical work, and suggests directions for future research.
Genetic sensitivity to the bitter taste of phenylthiocarbamide and 6-n-propylthiouracil (PROP) is a well-studied human trait. It has been hypothesized that this phenotype is a marker for individual ...differences in taste perception that influence food preferences and dietary behavior with subsequent links to body weight and chronic disease risk. Steady progress has been made over the past several decades in defining the involvement of this phenotype and its underlying gene, TAS2R38, in this complex behavioral pathway. However, more work needs to be done to fully determine its overall nutritional and health significance. The primary goal of this review is to assess our current understanding of the role of the PROP bitter taste phenotype in food selection and body weight in both children and adults. A brief history of the field is included and controversies surrounding the use of different PROP screening methods are addressed. The contribution of other receptors (both bitter and nonbitter) to human taste variation is also discussed.
Objective
To evaluate non‐invasive vagus nerve stimulation (nVNS) as an acute cluster headache (CH) treatment.
Background
Many patients with CH experience excruciating attacks at a frequency that is ...not sufficiently addressed by current symptomatic treatments.
Methods
One hundred fifty subjects were enrolled and randomized (1:1) to receive nVNS or sham treatment for ≤1 month during a double‐blind phase; completers could enter a 3‐month nVNS open‐label phase. The primary end point was response rate, defined as the proportion of subjects who achieved pain relief (pain intensity of 0 or 1) at 15 minutes after treatment initiation for the first CH attack without rescue medication use through 60 minutes. Secondary end points included the sustained response rate (15‐60 minutes). Subanalyses of episodic cluster headache (eCH) and chronic cluster headache (cCH) cohorts were prespecified.
Results
The intent‐to‐treat population comprised 133 subjects: 60 nVNS‐treated (eCH, n = 38; cCH, n = 22) and 73 sham‐treated (eCH, n = 47; cCH, n = 26). A response was achieved in 26.7% of nVNS‐treated subjects and 15.1% of sham‐treated subjects (P = .1). Response rates were significantly higher with nVNS than with sham for the eCH cohort (nVNS, 34.2%; sham, 10.6%; P = .008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; P = .48). Sustained response rates were significantly higher with nVNS for the eCH cohort (P = .008) and total population (P = .04). Adverse device effects (ADEs) were reported by 35/150 (nVNS, 11; sham, 24) subjects in the double‐blind phase and 18/128 subjects in the open‐label phase. No serious ADEs occurred.
Conclusions
In one of the largest randomized sham‐controlled studies for acute CH treatment, the response rate was not significantly different (vs sham) for the total population; nVNS provided significant, clinically meaningful, rapid, and sustained benefits for eCH but not for cCH, which affected results in the total population. This safe and well‐tolerated treatment represents a novel and promising option for eCH. ClinicalTrials.gov identifier: NCT01792817.
We invoke the person–environment fit paradigm to examine on a daily basis follower affective, attitudinal, and behavioral responses to transformational leadership needed and received. Results from ...two experience sampling method (ESM) studies suggested that positive affect was higher on days when transformational leadership received fit follower needs (compared to days when the amount received was deficient or in excess of follower needs) and on days when absolute levels of fit was higher. We also found that positive affect mediated the within-person effects of transformational leadership needed and received on subordinates’ daily work attitudes (Studies 1 and 2) and organizational citizenship behaviors (Study 2). Supplemental analyses in Study 2 revealed that subordinates need more transformational leadership when they experience more challenge stressors, face greater uncertainty at work, and perform more meaningful work.
Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior ...tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli.
This manuscript explores cross-cultural differences in reactions to perceived abusive supervision. Based on an integration of fairness heuristic theory with principles about cross-cultural ...differences in the importance of hierarchical status, we theorize that subordinates from the Anglo culture perceive and react to abusive supervision more negatively than subordinates from the Confucian Asian culture. The predictions were tested within two field studies. Study 1 results show that culture moderated the direct effect of perceived abusive supervision on interpersonal justice and the indirect effects of perceived abusive supervision (via interpersonal justice) on subordinates’ trust in the supervisor and work effort. The negative effects of perceived abusive supervision were stronger for subordinates within the Anglo versus the Confucian Asian culture; subordinates from Anglo culture compared with Confucian Asian culture perceived abusive supervision as less fair. Perceived abusive supervision indirectly and negatively influenced subordinates’ trust in the supervisor and work effort. Study 2 replicated the findings from Study 1 and extended them to show culture (Anglo vs. Confucian culture) moderated the effects because it influences subordinates’ power distance orientation.
Objective
To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine.
Background
sTMS was originally developed for the ...acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention.
Methods
The
e
Neura
S
pringTMS
P
ost-Market
O
bservational
U
.S.
S
tudy of Migrain
e
(ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity.
Results
Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (−0.63 days) (p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher (p < 0.0001) than the performance goal (20%). There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4) (p < 0.0001), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days) (p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events.
Conclusions
This open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention.
Trial registration number
NCT02357381
Drawing on justice theory, I examined the consequences of abusive supervisor behavior. As expected, subordinates who perceived their supervisors were more abusive were more likely to quit their jobs. ...For subordinates who remained with their jobs, abusive supervision was associated with lower job and life satisfaction, lower normative and affective commitment, and higher continuance commitment, conflict between work and family, and psychological distress. Organizational justice mediated most of these effects, and job mobility moderated some of the deleterious effects of abusive supervision.
Making mistakes is an inevitable part of leadership, but little is known about how and when leaders benefit from reflecting on their missteps. In this paper, we propose that mistakes, when reflected ...upon, have the potential to increase a leader's expressed humility. We detail how having leaders recall past mistakes can help them formulate plans for learning and encourage them to express humility. We also argue that this positive relationship is strengthened when leaders have a promotion focus. We detail downstream benefits, as increased levels of leaders’ expressed humility are expected to increase their teams’ improvement‐oriented behaviors and, subsequently, team performance. Across multiple studies and using varied methods (i.e., scenario‐based experiments with 955 managerial leaders, a laboratory experiment with 210 student leaders and team members, and a daily field experiment with 85 managers), we empirically test the proposed relationships. Our studies contribute to the literature by identifying leaders’ recall of learning from mistakes as an important intervention to elicit their expressed humility.
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