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Objective: To examine how individuals may learn headache trigger beliefs through sequential symbolic pairings of trigger candidates and headache attacks. Background: Learning from experience may be a major source of information about headache triggers. Little is known about learning‐based influences on the establishment of trigger beliefs. Methods: This cross‐sectional, observational study included N = 300 adults with headache who participated in a laboratory computer task. First, participants rated the chances (0%–100%) that encountering specific triggers would lead to experiencing a headache. Then, 30 sequential images with the presence or absence of a common headache trigger were presented alongside images representing the presence or absence of a headache attack. The primary outcome measure was the cumulative association strength rating (0 = no relationship to 10 = perfect relationship) between the trigger and headache using all previous trials. Results: A total of N = 296 individuals completed 30 trials for each of three triggers, yielding 26,640 total trials for analysis. The median [25th, 75th] association strength ratings for each of the randomly presented headache triggers were 2.2 [0, 3] for the Color Green, 2.7 [0, 5] for Nuts, and 3.9 [0, 8] for Weather Changes. There was a strong association between the "true" cumulative association strength and corresponding ratings. A 1‐point increase on the phi scale (i.e., no relationship to perfect relationship) was associated with a 1.20 (95% CI: 0.81 to 1.49, p < 0.0001) point increase in association strength rating. A participant's prior belief about the potency of a trigger affected their perceived rating of the accumulating evidence, accounting for 17% of the total variation. Conclusion: In this laboratory task, individuals appeared to learn trigger–headache associations through repeated exposures to accumulating symbolic evidence. Prior beliefs about the triggers appeared to influence ratings of the strength of relationships between triggers and headache attacks. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the benefits of deploying individual headache forecasting models using continuous updating with Bayesian methods. Background: The ability to reliably forecast headache attacks within an individual over time would enhance the study of attacks and allow preemptive treatment. However, deploying a suitable forecasting model in a clinical setting will likely involve several unique challenges related to heterogeneity in the predictor weights, limited or sparse data, and the need for a quick "warm‐up." The use of Bayesian methods offers solutions to each of these specific challenges. Methods: This was a post hoc analysis of a cohort study of individuals with episodic migraine attacks. Individuals completed daily diaries that allowed the estimation of several forecasting models, each using different types of ancillary information incorporated into formal prior probability distributions. An in silico analysis was conducted that mimicked the deployment of these models in a clinical‐like setting where the parameters of the models were continuously updated and evaluated each day using root mean square error (RMSE). Results: Individuals (N = 95) were followed for 50 days and contributed 3359 days of nonmissing diary data. During the observation period, there were 1293/3359 (38.5%) days with a headache attack. Self‐reported baseline headache frequency was associated with the corresponding predicted probability of future attacks, r = 0.15–0.39. At Day 25, the correlation between baseline information and predicted attack likelihood was r = 0.29 (95% CI: 0.09–0.47). Additionally, the use of prior probability distributions for model parameters improved the model fit, especially early in the deployment of the models (e.g., Day 5 RMSE 0.45 vs. 0.43). Models using informative prior probability distributions outperformed the models estimated without this information during the first 42 days of observation, although performance became more similar as more data were collected. Conclusions: This analysis demonstrates the value of Bayesian methods in using additional available information to improve forecasting model performance, especially early in the deployment of a forecasting model. To obtain the full value of such models or to apply any model in clinical settings, a model with adequate discrimination and calibration will be needed. [ABSTRACT FROM AUTHOR]

The article presents the discussion on interpreting all prediction models and the importance of validating any such model before implementing it in practice. Topics include analyzed using a combination of generalized linear models and machine learning methods; and poorly calibrated model leading to uninformed decisions such as overtreatment or the absence of needed interventions.

The article presents a study that discussed appraisal of the methods used in the study like aware of the details of the design of the study, different study designs involve different data collection methods, employ different analysis methods, and a precise understanding of the design. It discussed the challenges of conduct of observational research also describe common observational study designs and the use of such designs in headache research.

The article offers information on statistical methods in headache research including nature of reliability, use of reliability in headache research, and common problems related to reliability. It notes a model to describe sources of variability including classical test theory, inter-rater reliability, and internal consistency. It also notes some problems in reliability which include unreliability misinterpreted as lack of association and measures with unknown reliability.

The article discusses the descriptive statistics in scientific research which make up an important part of a research report since reporting all data from all participants is rarely realistic, providing an overview of the characteristics of the sample data and are used to communicate this information in a straightforward manner. It states that most descriptive statistics are relatively simple and easy to understand while some are more complicated and require careful consideration before use.

An editorial is presented which talks about statistical power calculations for determining the size of sample of research using null hypothesis testing, finding statistically significant difference by calculating the sample size and the effect size representing the magnitude. It talks about the correlation between variables, proportion of response and statisticians developing metrics which are known as standardized effect sizes.

Background Previous headache trigger studies have primarily utilized checklists to measure beliefs about triggers. While this work has defined the diversity of beliefs across headache sufferers, the strength of association and the frequency at which these triggers are encountered remain unexplored. Objective To measure the strength of association, frequency of encounter, and influences on trigger beliefs and perceptions using a laboratory assessment task. Methods This cross-sectional observational study, part of the HACOGS project, included adult current migraine, tension-type, or cluster headache sufferers. Participants rated the chances they would experience a headache if they were to encounter a specific trigger and the number of days per month they experience that trigger for 33 common triggers. Results All 300 participants contributed data on all triggers, with little missing data (1.2%). All triggers exhibited a high degree of inter-individual variability on the strength of association and encounter perceptions. Many triggers were perceived to be encountered daily (e.g., caffeine, air conditioning), and a full range of perceptions were observed for each trigger. Stress (75% chance of headache), missing a meal (60%), and dehydration (60%) were the triggers with the greatest potency beliefs. Only 8-15% of these beliefs were related to individual differences and 26-27% to the triggers themselves. Conclusions Participants expressed diverse beliefs and perceptions about the strength of many common headache triggers. Variation in these beliefs was not associated with individual differences or the triggers themselves. This finding supports the importance of measuring more than just the presence-absence of trigger beliefs. [ABSTRACT FROM AUTHOR]

We know little about the individual pain experience of patients recovering from surgery in the first weeks after hospital discharge. Here, we examine individual differences in the day-to-day experience after 2 major surgeries: lower limb total major joint arthroplasty (TJA) and cesarean delivery (CD). Fifty-five TJA patients and 157 CD patients were recruited to complete questionnaires and record their daily pain experiences after surgery. After hospital discharge, patients recorded their pain intensity once daily for 60 days (CD) or twice daily for 2 weeks, once daily for 2 weeks, weekly for 8 weeks, and monthly for 3 months (TJA). Pain scores were modeled using growth curve and Bayesian change-point models. Individual differences in the model fits were examined for evidence of day-to-day differences in pain. A log time model was the simplest model that fit the data, but examination of the residuals revealed high autocorrelation representing misspecification. A change-point model fit the data better and revealed that the form of recovery fundamentally changed between days 10 and 21 after surgery. These data add meaningfully to our understanding of recovery from pain after surgery by extending the period of frequent observations a few days after surgery to a 2-month period. These high time resolution data suggest that there is a typical experience of pain resolution after surgery, but that meaningful subpopulations of experience may exist. They also indicate that a transition occurs within 1 month after surgery from 1 pattern of change in pain over time to another. [ABSTRACT FROM AUTHOR]

Objective Compare intrathecal oxytocin, 100 µg to placebo on ongoing neuropathic pain and mechanical hyperalgesia and allodynia. Study design Randomized, controlled, double-blind cross-over Setting Clinical research unit Subjects Individuals aged 18 to 70 years with neuropathic pain for at least 6 months. Methods Individuals received intrathecal injections of oxytocin and saline, separated by at least 7 days, and ongoing pain in neuropathic area (VAS [visual analog scale]) and areas of hypersensitivity to von Frey filament and cotton wisp brushing were measured for 4 hours. Primary outcome was VAS pain in the first 4 hours after injection, analyzed by linear mixed effects model. Secondary outcomes were verbal pain intensity scores at daily intervals for 7 days and areas of hypersensitivity and elicited pain for 4 hours after injections. Results The study was stopped early after completion of 5 of 40 subjects planned due to slow recruitment and funding limitations. Pain intensity prior to injection was 4.75 ± 0.99 and modeled pain intensity decreased more after oxytocin than placebo to 1.61 ± 0.87 and 2.49 ± 0.87, respectively (P  = .003). Daily pain scores were lower in the week following injection of oxytocin than saline (2.53 ± 0.89 vs 3.66 ± 0.89; P  = .001). Allodynic area decreased by 11%, but hyperalgesic area increased by 18% after oxytocin compared to placebo. There were no study drug related adverse effects. Conclusion Although limited by the small number of subjects studied, oxytocin reduced pain more than placebo in all subjects. Further study of spinal oxytocin in this population is warranted. Trial registration This study was registered at ClinicalTrials.gov on 03/27/2014 (NCT02100956). The first subject was studied on 06/25/2014. [ABSTRACT FROM AUTHOR]

Objective To develop and validate a prediction model that forecasts future migraine attacks for an individual headache sufferer. Background Many headache patients and physicians believe that precipitants of headache can be identified and avoided or managed to reduce the frequency of headache attacks. Of the numerous candidate triggers, perceived stress has received considerable attention for its association with the onset of headache in episodic and chronic headache sufferers. However, no evidence is available to support forecasting headache attacks within individuals using any of the candidate headache triggers. Methods This longitudinal cohort with forecasting model development study enrolled 100 participants with episodic migraine with or without aura, and N = 95 contributed 4626 days of electronic diary data and were included in the analysis. Individual headache forecasts were derived from current headache state and current levels of stress using several aspects of the Daily Stress Inventory, a measure of daily hassles that is completed at the end of each day. The primary outcome measure was the presence/absence of any headache attack (head pain > 0 on a numerical rating scale of 0-10) over the next 24 h period. Results After removing missing data ( n = 431 days), participants in the study experienced a headache attack on 1613/4195 (38.5%) days. A generalized linear mixed-effects forecast model using either the frequency of stressful events or the perceived intensity of these events fit the data well. This simple forecasting model possessed promising predictive utility with an AUC of 0.73 (95% CI 0.71-0.75) in the training sample and an AUC of 0.65 (95% CI 0.6-0.67) in a leave-one-out validation sample. This forecasting model had a Brier score of 0.202 and possessed good calibration between forecasted probabilities and observed frequencies but had only low levels of resolution (ie, sharpness). Conclusions This study demonstrates that future headache attacks can be forecasted for a diverse group of individuals over time. Future work will enhance prediction through improvements in the assessment of stress as well as the development of other candidate domains to use in the models. [ABSTRACT FROM AUTHOR]

Background: Recovery from pain after surgery exhibits large interindividual variability, with very slow recovery equated to chronic pain. Surgical injury in the postpartum period modestly increases initial recovery after major nerve injury. In this study, the authors use a nerve injury that recovers over 2 to 3 months and apply growth curve modeling to further understand the effect of the postpartum period on speed of recovery.Methods: Withdrawal threshold to mechanical stimulus on the hind paw was determined in 41 Sprague-Dawley rats before and for 10 weeks after partial spinal nerve ligation. Age-matched male and female rats and postpartum females with pups or those separated from pups at delivery were studied. Growth curve analyses were applied to model recovery after surgery despite varying timing of measurements across groups and missing data, and these results were compared with those of two-way repeated-measures ANOVA.Results: The recovery time course was similar between males and females. In contrast, recovery was hastened in the postpartum groups, with nonoverlapping 95% CIs of modeled trajectories between days 6 and 66 after surgery. CIs were more precise at most time periods with growth curve analysis compared with ANOVA.Conclusions: The authors describe a method of analysis to quantify recovery from hypersensitivity after surgery in rats with several distinct advantages over traditionally used methods. Study results do not support a sex difference in trajectory of recovery but confirm and extend previous observations that injury at the time of obstetric delivery is associated with an abnormally rapid recovery. [ABSTRACT FROM AUTHOR]

The article presents an analysis of the efficacy of ubrogepant based on prior experience with triptans. It found that the efficacy and tolerability of ubrogepant did not differ for three classifications of participants based on historical experience with triptans. It mentions the heterogeneity of treatment effect analysis methods used here are very relevant to current headache medicine.

Objective To examine the potential influence of random measurement error on estimated rates of chronification and remission. Background Studies of headache chronification and remission examine the proportion of headache sufferers that move across a boundary of 15 headache days per month between 2 points in time. At least part of that apparent movement may represent measurement error or random variation in headache activity over time. Methods A mathematical simulation was conducted to examine the influence of varying degrees of measurement error on rates of chronic migraine onset and remission. Using data from the American Migraine Prevalence and Prevention Study, we estimated a starting distribution of headache days from 0 to 30 in the migraine population. Assuming various levels of measurement error, we then simulated 2 sets of data for Time 1 and Time 2. The 'individuals' in this study were assumed to have no real change in headache frequency from Time 1 to Time 2. The observed variations in headache frequency were those influenced by imputed random variance to resemble typical measurement error or natural variability. Using this simulation approach, we estimated the amount of chronification and remission rates that might be attributed simply to statistical artifacts such as unreliability or regression to the mean. Results As the degree of measurement error increased, the amounts of illusory chronification and remission increased substantially. For example, if the headache frequency of sufferers randomly varies by only 2 headache days each month due to chance alone, a substantial degree of illusory chronification (0.6% to 1.3%) and illusory remission (10.3% to 23.5%) rates are expected simply due to random variation. Conclusions Random variation, without real change, has the potential to influence estimated rates of progression and remission in longitudinal migraine studies. The magnitude of random variation needed to fully reproduce observed rates of progression and remission are implausibly large. Recommendations are offered to improve estimation of rates of progression and remission, reducing the influence of random variation. [ABSTRACT FROM AUTHOR]

Objectives To characterize the extent of measurement error arising from rounding in headache frequency reporting (days per month) in a population sample of headache sufferers. Background When reporting numerical health information, individuals tend to round their estimates. The tendency to round to the nearest 5 days when reporting headache frequency can distort distributions and engender unreliability in frequency estimates in both clinical and research contexts. Methods This secondary analysis of the 2005 American Migraine Prevalence and Prevention study survey characterized the population distribution of 30-day headache frequency among community headache sufferers and determined the extent of numerical rounding ('heaping') in self-reported data. Headache frequency distributions (days per month) were examined using a simplified version of Wang and Heitjan's approach to heaping to estimate the probability that headache sufferers round to a multiple of 5 when providing frequency reports. Multiple imputation was used to estimate a theoretical 'true' headache frequency. Results Of the 24,000 surveys, headache frequency data were available for 15,976 respondents diagnosed with migraine (68.6%), probable migraine (8.3%), or episodic tension-type headache (10.0%); the remainder had other headache types. The mean number of headaches days/month was 3.7 (standard deviation = 5.6). Examination of the distribution of headache frequency reports revealed a disproportionate number of responses centered on multiples of 5 days. The odds that headache frequency was rounded to 5 increased by 24% with each 1-day increase in headache frequency (odds ratio: 1.24, 95% confidence interval: 1.23 to 1.25), indicating that heaping occurs most commonly at higher headache frequencies. Women were more likely to round than men, and rounding decreased with increasing age and increased with symptoms of depression. Conclusions Because of the coarsening induced by rounding, caution should be used when distinguishing between episodic and chronic headache sufferers using self-reported estimates of headache frequency. Unreliability in frequency estimates is of particular concern among individuals with high-frequency (chronic) headache. Employing shorter recall intervals when assessing headache frequency, preferably using daily diaries, may improve accuracy and allow more precise estimation of chronic migraine onset and remission. [ABSTRACT FROM AUTHOR]

Objective In this study, we set out to determine whether individual headache sufferers can learn about the potency of their headache triggers (causes) using only natural experimentation. Background Headache patients naturally use the covariation of the presence-absence of triggers with headache attacks to assess the potency of triggers. The validity of this natural experimentation has never been investigated. A companion study has proposed 3 assumptions that are important for assigning causal status to triggers. This manuscript examines one of these assumptions, constancy in trigger presentation, using real-world conditions. Methods The similarity of day-to-day weather conditions over 4 years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in 9 regularly cycling headache sufferers, was examined using several available time series. An arbitrary threshold of 90% similarity using Gower's index identified similar days for comparison. Results The day-to-day variability in just these 3 headache triggers is substantial enough that finding 2 naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine vs not drinking wine) will only infrequently occur. Fluctuations in weather patterns resulted in a median of 2.3 days each year that were similar (range 0-27.4). Considering fluctuations in stress patterns and ovarian hormones, only 1.5 days/month (95% confidence interval 1.2-2.9) and 2.0 days/month (95% confidence interval 1.9-2.2), respectively, met our threshold for similarity. Conclusion Although assessing the personal causes of headache is an age-old endeavor, the great many candidate triggers exhibit variability that may prevent sound conclusions without assistance from formal experimentation or statistical balancing. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to evaluate the time-series relationships between stress, sleep duration, and headache pain among patients with chronic headaches. Sleep and stress have long been recognized as potential triggers of episodic headache (<15 headachedays/month), though prospective evidence is inconsistent and absent in patients diagnosed with chronic headaches (⩾15days/month). We reanalyzed data from a 28-day observational study of chronic migraine (n=33) and chronic tension-type headache (n=22) sufferers. Patients completed the Daily Stress Inventory and recorded headache and sleep variables using a daily sleep/headache diary. Stress ratings, duration of previous nights’ sleep, and headache severity were modeled using a series of linear mixed models with random effects to account for individual differences in observed associations. Models were displayed using contour plots. Two consecutive days of either high stress or low sleep were strongly predictive of headache, whereas 2days of low stress or adequate sleep were protective. When patterns of stress or sleep were divergent across days, headache risk was increased only when the earlier day was characterized by high stress or poor sleep. As predicted, headache activity in the combined model was highest when high stress and low sleep occurred concurrently during the prior 2days, denoting an additive effect. Future research is needed to expand on current findings among chronic headache patients and to develop individualized models that account for multiple simultaneous influences of headache trigger factors. [Copyright &y& Elsevier]

Sensory afferents in skin encode and convey thermal and mechanical conditions, including those that threaten tissue damage. A small proportion of skin, the glabrous skin of the distal extremities, is specialized to explore the environment in fine detail. Aside from increased innervation density, little is known regarding properties of mechanosensory afferents to glabrous skin in younger animals that explain the exquisite precision and high contrast in rapidly sampling physical structures, including those that threaten injury. To assess this, we obtained intact neuronal intracellular recordings in vivo from 115 mechanosensitive afferent neurons from lumbar and thoracic dorsal root ganglia in juvenile rats. Two characteristics were unique to glabrous skin: a threefold higher proportion of fast-conducting to slow-conducting afferents that were high-threshold mechanosensitive nociceptors compared with hairy skin and a twofold faster conduction velocity of fast-conducting nociceptors compared with hairy skin. Additionally differences were found in mechanical thresholds between glabrous skin and hairy skin for each fiber type. These differences reflect and help explain the rapid response of skin specialized to explore the physical environment. Additionally, these results highlight potential limitations of using passive electrical properties and conduction velocity alone to characterize primary afferents without knowledge of the skin type they innervated. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to determine the correlation between the variability of acute mixing of fentanyl in cerebrospinal fluid (CSF) and the block characteristics of intrathecal injection during combined spinal epidural CSE for labor. Using the combined spinal epidural method, fentanyl was injected in 56 women asking for analgesia for labor, after written informed consent. The results indicate that 1 minute after injection, there is no correlation between the local concentration of fentanyl in the cerebrospinal fluid and the onset or duration of labor analgesia. The study suggests that the distribution and/or clearance of intrathecally administered opioids is affected by the resting hemodynamic state.

Background: Tracheal intubation during sevoflurane induction is frequently facilitated with i.v. propofol. We designed a dose–response study to evaluate the intubating conditions, and the incidence and duration of apnea after i.v. propofol in children. Methods/Materials: Sixty healthy children were randomly assigned to 0, 0.5, 1, 2 or 3 mg·kg−1 i.v. propofol during sevoflurane/nitrous oxide anesthesia. Tracheal intubation was performed approximately 30 s after propofol by an anesthesiologist who was blind to the treatment. The anesthesiologist assessed the responses to laryngoscopy and intubation using a standardized scale. Incidence and duration of apnea after propofol as well as heart rate, and systolic blood pressure before and after laryngoscopy were recorded. Data were analyzed using one-way and repeated measuresanova, the Jonckheere–Terpstra test, and logistic regression, with P < 0.05 accepted. Results: The laryngoscopy score after 3 mg·kg−1 propofol was less than that after 0 mg·kg−1 ( P < 0.01) and 0.5 mg·kg−1 ( P < 0.05). Incidence of apnea after propofol 3 mg·kg−1, 8/10, was greater than after 0 mg·kg−1, 3/14 ( P < 0.011) and 0.5 mg·kg−1, 3/12 ( P < 0.03). Duration of apnea after 3 mg·kg−1 was greater than after 0 and 0.5 mg·kg−1 ( P < 0.01). The risk of apnea increased 1.83 fold for each 1 mg·kg−1 dose increase in propofol ( P < 0.01). Mean heart rate and systolic pressure decreased with the main effect, time. Conclusion: During sevoflurane/nitrous oxide anesthesia, propofol 3 mg·kg−1 provides superior intubating conditions with an increased incidence of and prolonged apnea compared with 0 and 0.5 mg·kg−1. [ABSTRACT FROM AUTHOR]

Headache is a chronic disease that occurs with varying frequency and results in varying levels of disability. To date, the majority of research and clinical focus has been on the role of biological factors in headache and headache-related disability. However, reliance on a purely biomedical model of headache does not account for all aspects of headache and associated disability. Using a biopsychosocial framework, the current manuscript expands the view of what factors influence headache by considering the role psychological (i.e., cognitive and affective) factors have in the development, course, and consequences of headache. The manuscript initially reviews evidence showing that neural circuits responsible for cognitive–affective phenomena are highly interconnected with the circuitry responsible for headache pain. The manuscript then reviews the influence cognitions (locus of control and self-efficacy) and negative affect (depression, anxiety, and anger) have on the development of headache attacks, perception of headache pain, adherence to prescribed treatment, headache treatment outcome, and headache-related disability. The manuscript concludes with a discussion of the clinical implications of considering psychological factors when treating headache. [ABSTRACT FROM AUTHOR]

Objective.—The present study examined the relationship between the diagnosis of migraine and self-reported sexual desire. Background.—There is evidence for a complex relationship between sexual activity and headache, particularly migraine. The current headache diagnostic criteria even distinguish between several types of primary headaches associated with sexual activity. Methods.—Members of the community or students at the Illinois Institute of Technology (N = 68) were administered the Brief Headache Diagnostic Interview and the Sexual Desire Inventory (SDI). Based on the revised diagnostic criteria established by the International Headache Society (ICHD-II), participants were placed in 1 of the 2 headache diagnostic groups: migraine (n = 23) or tension-type (n = 36). Results.—Migraine subjects reported higher SDI scores, and rated their own perceived level of desire higher than those suffering from tension-type headache. The presence of the symptom “headache aggravated by routine physical activity” significantly predicted an elevated SDI score. Conclusions.—Migraine headaches and sexual desire both appear to be at least partially modulated by serotonin (5-HT). The metabolism of 5-HT has been shown to covary with the onset of a migraine attack, and migraineurs appear to have chronically low systemic 5-HT. As sexual desire also has been linked to serotonin levels, the results are consistent with the hypothesis that migraine and sexual desire both may be modulated by similar serotonergic phenomena. [ABSTRACT FROM AUTHOR]

The majority of research conducted on headache has utilized cross-sectional designs which preclude the examination of dynamic factors and principally rely on group-level effects. The present article describes the application of an individual-oriented process model using time-series analytical techniques. The blending of a time-series approach with an interactive process model allows consideration of the relationships of intra-individual dynamic processes, while not precluding the researcher to examine inter-individual differences. The authors explore the nature of time-series data and present two necessary assumptions underlying the time-series approach. The concept of shock and its contribution to headache activity is also presented. The time-series approach is not without its problems and two such problems are specifically reported: autocorrelation and the distribution of daily observations. The article concludes with the presentation of several analytical techniques suited to examine the time-series interactive process model.(Headache2005;45:438-444) [ABSTRACT FROM AUTHOR]

Objective.—This preliminary study employed“within-patient” time-series methodology to examine headache symptom distributions (peak, sum) to assess predictability of day-to-day headache based on overall pattern, and to better characterize distributional properties of headache as they relate to study design and statistics in future research.Background.—Headache symptoms for a given patient may vary widely from one day to the next, ranging from days when the headache sufferer is asymptomatic to days when he or she is functionally disabled with severe headache. Although day-to-day variations are well recognized and appreciated clinically, headache is seldom studied using daily (eg, time-series) methodology that can elucidate potentially important individual and temporal variations. Instead, most headache research has relied upon cross-sectional designs aimed at examining group rather than individual effects which may serve to mask important individual differences. Additional within-patient time-series studies are needed to help identify symptom patterns, clinically meaningful patient subgroups, and relationships among precipitants, interventions, and outcomes. Such research would be aided by delineation of the distributional and temporal properties of key scales (eg, daily headache peak, sum). The present research provides such information derived from clinical samples of migraine and tension-type headache sufferers, laying a foundation for future time-series research.Methods.—Twenty-five migraine and 24 tension-type headache sufferers prospectively recorded daily headache activity for 1 month. Individual headache distributions were generated and examined individually and by diagnostic group. Predictability for headache was analyzed case by case and summarized by diagnostic group.Results.—The study determined the degree to which individual patients' headache activity distributions deviate from normality (skewness, kurtosis). For migraine and tension-type headache, individual patients' headache patterns were distinctly bimodal in nature. Notably, headache patterns with the lowest frequency were the most bimodal, and as frequency increased, the distributions tended to more closely approximate normal. Patterns were also detailed according to measures of predictability for headache (trends, autocorrelation). Generally, headache days tended to cluster together for both tension-type and migraine (positive autocorrelation) with headache on day 1 being a good predictor of headache on day 2.Conclusions.—To the authors' knowledge, this is the first study to utilize time-series methodology to characterize individual patients' headache distributions and temporal patterns and to empirically address predictability in this manner. The bimodal distributions noted among less frequent headache patterns would suggest that basic assumptions underlying the use of inferential statistics may be violated when examining intra-individual relationships. Time-series research promises to yield unique insights into patterns, precipitants, and impact of headache disorders, but future research must address both the large degree of individual differences in headache and the account for the unique types of statistical distributions among individual headache sufferers.(Headache2005;45:445-458) [ABSTRACT FROM AUTHOR]

The present article reviews the concept of statistical power analysis for research designs in headache. First, we present a basic overview of the concepts of statistical hypothesis testing. Then we discuss the elements of power analysis and, where appropriate, we address conventions for power calculations. We offer, for public use, an applied power calculator for two applications that are often encountered in headache research. We intend to help headache researchers design trials with adequate statistical power by offering a conceptual overview and the power calculators. In closing, we briefly address the implications of the present trend toward reporting point estimates of effect sizes with confidence levels.(Headache2005;45:414-418) [ABSTRACT FROM AUTHOR]

The effectiveness of EMG biofeedback training for tension headache has been well established. Previous studies evaluating changes in an average EMG activity score from pre- to posttreatment have not consistently found a relationship between a reduction in average EMG activity and headache improvement at posttreatment. The current study is a preliminary analysis of the utility of EMG variance as another possible mechanism of change. Frontalis EMG average activity and variances from 6 chronic tension-type headache sufferers who demonstrated significant improvement in headache activity at posttreatment (at least 70%) and 6 chronic tension-type headache sufferers who did not demonstrate improvement (less than 30%) were examined across 6 sessions of biofeedback treatment. The improved group demonstrated larger time-specific EMG variance in relation to mean EMG amplitudes during all treatment sessions. A dramatic decline in time-specific variance was observed during the later treatment sessions for improved participants; this pattern was not observed in the group who demonstrated little or no improvement. Results from the current study suggest that the inclusion of both average EMG activity and EMG variance may provide a more comprehensive measure to evaluate possible physiological changes responsible for improvement in headache activity following EMG biofeedback training. [ABSTRACT FROM AUTHOR]

Migraine, a common and disabling neurological disorder, is among the top reasons for outpatient visits to general neurologists. In addition to pharmacotherapy, lifestyle interventions are a mainstay of treatment. High-quality daily diary studies and intervention studies indicate intraindividual variations in the associations between lifestyle factors (such as stress, sleep, diet, and physical activity) and migraine attack occurrence. Behaviour change interventions can directly address overlapping lifestyle factors; combination approaches could capitalise on multiple mechanisms. These findings provide useful directions for integration of lifestyle management into routine clinical care and for future research. [ABSTRACT FROM AUTHOR]

Background: This study investigated the mechanism of action of atogepant, a small-molecule CGRP receptor antagonist recently approved for the preventive treatment of episodic migraine, by assessing its effect on activation of mechanosensitive C- and Aδ-meningeal nociceptors following cortical spreading depression. Methods: Single-unit recordings of trigeminal ganglion neurons (32 Aδ and 20 C-fibers) innervating the dura was used to document effects of orally administered atogepant (5 mg/kg) or vehicle on cortical spreading depression-induced activation in anesthetized male rats. Results: Bayesian analysis of time effects found that atogepant did not completely prevent the activation of nociceptors at the tested dose, but it significantly reduced response amplitude and probability of response in both the C- and the Aδ-fibers at different time intervals following cortical spreading depression induction. For C-fibers, the reduction in responses was significant in the early phase (first hour), but not delayed phase of activation, whereas in Aδ-fibers, significant reduction in activation was apparent in the delayed phase (second and third hours) but not early phase of activation. Conclusions: These findings identify differences between the actions of atogepant, a small molecule CGRP antagonist (partially inhibiting both Aδ and C-fibers) and those found previously for fremanezumab, a CGRP-targeted antibody (inhibiting Aδ fibers only) and onabotulinumtoxinA (inhibiting C-fibers only)- suggesting that these agents differ in their mechanisms for the preventive treatment of migraine. [ABSTRACT FROM AUTHOR]

The article offers the author's view on the Type 1 error rate in headache research. The author states that Type 1 error is the probability that null hypothesis is rejected when it is true. The author cites that the error sets a consistent threshold for judging the statistical inferences. The author also mentions the type of error sets which must be considered including pre-comparison, family wise, and experiment wise.

The author reflects on the process of reviewing the statistical analyses in a manuscript which is presented for publication. He suggests that the process is a daunting one. He argues that good statistical reporting in manuscripts makes the statistical analysis review process more accurate and easier for the reviewer.

Objective: To evaluate pain medication beliefs in a community sample of individuals with headache. Background: Previous studies of medication adherence for individuals with headache have identified a high rate of prescription nonfulfillment, frequent medication discontinuation, and widely varying levels of medication‐related satisfaction. Still, there is a limited understanding of how these individuals view their medications and their relationships with health‐care providers. Insight into these perceptions could prove useful in explaining medication adherence behaviors. Methods: In this secondary analysis of a cross‐sectional study, data from N = 215 adults with headache were analyzed. Participants completed the Pain Medication Attitudes Questionnaire (PMAQ), Center for Epidemiologic Studies Depression Scale (CES‐D), State–Trait Anxiety Inventory Form Y‐2, Weekly Stress Inventory Short Form, and Migraine Disability Scale. These participants also provided a list of their current pain medications. Results: Using the PMAQ, participants could be characterized as having medication beliefs that were "trusting and unconcerned" (n = 83/215 [38.6%]), "skeptical and somewhat worried" (n = 99/215 [46.0%]), or "skeptical and concerned" (n = 33/215 [15.3%]). Individuals with skeptical and concerned beliefs expressed elevated concerns (z > 1.15) about side effects, scrutiny, perceived need, tolerance, withdrawal, and addiction. Individuals who were trusting and unconcerned expressed low levels (z < −0.40) of these beliefs. Increasing levels of mistrust and medication concerns were correlated with higher depression scores on the CES‐D, with values ranging from r = 0.23 to r = 0.38. Conclusions: Subgroups of pain medication beliefs were identified, including two groups of patients with at least some concerns about their medical providers. Beliefs ranged from a lack of concern about using pain medications to worries about scrutiny and harm. It is unclear if poor experiences with pain medications cause these beliefs or if they prevent individuals from effectively utilizing medications. Additionally, more negative beliefs about pain medications were associated with more depressive symptoms. Plain Language Summary: Studies have shown that while most people with headaches use medicines to treat their attacks, they are not always happy with these medicines, and they often do not fill their prescriptions. To better understand why this may be, we looked at beliefs about medication in 215 individuals who have headaches and experience using pain medicines. We found that some individuals reported little concern about their medications, while others reported high levels of worry about side effects or becoming dependent on them. [ABSTRACT FROM AUTHOR]

An editorial is presented on the confidence intervals represent a range of values that are plausible for an unknown parameter of interest. Topics include the confidence intervals have been increasing in popularity as a key element of research reporting and are routinely calculated by statistical software packages, and the confidence intervals are commonly seen in research reports are complex nature can make understanding and applying them difficult.

The article discusses in headache research, frequentist inferences have used, methods exist and deserve consideration. Topics include introduction to Bayesian inference continues the series of methods and statistics primers in the Journal; and the idea of probability has an interesting history, and the study of probability has a mature branch of mathematics.

An editorial is presented on hypothesis testing, is a form of inferential statistics that allows us to draw conclusions about an entire population based on a representative sample. Null Hypothesis, based hypothesis testing begins with the formulation of the null hypothesis. Fisher's Approach method allows the estimation of the probability of observing a test result at least as extreme as the test statistic, assuming that the null hypothesis is true.

Objective: Using experimental, yet realistic, headache calendars, this laboratory study evaluated the ability of individuals to identify the degree of association between triggers and headaches. Background: Individuals with headache often record daily diaries or calendars to identify their patterns of triggers. Methods: This cross‐sectional, observational study included adults with migraine, tension‐type, or cluster headache who had ever experienced more than 5 attacks. Participants (N = 300) were presented with headache calendars and asked to rate the strength of the relationship (how strongly one causes the other) between 3 experimental triggers (high stress, poor sleep, and cinnamon) and headache using a 0 ("no relationship") to 10 ("perfect relationship") scale for each calendar. Results: Calendars with a high positive correlation between trigger and headache had higher participant ratings than those with low correlations. The median [25th, 75th] of ratings for each correlation level was low correlation: 1 [0, 4], medium: 4 [2, 5], and high: 5 [4, 8], P <.0001. However, participants appeared to ignore negative associations (ie, trigger present with no headache) and rated calendars with more headache days as having higher associations, regardless of the true relationship. The ratings for 2, 6, and 26 headache days were 1 [0, 3], 4 [1, 6], and 8 [0, 10], respectively (P <.0001). Participants' previous beliefs about the triggers also affected their ratings (average correlation across triggers: r = 0.25, P <.0001). Conclusions: This laboratory task supports the notion that individuals with headache are able to identify the association between headaches and triggers using headache calendars. However, these judgments can be biased by the individuals' previous beliefs about the trigger and by the degree of headache activity. [ABSTRACT FROM AUTHOR]

Pain and physical activity are tightly intertwined. Although their relationship has been explored in chronic pain conditions, we know little about the pattern of recovery in activity and its short- and long-term relationship with pain after surgery. We recruited 103 women undergoing elective cesarean delivery and acquired daily pain assessments and hourly steps in 98 of them for 2 months after surgery. Compliance was good, with 78% of subjects missing less than 7 days of activity. Study personnel required daily checking for compliance and 20 minutes per subject per week in study. Activity increased over the first 2 postoperative months in a log(time) manner. The slope of each modeled individual curve for activity was inversely correlated (r = -0.54; P < 0.0001) with worst daily pain. After removing these 2-month trends, pain and activity within an individual day were negatively associated with each point increase in pain being inversely associated with -119 steps (95% confidence interval [CI] = -214 to -25; P = 0.013). A patient's previous experience of pain was not associated with current activity as well as current activity was not associated with future pain scores. These data, although limited by the study of a single operation in a unique social circumstance with low risk of chronic postsurgical pain, demonstrate feasibility of measuring hourly activity for 2 months after surgery. Recovery from pain and inactivity are tightly correlated, and the negative relationship between within-day pain and activity without interday carryover relationships is in stark contrast to findings in chronic pain conditions. [ABSTRACT FROM AUTHOR]

The article discusses a study on whether headache triggers predict the cessation of an attack. The patients who participated in the study were asked to record headache activity and perceived stress, a headache trigger, in a diary for one month. The researchers considered the course of headache activity for either days after an attack had stopped or days after an attack had started to determine the impact of stress on eliciting a new attack or ceasing an existing attack.

We know very little about the change in pain in the first 2 months after surgery. To address this gap, we studied 530 women scheduled for elective cesarean delivery who completed daily pain diaries for 2 months after surgery through text messaging. Over 82% of subjects missed fewer than 10 diary entries and were included in the analysis. Completers were more likely to be Caucasian, nonsmokers, and with fewer previous pregnancies than noncompleters. Daily worst pain intensity ratings for the previous 24 hours were fit to a log(time) function and allowed to change to a different function up to 3 times according to a Bayesian criterion. All women had at least one change point, occurring 22 ± 9 days postoperatively, and 81% of women had only one change, most commonly to a linear function at 0 pain. Approximately 9% of women were predicted to have pain 2 months after surgery, similar to previous observations. Cluster analysis revealed 6 trajectories of recovery from pain. Predictors of cluster membership included severity of acute pain, perceived stress, surgical factors, and smoking status. These data demonstrate feasibility but considerable challenges to this approach to data acquisition. The form of the initial process of recovery from pain is common to all women, with divergence of patterns at 2 to 4 weeks after cesarean delivery. The change-point model accurately predicts recovery from pain; its parameters can be used to assess predictors of speed of recovery; and it may be useful for future observational, forecasting, and interventional trials. [ABSTRACT FROM AUTHOR]

The article discusses the study "Femoral Nerve Block Improves Analgesia Outcomes After Total Knee Arthroplasty," by J. E. Paul, A. Arya, L. Hurlbert, J. Cheng, L. Thabane, A. Tidy and Y. Murthy, published within the issue. The study confirmed that a good alternative to patient-controlled analgesia alone or epidural for postoperative analgesia in patients having total knee arthroplasty is FNB with patient-controlled analgesia. Two trials which did not meet the criteria for inclusion in the meta-analysis study of Paul et al., are highlighted.

The author reflects on the results of a study published within the issue that did not follow the original plans of researchers. He explains that the study shows the potential benefits in reducing major adverse cardiac events by using a continuous insulin infusion against a standard intermittent insulin bolus. He states that the interpretation of a clinical trial can be challenging under the best of circumstances but the authors of the study make the interpretation a trial.

Presents a letter to the editor about the Premonitory Symptoms (Prodrome): A Tertiary Care Study of 893 Migraineurs.

Objectives: This secondary analysis evaluated the information content exhibited by various measurement strategies of commonly perceived causes, or "triggers," of headache attacks. Background: When evaluating triggers of primary headache attacks, the variation observed in trigger candidates must be measured to compare against the covariation in headache activity. Given the numerous strategies that could be used to measure and record headache trigger variables, it is useful to consider the information contained in these measurements. Methods: Using previously collected data from cohort and cross‐sectional studies, online data sources, and simulations, the Shannon information entropy exhibited by many common triggers was evaluated by analyzing available time‐series or theoretical distributions of headache triggers. The degree of information, reported in bits, was compared across trigger variables, measurement strategies, and settings. Results: A wide range of information content was observed across headache triggers. Due to lack of variation, there was little information, near 0.00 bits, in triggers like red wine and air conditioning. Most headache triggers exhibited more information when measured using an ordinal scale of presence/degree (e.g., absent, mild, moderate, severe) versus a present/absent binary coding. For example, the trigger "joy" exhibited 0.03 bits when assessed using binary coding but 1.81 bits when coded using an ordinal scale. More information was observed with the use of count data (0.86 to 1.75 bits), Likert rating scales (1.50 to 2.76 bits), validated questionnaires (3.57 to 6.04 bits), weather variables (0.10 to 8.00 bits), and ambulatory monitoring devices (9.19 to 12.61 bits). Conclusions: Although commonly used, all binary‐coded measurements contain ≤1.00 bit of information. Low levels of information in trigger variables make associations with headache activity more difficult to detect. Assessments that balance information‐rich measurements with reasonable participant burden using efficient formats (e.g., Likert scales) are recommended to enhance the evaluation of the association with headache activity. [ABSTRACT FROM AUTHOR]