A survey of patient practices regarding leftover antibiotics reveals a potential source of antibiotic overuse.

Taking leftover prescribed antibiotics without consulting a healthcare professional is problematic for the efficacy, safety, and antibiotic stewardship. We conducted a cross-sectional survey of adult patients in English and Spanish between January 2020 and June 2021 in six safety-net primary care clinics and two private emergency departments. We assessed the reasons for stopping prescribed antibiotics early and what was done with the leftover antibiotics. Additionally, we determined 1) prior leftover antibiotic use, 2) intention for future use of leftover antibiotics, and 3) sociodemographic factors. Of 564 survey respondents (median age of 51), 45% (251/564) reported a history of stopping antibiotics early, with 171/409 (42%) from safety net and 80/155 (52%) from the private clinics. The most common reason for stopping prescribed antibiotics early was "because you felt better" (194/251, 77%). Among survey participants, prior use of leftover antibiotics was reported by 149/564 (26%) and intention for future use of leftover antibiotics was reported by 284/564 (51%). In addition, higher education was associated with a higher likelihood of prior leftover use. Intention for future use of leftover antibiotics was more likely for those with transportation or language barriers to medical care and less likely for respondents with private insurance. Stopping prescribed antibiotics early was mostly ascribed to feeling better, and saving remaining antibiotics for future use was commonly reported. To curb nonprescription antibiotic use, all facets of the leftover antibiotic use continuum, from overprescribing to hoarding, need to be addressed.

Health care resource utilization and costs associated with diagnosed medication overuse headache and potential acute medication overuse in individuals with migraine.

OBJECTIVE: Estimate health care resource utilization and costs associated with medication overuse headache and potential acute medication overuse. METHODS: A retrospective analysis was conducted with Clinformatics Data Mart data (1 January 2019-31 December 2019) that included continuously enrolled commercially insured adults with migraine (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code G43.xxx). Medication overuse headache was defined as ≥1 inpatient or ≥2 outpatient claims with an ICD-10-CM code G44.41/40 (drug-induced headache). Potential acute medication overuse was defined as possessing sufficient medication for >10 mean treatment days/month for ergots, triptans, opioids, or combination analgesics or >15 mean cumulative days/month for simple prescription analgesics (e.g., acetaminophen, aspirin, other non-opioid analgesics) for >6 consecutive months. All-cause and migraine-related health care resource utilization and costs were compared after adjusting for demographic and clinical characteristics. RESULTS: Among 90,017 individuals with migraine, the frequency of medication overuse headache/potential acute medication overuse was 12.6% (diagnosed medication overuse headache: 0.6%; potential acute medication overuse: 12.1%). Adjusted all-cause total costs ($31,235 vs $21,486; difference: $9,749 [P < 0.001]) and adjusted migraine-related total costs ($9,770 vs $6,207; difference: $3,563 [P < 0.001]) were higher in the medication overuse headache/potential acute medication overuse group versus those without medication overuse headache/potential acute medication overuse. CONCLUSIONS: Individuals with diagnosed medication overuse headache/potential acute medication overuse had higher all-cause and migraine-related health care resource utilization and costs versus individuals without medication overuse headache/potential acute medication overuse, suggesting that improved migraine management is needed to reduce associated costs.

Functional impairment of chronic migraine with medication overuse: Secondary analysis from the Medication Overuse Treatment Strategy (MOTS) trial.

BACKGROUND: Chronic migraine exerts substantial negative impacts on daily functioning. Efforts to manage impaired functioning may result in medication overuse, which contributes to the worsening profile and chronification of migraine. The Migraine Functional Impact Questionnaire (MFIQ) is a recently developed measure assessing the impact of migraine on physical, social, and emotional function. OBJECTIVE: The objective of this analysis was to assess changes in MFIQ scores following initiation or modification of migraine preventive medication and determine if changes in function are associated with changes in other aspects of migraine burden, such as headache frequency, headache intensity, and symptoms of anxiety and depression. METHODS: This is a secondary analysis of data from the Medication Overuse Treatment Strategy (MOTS) trial, a prospective pragmatic clinical trial that investigated two treatment strategies for those with chronic migraine and medication overuse. Data from both treatment arms were pooled and analyzed using a pre-post design. Prior to and 12 weeks following initiation or modification of migraine preventive medication, participants completed a series of questionnaires that captured migraine characteristics, medication use, migraine-related physical impairment (MFIQ), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire 9 [PHQ-9]) symptoms. Changes from baseline in all measures were assessed using the paired t-test. Relationships between changes in MFIQ scores and other measures were assessed using linear regression. Multivariable modeling was performed to determine which additional variables contributed to the change in MFIQ beyond that already explained by an individual variable. Model terms were selected by using elastic net regularization. Only those participants who completed the baseline and 12-week MFIQ were included in this analysis. RESULTS: Of the 537 patients, 88.2% were female, and the average age was 45 years (standard deviation 13). The mean frequency of days with moderate-to-severe headache improved 39.2% from 13.5 per 30 days at baseline to 8.1 per 30 days at week 12. The mean MFIQ Usual Activities Global score improved by 15.0 points (on a 100-point scale). All five domains (Usual Activities Global, Usual Activities, Social Function, Emotional Function, Physical Function) of the MFIQ improved by a mean of at least 13.0 points. Changes in PHQ-9 score, followed by changes in headache frequency, had the strongest associations with change in all domains of the MFIQ. CONCLUSIONS: The negative impact of chronic migraine with medication overuse on physical, social, and emotional functioning substantially lessened following initiation or modification of migraine preventive medication. Improved functioning, as measured by the MFIQ, was most strongly associated with reductions in depression scores and headache frequency, highlighting the importance of recognizing and monitoring changes in depressive symptoms, in addition to headache frequency and functional impairment, when evaluating response to preventive medications.

Harris Poll Migraine Report Card: population-based examination of high-frequency headache/migraine and acute medication overuse.

BACKGROUND: Migraine is a disabling neurologic disease that can fluctuate over time in severity, frequency, and acute medication use. Harris Poll Migraine Report Card was a US population-based survey to ascertain quantifiable distinctions amongst individuals with current versus previous high-frequency headache/migraine and acute medication overuse (HFM+AMO). The objective of this report is to compare self-reported experiences in the migraine journey of adults with HFM+AMO to those who previously experienced HFM+AMO but currently have a sustained reduction in headache/migraine frequency and acute medication use. METHODS: An online survey was available to a general population panel of adults (≥18 years) with migraine per the ID Migraine™ screener. Respondents were classified into "current HFM+AMO" (within the last few months had ≥8 headache days/month and ≥10 days/month of acute medication use; n=440) or "previous HFM+AMO" (previously had HFM+AMO, but within the last few months had ≤7 headache days/month and ≤9 days/month of acute medication use; n=110). Survey questions pertained to demographics, diagnosis, living with migraine, healthcare provider (HCP) communication, and treatment. RESULTS: Participants in the current HFM+AMO group had 15.2 monthly headache days and 17.4 days of monthly acute medication use in last few months compared to 4.2 and 4.1 days for the previous HFM+AMO group, respectively. Overall, current preventive pharmacologic treatment use was low (15-16%; P>0.1 for current vs previous) in both groups. Previous HFM+AMO respondents reported better current acute treatment optimization. More respondents with current (80%) than previous HFM+AMO (66%) expressed concern with their current health (P<0.05). More than one-third of both groups wished their HCP better understood their mental/emotional health (current 37%, previous 35%; P>0.1 for current vs previous) and 47% (current) to 54% (previous) of respondents worried about asking their HCP too many questions (P>0.1 for current vs previous). CONCLUSION: Apart from optimization of acute medication, medical interventions did not significantly differentiate between the current and previous HFM+AMO groups. Use of preventive pharmacological medication was low in both groups. Adults with current HFM+AMO more often had health concerns, yet both groups expressed concerns of disease burden. Optimization of acute and preventive medication and addressing mental/emotional health concerns of patients are areas where migraine care may impact outcomes regardless of their disease burden.

Decision-making impairment under ambiguity but not under risk may underlie medication overuse in patients with chronic migraine.

OBJECTIVE: To explore whether patients with chronic migraine and medication overuse headache (CM + MOH) present with decision-making deficit. BACKGROUND: Factors underlying MOH in patients with CM remain unclear. Whether the process of decision-making plays a role in MOH is still controversial. Decision-making varies in the degree of uncertainty: under ambiguity where the probability of outcome is unknown, and under risk where probabilities are known. METHODS: Decisions under ambiguity and risk were assessed with the Iowa Gambling Task and the Cambridge Gambling Task, respectively, whereas executive function was assessed by the Wisconsin Card Sorting Test. RESULTS: A total of 75 participants: 25 patients with CM + MOH, 25 with CM, and 25 age- and sex-similar healthy controls (HCs), completed this cross-sectional study. There was no significant difference in headache profiles except for more frequent analgesic use (mean ± SD: 23.5 ± 7.6 vs. 6.8 ± 3.4 days; p < 0.001) and higher Severity of Dependence Scores (median [25th-75th percentile]: 8 [5-11] vs. 1 [0-4]; p < 0.001) in patients with CM + MOH compared to CM. Total net score (mean ± SD) on the Iowa Gambling Task in patients with CM + MOH, CM, and HCs were - 8.1 ± 28.7, 10.9 ± 29.6, and 14.2 ± 28.8, respectively. There was a significant difference between the three groups (F(2, 72) = 4.28, p = 0.017), with patients with CM + MOH making significantly more disadvantageous decisions than patients with CM (p = 0.024) and HCs (p = 0.008), while the CM and HC groups did not differ (p = 0.690). By contrast, there was no significant difference between the groups in the Cambridge Gambling Task and the Wisconsin Card Sorting Test. Furthermore, performance on the Iowa Gambling Task was inversely correlated with analgesic consumption (r = -0.41, p = 0.003), suggesting that decision-making under ambiguity may be related to MOH. CONCLUSIONS: Our data suggest that patients with CM + MOH had impaired decisions under ambiguous, but not risky situations. This dissociation indicates disrupted emotional feedback processing rather than executive dysfunction, which may underlie the pathogenesis of MOH.

Update of Gepants in the Treatment of Chronic Migraine.

PURPOSE OF REVIEW: Despite the unmet therapeutic needs of patients with chronic migraine (CM) and/or medication overuse, available treatment options are limited. Recently, four calcitonin gene-related peptide receptor antagonists, known as gepants, have been approved for the treatment of migraine. This review focuses on the preventive treatment of CM with gepants and highlights recent findings. RECENT FINDINGS: Two randomized controlled trials (RCTs) have shown promising results for rimegepant and atogepant as preventive treatments for CM. In an RCT targeting patients with CM, atogepant demonstrated a significant reduction in the mean monthly migraine days, irrespective of acute medication overuse. Moreover, the patients reported no significant safety concerns and exhibited good tolerance to treatment. These findings highlight the potential of gepants as a new and effective therapeutic option for patients with CM and/or medication overuse. Gepant use will help improve the management and quality of life of individuals with this debilitating condition.

Social cognition in chronic migraine with medication overuse: a cross-sectional study on different aspects of mentalization and social relationships.

BACKGROUND: Social cognition refers to all mental operations to decipher information needed in social interactions. Here we aimed to outline the socio-cognitive profile of Chronic Migraine with Medication Overuse (CM + MO), given they are recognized to be at risk of socio-cognitive difficulties. Given the multidimensionality of this construct, we considered: (1) socio-cognitive abilities, (2) socio-cognitive beliefs, (3) alexithymia and autism traits, and (4) social relationships. METHODS: Seventy-one patients suffering from CM + MO, 61 from episodic migraine (EM), and 80 healthy controls (HC) were assessed with a comprehensive battery: (1) the Faux Pas test (FP), the Strange Stories task (SS), the Reading Mind in the Eyes test (RMET), (2) the Tromsø Social Intelligence Scale, (3) the Toronto Alexithymia Scale, the Autism Spectrum Quotient, (4) the Lubben Social Network Scale, the Friendship Scale. RESULTS: CM + MO: (1) performed similar to EM but worse than HC in the FP and SS, while they were worse than EM and HC in the RMET; (2) were similar to EM and HC in social intelligence; (3) had more alexithymic/autistic traits than EM and HC; (4) reported higher levels of contact with their family members but felt little support from the people around them than HC. CONCLUSIONS: CM + MO results characterized by a profile of compromised socio-cognitive abilities that affects different dimensions. These findings may have a relevant role in multiple fields related to chronic headache: from the assessment to the management.

Validity of the Severity of Dependence Scale for detecting dependence behaviours in chronic migraine with medication overuse.

AIMS: In this study, we tested the validity of the Severity of Dependence Scale in detecting dependence behaviours in patients with chronic migraine and medication overuse (CM + MO) using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Leeds Dependence Questionnaire as gold standard measures. METHODS: Four hundred and fifty-four patients with CM + MO filled in the Severity of Dependence Scale and the Leeds Dependence Questionnaire and underwent a psychological evaluation for the diagnosis of substance dependence according to the DSM-IV criteria. RESULTS: Sixty-nine percent of subjects (n = 313) presented substance dependence according to the DSM-IV criteria. These patients scored significantly higher than those without substance dependence in Severity of Dependence Scale total score (Z = -3.29, p = 0.001), and in items 1 (Z = -2.44, p = 0.015), 2 (Z = -2.50, p = 0.012), 4 (Z = -2.05, p = 0.04), and 5 (Z = -3.39, p = 0.001). Severity of Dependence Scale total score (ß = 0.13, SE = 0.04, z = 3.49, p < 0.001) was a significant predictor for substance dependence. Receiver Operating Characteristic (ROC) curves showed that Severity of Dependence Scale discriminated patients with or without substance dependence. CONCLUSION: Severity of Dependence Scale could represent an interesting screening tool for dependency-like behaviors in CM + MO patients.

Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis.

BACKGROUND AND AIM: The pathogenesis of the pain that occurs in episodic migraine attack is due to the activation of the trigeminal system's first neuron receptors located on vessel wall. The release from the endothelium of nitric oxide, a product of arginine metabolism, causes vasodilation and stretching of the vascular trigeminal system and promotes pain. It is unknown whether this same metabolic event is involved in the pain accompanying chronic migraine. To understand the possible role of arginine in the pathogenesis of chronic migraine patients, we evaluated the metabolism of arginine in plasma of chronic migraine and control subjects. METHODS: We evaluated the metabolism of arginine in a group of patients affected by chronic migraine. Quantification of arginine, ornithine, citrulline, monomethyl arginine (NMMA), dimethylarginines (ADMA, SDMA), and tyramine was performed by ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometer. RESULTS: Chronic migraine patients showed low plasma levels of arginine, significantly elevated levels of ornithine, ADMA, and NMMA whereas the levels of citrulline and SDMA were in the range of controls. CONCLUSIONS: The elevated levels of ADMA and NMMA, inhibitors of nitric oxide synthase, suggest that the metabolism of arginine may be inhibited with a possible reduction of NO release in the circulation of chronic patients. This suggests that the origin of pain may not be related to the vasodilation of trigeminal vascular system that occurs in episodic migraine patients.

Management of chronic migraine with medication overuse by web-based behavioral program during the COVID-19 emergency: results at 12 months.

BACKGROUND: The study had been initiated because of restrictions put in place to control the spread of coronavirus in Milan in March 2020 that impacted clinical activities at our tertiary headache center in Milan (Foundation IRCSS Carlo Besta Neurological Institute). Treatment efforts were modified to make use of telephonic and internet communication to maintain care of our patients. METHODS: Nineteen patients had undergone our withdrawal protocol for medication overuse headache and were scheduled for follow-up that included pharmacological prophylaxis combined with behavioral therapy and mindfulness, generally performed in small group face-to-face sessions. A behavioral program was organized for them by technology modality (smartphone) due to the pandemic restrictions. RESULTS: The results concern 12-month follow-up. The clinical indexes showed migraine days per month 20.6 (± 6) pre vs 11.2 (± 3.1 at 12 months); medications intake per month 19.4 (± 5.8) pre vs 9.0 (± 4.6) at 12 months; MIDAS 67.7 (± 52.6) pre vs 71.1 (± 60) at 12 months; HIT-6 66.2 (± 5.3) pre vs 62.2 (± 5.9). CONCLUSION: The present study confirmed literature data, supporting the behavioral approach combined to traditional therapies as a novel method to follow patients and guarantee their benefit, also when applied using technology by telemedicine or smartphone.

CGRP Targeting Therapy for Chronic Migraine-Evidence from Clinical Trials and Real-world Studies.

PURPOSE OF REVIEW: Monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor have become part of the standard treatment for migraine in clinical practice. The current review focuses on the clinical evidence of CGRP monoclonal antibodies in patients with chronic migraine (CM), including more challenging cases. RECENT FINDINGS: CGRP monoclonal antibodies were more effective than placebo in reducing the number of monthly migraine days (MMDs), and the change relative to placebo in the treatment group was between - 1.2 and - 2.7 days at 3 months. CGRP monoclonal antibodies resulted in ≥ 50% response in 27.5 to 61.4% of patients, and doubled the odds for having ≥ 50% response. The findings were generally consistent in patients with coexisting medication overuse or with treatment failures to multiple preventive medications, including onabotulinumtoxinA. The results from real-world studies (RWS) were similar to those seen in clinical trials, and the changes from baseline in the number of MMDs and the response rates largely fell within the ranges of those reported in the treatment group in pivotal trials. The therapeutic effects typically started within a few days, and remained steady after regular treatment for up to 1 year. These agents were generally well tolerated, and the discontinuation rates due to adverse events in clinical trials and in many RWS were < 4.5%. CGRP monoclonal antibodies are effective and safe in the treatment of patients with CM, including clinical challenging cases. However, the role of CGRP monoclonal antibodies in a number of conditions, such as cardiovascular or cerebrovascular diseases, pregnancy, and overuse of opioids or barbiturates, needs to be further clarified.

The effect of emergency department pharmacists on drug overuse and drug underuse in patients with an ADE-related hospitalisation: a controlled intervention study.

BACKGROUND: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit. METHODS: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group. RESULTS: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039). CONCLUSION: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.

Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians.

DESCRIPTION: Antimicrobial overuse is a major health care issue that contributes to antibiotic resistance. Such overuse includes unnecessarily long durations of antibiotic therapy in patients with common bacterial infections, such as acute bronchitis with chronic obstructive pulmonary disease (COPD) exacerbation, community-acquired pneumonia (CAP), urinary tract infections (UTIs), and cellulitis. This article describes best practices for prescribing appropriate and short-duration antibiotic therapy for patients presenting with these infections. METHODS: The authors conducted a narrative literature review of published clinical guidelines, systematic reviews, and individual studies that addressed bronchitis with COPD exacerbations, CAP, UTIs, and cellulitis. This article is based on the best available evidence but was not a formal systematic review. Guidance was prioritized to the highest available level of synthesized evidence. BEST PRACTICE ADVICE 1: Clinicians should limit antibiotic treatment duration to 5 days when managing patients with COPD exacerbations and acute uncomplicated bronchitis who have clinical signs of a bacterial infection (presence of increased sputum purulence in addition to increased dyspnea, and/or increased sputum volume). BEST PRACTICE ADVICE 2: Clinicians should prescribe antibiotics for community-acquired pneumonia for a minimum of 5 days. Extension of therapy after 5 days of antibiotics should be guided by validated measures of clinical stability, which include resolution of vital sign abnormalities, ability to eat, and normal mentation. BEST PRACTICE ADVICE 3: In women with uncomplicated bacterial cystitis, clinicians should prescribe short-course antibiotics with either nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole (TMP-SMZ) for 3 days, or fosfomycin as a single dose. In men and women with uncomplicated pyelonephritis, clinicians should prescribe short-course therapy either with fluoroquinolones (5 to 7 days) or TMP-SMZ (14 days) based on antibiotic susceptibility. BEST PRACTICE ADVICE 4: In patients with nonpurulent cellulitis, clinicians should use a 5- to 6-day course of antibiotics active against streptococci, particularly for patients able to self-monitor and who have close follow-up with primary care.

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition.

BACKGROUND/AIM: Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse. METHODS: Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples. RESULTS: Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles. CONCLUSION: Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.

Persistent Opioid Use after Ophthalmic Surgery in Opioid-Naive Patients and Associated Risk Factors.

PURPOSE: To determine the rate and risk factors for new persistent opioid use after ophthalmic surgery in the United States. DESIGN: Retrospective claims-based cohort analysis. PARTICIPANTS: Opioid-naive patients 13 years of age and older who underwent incisional ophthalmic surgery between January 1, 2012, and June 30, 2017, and were included in Optum's de-identified Clinformatics Data Mart database. METHODS: New persistent opioid use was defined as filling an opioid prescription in the 90-day and the 91- to 180-day periods after the surgical procedure. The outcome variable was an initial perioperative opioid prescription fill. Rates of new persistent opioid use were calculated, and multivariate logistic regression models were used to identify variables increasing the risk of new persistent use and refill of an opioid prescription after the initial perioperative prescription in first 30 days. MAIN OUTCOME MEASURES: New persistent opioid use and refill. RESULTS: A total of 327 379 opioid-naive patients (mean age, 67 years [standard deviation, 16 years]; 178 067 women [54.4%]) who underwent ophthalmic surgery were examined. Among these patients, 14 841 (4.5%) had an initial perioperative opioid fill. The rate of new persistent opioid use was 3.4% (498 of 14 841 patients) compared with 0.6% (1833 of 312 538 patients) in patients who did not have an initial perioperative opioid fill. After adjusting for patient characteristics, initial perioperative opioid fill was associated independently with increased odds of new persistent use (adjusted odds ratio [OR], 6.21; 95% confidence interval [CI], 5.57-6.91; P < 0.001). Among patients who had filled an initial perioperative prescription, a prescription size of 150 morphine milligram equivalents or more was associated with an increased odds of refill (adjusted OR, 1.87; 95% CI, 1.58-2.22; P < 0.001). CONCLUSIONS: Exposure to opioids in the perioperative period is associated with new persistent use in patients who were previously opioid-naive. This suggests that exposure to opioids is an independent risk factor for persistent use in patients undergoing incisional ophthalmic surgery. Surgeons should be aware of those risks to identify at-risk patients given the current national opioid crisis and to minimize prescribing opioids when possible.

Prevalence of overuse of short-acting beta-2 agonists (SABA) and associated factors among patients with asthma in Germany.

BACKGROUND: Overuse of short-acting beta-2 agonists (SABA), which do not treat the underlying inflammation of asthma, is linked to poor clinical outcomes such as increased exacerbation risk. This study, as part of the SABINA program, estimated the prevalence of SABA overuse and associated variables in outpatients in Germany. METHODS: This retrospective study used anonymized electronic healthcare data from the Disease Analyzer database (IQVIA). A total of 15,640 patients aged ≥ 12 years with asthma who received ≥ 1 SABA prescription(s) between July 2017 and June 2018 in 924 general physician and 22 pneumologist (PN) practices were included. SABA overuse was defined as ≥ 3 prescribed inhalers (~ 200 puffs each) during the study period. The associations between SABA overuse and physician specialty, Global Initiative for Asthma (GINA) steps (based on asthma medications), age, sex, and inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) use were estimated using multivariable regression for patients with probable moderate (GINA step 2) and probable severe (GINA steps 3-5) asthma. RESULTS: Annually, 36% of all patients (GINA steps 1-5) in general and 38% in PN practices received ≥ 3 SABA inhalers. The risk of SABA overuse was 14% higher in patients treated by a general practitioner vs. a PN; 34% and 85% higher in GINA steps 4 and 5, respectively, vs. GINA step 3; and 40% higher in male vs. female patients. CONCLUSIONS: SABA overuse is prevalent among patients with asthma across all GINA steps in Germany, which may indicate suboptimal asthma control. Further studies are needed to investigate the reasons behind SABA overuse.

How does the brain change in chronic migraine? Developing disease biomarkers.

BACKGROUND: Validated chronic migraine biomarkers could improve diagnostic, prognostic, and predictive abilities for clinicians and researchers, as well as increase knowledge on migraine pathophysiology. OBJECTIVE: The objective of this narrative review is to summarise and interpret the published literature regarding the current state of development of chronic migraine biomarkers. FINDINGS: Data from functional and structural imaging, neurophysiological, and biochemical studies have been utilised towards the development of chronic migraine biomarkers. These biomarkers could contribute to chronic migraine classification/diagnosis, prognosticating patient outcomes, predicting response to treatment, and measuring treatment responses early after initiation. Results show promise for using measures of brain structure and function, evoked potentials, and sensory neuropeptide concentrations for the development of chronic migraine biomarkers, yet further optimisation and validation are still required. CONCLUSIONS: Imaging, neurophysiological, and biochemical changes that occur with the progression from episodic to chronic migraine could be utilised for developing chronic migraine biomarkers that might assist with diagnosis, prognosticating individual patient outcomes, and predicting responses to migraine therapies. Ultimately, validated biomarkers could move us closer to being able to practice precision medicine in the field and thus improve patient care.

Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine.

INTRODUCTION: Acute medication overuse is prevalent in patients with migraine. METHODS: In three phase 3, double-blind, randomized, placebo-controlled studies, patients with episodic migraine (EVOLVE-1 and EVOLVE-2) or chronic migraine (REGAIN) were randomized 2:1:1 to monthly subcutaneous injections of placebo or galcanezumab 120 or 240 mg for 3 or 6 months. This subgroup analysis evaluated mean changes in the number of monthly migraine headache days in each treatment among patients with versus without baseline acute medication overuse via mixing modelling with repeated measures. RESULTS: The percentages of patients with baseline medication overuse in placebo, galcanezumab 120-mg and 240-mg groups, respectively, were 19.4%, 17.3%, and 19.3% for EVOLVE-1/-2 (pooled; post hoc), and 63.4%, 64.3%, and 64.1% for REGAIN (a priori). Both galcanezumab doses demonstrated significant improvement compared with placebo for overall least squares mean change in monthly migraine headache days in patients with baseline medication overuse in both the episodic and chronic migraine studies (p ≤ 0.001). Furthermore, both galcanezumab doses reduced average monthly medication overuse rates compared to placebo (p < 0.001) in both patient populations with medication overuse at baseline. CONCLUSIONS: Galcanezumab appears to be effective for the preventive treatment of episodic and chronic migraine in patients who overuse acute medications.Trial registration: ClinicalTrials.gov Identifiers: NCT02614183, NCT02614196, and NCT02614261.

Secondary headache attributed to exposure to or overuse of a substance.

BACKGROUND: Secondary headaches attributed to exposure to or the overuse of a substance are classified under chapter eight in the International Classification of Headache Disorders 3rd edition. Three distinct sub-chapters consider: 1. Headache attributed to exposure to a substance, 2. Medication overuse headache, and 3. Headache attributed to substance withdrawal. Headache attributed to exposure to a substance refers to a headache with onset immediately or within hours after the exposure, while medication overuse headache is a headache occurring on 15 or more days per month that has developed as a consequence of regular usage of acute headache medication(s) for more than three consecutive months in a patient with a pre-existing primary headache disorder. The withdrawal of caffeine, oestrogen, and opioids is most often associated with the development of headache. DISCUSSION: Despite the current headache classification, there is no certainty of a causal relationship between the use of any substance and the development of headache. Some substances are likely to provoke headache in patients that suffer from a primary headache disorder like migraine, tension-type headache or cluster headache, while others were described to cause headache even in people that generally do not get headaches. Toxic agents, such as carbon monoxide (CO) are difficult to investigate systematically, while other substances such as nitric oxide (NO) were specifically used to induce headache experimentally. If a patient with an underlying primary headache disorder develops a headache, in temporal relation to exposure to a substance, which is significantly worse than the usual headache it is considered secondary. This is even more the case if the headache phenotype is different from the usually experienced headache characteristics. Medication overuse headache is a well-described, distinct disease entity with only marginally understood pathophysiology and associated psychological factors. Managing medication overuse headache patients includes education, detoxification, prophylactic treatments and treating comorbidities, which is reflected in available guidelines. Viewing medication overuse headache as a separate entity helps clinicians and researchers better recognise, treat and study the disorder. CONCLUSION: Identification of substances that may cause or trigger secondary headache is important in order to educate patients and health care professionals about potential effects of these substances and prevent unnecessary suffering, as well as deterioration in quality of life. Treatment in case of medication overuse and other chronic headache should be decisive and effective.

Determinants of pain interference and headache impact in patients who have chronic migraine with medication overuse: Results from the MOTS trial.

OBJECTIVE: "Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. METHODS: Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model. RESULTS: PROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact. CONCLUSIONS: Chronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.