Medication overuse headache in patients with chronic migraine using cannabis: A case-referent study.

OBJECTIVE: To examine whether cannabis use predicts medication overuse headache (MOH) in patients with chronic migraine (CM). METHODS: Electronic chart review was conducted by combining the terms "CM," "medication overuse," "cannabis," "cannabidiol," and "tetrahydrocannabinol" for patients seen at our headache clinics from 2015 to 2019. Of 729 charts consecutively screened, 368 met our inclusion criteria, that is, adult patients with CM with ≥1-year CM duration. The following variables were extracted from the included patient charts: MOH diagnosis, age, sex, migraine frequency, current CM duration, current cannabis use duration, overused acute migraine medications, current MOH duration, and types of cannabis products used. Logistic regression was used to identify variables predicting MOH while controlling for remaining predictors. Agglomerative hierarchical clustering (AHC) was conducted to explore natural clusters using all predictor variables. RESULTS: There were 212 patients with CM and MOH (cases; median age 43 years, interquartile range [IQR] 33-54; 177 [83%] females) and 156 patients with CM without MOH (referents; median age 40 years, IQR 31-49; 130 [83%] females). MOH was present in 81% (122/150) of current cannabis users compared with 41% (90/218) in those without cannabis use-adjusted odds ratio 6.3 (95% CI: 3.56 to 11.1, p < 0.0001). Current cannabis use was significantly associated with opioid use (Spearman's rho 0.26, p < 0.0001). Both current cannabis use (rho 0.40, p < 0.0001) and opioid use (rho 0.36, p < 0.0001) were significantly associated with MOH. Similarly, AHC revealed two major natural clusters. Cluster I patients featured 9.3 times higher current cannabis use, 9.2 times higher current opioid use, and 1.8 times higher MOH burden than those in Cluster II (p < 0.0001). CONCLUSION: Cannabis use was significantly associated with increased prevalence of MOH in CM. Bidirectional cannabis-opioid association was observed-use of one was associated with use of the other. Advising patients with CM and MOH to reduce cannabis use may help treat MOH effectively.

[A Study of Outcome Measures and Establishment of Benchmarks for Antimicrobial Stewardship Programs].

Over the past few decades, the effectiveness of antibiotics has been diminished owing to the emergence of antimicrobial resistance resulting from the overuse of antibiotics. Antimicrobial stewardship aims to improve the appropriateness of antibiotic use to reduce antimicrobial resistance and benefit patients. Antimicrobial stewardship requires structural prerequisites for implementing antimicrobial stewardship programs (ASPs), such as the presence of a multidisciplinary antimicrobial stewardship team (AST), to ensure appropriate antimicrobial use at healthcare facilities. However, manpower shortage for ASTs in most Japanese hospitals has resulted in limited implementation of ASPs. Our study provided a directive for promotion of comprehensive ASPs including various outcome measures. Our findings would provide useful benchmarks for hospitals planning to implement ASPs in Japan as well as around the world. This review provides a framework for evaluating the outcome measures and benchmarks of ASPs based on our study.

Headache management in a Veteran population: First considerations.

It is estimated that almost half the general population has a headache disorder. The majority of these are considered tension-type headaches. Migraines and chronic daily headache (CDH) are not as common but are much more debilitating. Although CDH/chronic migraine (CM) occurs in about 3% of the population, it has been found to be 20% or higher in the post 9/11 combat Veteran population. Data from the Veterans Health Administration show that more than 380,000 Veterans, younger than 50 years, received care for a headache in 2017. Approximately 75% of the headache care was from a primary care provider. The purpose of the article is to review physical examination for the veteran with a history of a headache disorder, discuss contributing factors and comorbid conditions, as well as give an overview of current treatment options, with a focus on the post-9/11 combat Veteran who has CDH/CM.

Metagenomic study focusing on antibiotic resistance genes from the sediments of River Yamuna.

Antibiotic resistance is one of the major health concerns of the present century. The direct discharge of urban sewage, hospital effluents, and pharmaceutical wastes increases the concentration of antibiotics in riverine ecosystems. This provides selection pressure for the development of novel antibiotic-resistant strains. In this study, metagenomics approach was employed a for constructing a comprehensive profile of the Antibiotic Resistance Genes (ARGs) identified in the sediments of the Yamuna River. A total of 139 ARGs were identified from 39 microbial species. Abundance analysis revealed that, aminoglycoside, beta-lactam, macrolide, and tetracycline resistance genes were highly abundant in the sediment samples obtained from the Yamuna River. The evolutionary relationships among the ARGs were studied by phylogenetic analyses, which revealed that, the identified resistome comprised eight clusters. Network analysis was performed for investigating the broad-spectrum profiles of the ARGs and their enrichment in different biological functions and pathways. Protein-protein interaction (PPI) analyses revealed that, 76, 36, 18, and 5 Gene Ontology (GO)-terms were significantly enriched in Biological process, Molecular Function, Cellular Component, and KEGG Pathways analysis, respectively. The present study elucidates the ecology of microbial antibiotic resistance in the riverine ecosystem of the Yamuna River and provides novel insights into the environmental hotspots that are amenable to the emergence of ARGs in the contaminated riverine hydrosphere.

Acupuncture in the Management of Medication Overuse and Drug-induced Aseptic Meningitis Headache: A Case Report.

Headache disorders are burdensome, both in terms of the number of people they affect, and in terms of associated healthcare spending. This report presents a 36-year-old female admitted to a tertiary university hospital with a primary complaint of intractable headache, caused by a combination of medication overuse headache, and headache secondary to aseptic meningitis. During her hospital stay, opioid analgesic doses were initially increased without success in an attempt to control her headache. Despite multiple medication trials the patient's headache failed to improve. On day ten of her hospitalization, she underwent a thirty-minute acupuncture session which resulted in immediate relief of her headache. She received one more acupuncture treatment the following day and was discharged to an acute inpatient rehabilitation facility on a vastly reduced dose of opioids. Instructions on how to taper the remaining opioids were provided, and the patient was scheduled for outpatient acupuncture therapy sessions for further headache management. This report demonstrates the importance of recognizing acupuncture as a viable treatment option for medication overuse headache and for headache secondary to systemic diseases such as aseptic meningitis. Furthermore, acupuncture should also be considered as a nonpharmacological modality to be used when tapering a patient off of high doses of opioids.

HLA class I alleles are associated with clinic-based migraine and increased risks of chronic migraine and medication overuse.

OBJECTIVE: We aimed to evaluate associations of human leukocyte antigen variants with migraine or headache in hospital and population-based settings. METHODS: The case-control study population, aged 30-70, included 605 clinic-based migraine patients in a medical center and 8449 population-based participants in Taiwan Biobank (TWB). Clinic-based cases were ascertained by neurologists. Participants in Taiwan Biobank were interviewed by a structured questionnaire including headache and migraine history; among them, 2394 had headache or migraine history while 6055 were free of headache and served as controls. All subjects were genotyped by Axiom Genome-Wide Single Nucleotide Polymorphism Arrays and imputed for eight classical human leukocyte antigen genes. Human leukocyte antigen frequencies were compared between clinic-based and self-reported patients and controls. We utilized likelihood ratio tests to examine human leukocyte antigen-disease associations and logistic regressions to estimate the effect of human leukocyte antigen alleles on migraine. RESULTS: Human leukocyte antigen-B and C showed significant associations with clinic-based migraine (q-value < 0.05). Human leukocyte antigen-B*39:01, human leukocyte antigen-B*51:01, human leukocyte antigen-B*58:01 and human leukocyte antigen-C*03:02 were significantly associated with migraine, with age and sex-adjusted odds ratios (95% CIs) of 1.80 (1.28-2.53), 1.50 (1.15-1.97), 1.36 (1.14-1.62) and 1.36 (1.14-1.62), correspondingly. Clinic-based migraineurs carrying human leukocyte antigen-B*58:01 or human leukocyte antigen-C*03:02 had 1.63 (1.11-2.39) -fold likelihood to have chronic migraine with medication-overuse headache compared to episodic migraine. However, no human leukocyte antigen genes were associated with self-reported headache or migraine in the community. CONCLUSIONS: Human leukocyte antigen class I genetic variants are positively associated with risk of clinic-based migraine but not self-reported migraine or headache and may contribute to migraine chronification and medication overuse.

Maladaptive activation of Nav1.9 channels by nitric oxide causes triptan-induced medication overuse headache.

Medication-overuse headaches (MOH) occur with both over-the-counter and pain-relief medicines, including paracetamol, opioids and combination analgesics. The mechanisms that lead to MOH are still uncertain. Here, we show that abnormal activation of Nav1.9 channels by Nitric Oxide (NO) is responsible for MOH induced by triptan migraine medicine. Deletion of the Scn11a gene in MOH mice abrogates NO-mediated symptoms, including cephalic and extracephalic allodynia, photophobia and phonophobia. NO strongly activates Nav1.9 in dural afferent neurons from MOH but not normal mice. Abnormal activation of Nav1.9 triggers CGRP secretion, causing artery dilatation and degranulation of mast cells. In turn, released mast cell mediators potentiates Nav1.9 in meningeal nociceptors, exacerbating inflammation and pain signal. Analysis of signaling networks indicates that PKA is downregulated in trigeminal neurons from MOH mice, relieving its inhibitory action on NO-Nav1.9 coupling. Thus, anomalous activation of Nav1.9 channels by NO, as a result of chronic medication, promotes MOH.

Restrictive measure for the commercialization of antimicrobials in Brazil: results achieved.

OBJECTIVE: To assess whether the incidence of hospital infection by a resistant microorganism decreased after the implementation of the restrictive measure of the National Health Surveillance Agency for the commercialization of antimicrobials. METHODS: A historical cohort study of medical records of adult patients admitted to a general and public hospital from May 2010 to July 2011. A cohort was formed with patients admitted in the period before the restrictive measure for the commercialization of antimicrobials (Phase I) and a second cohort was formed with patients admitted after the implementation of the restrictive measure (Phase II). RESULTS: The instantaneous risk of hospital infection by a resistant microorganism was estimated at seven by 1,000 people-time (95%CI 0.006-0.008) in Phase I, and four by 1,000 people-time (95%CI 0.003-0.005) in Phase II of the study. The differences between the survival curves in the different phases of the study and stratified by age group were also significant (p < 0.05). CONCLUSIONS: The results suggest that the implementation of the restrictive measure of the commercialization of antimicrobials by the National Health Surveillance Agency reduced the incidence of hospital infection by a resistant microorganism.

Rates of New Persistent Opioid Use After Vaginal or Cesarean Birth Among US Women.

Importance: Research has shown an association between opioid prescribing after major or minor procedures and new persistent opioid use. However, the association of opioid prescribing with persistent use among women after vaginal delivery or cesarean delivery is less clear. Objective: To assess the association between opioid prescribing administered for vaginal or cesarean delivery and rates of new persistent opioid use among women. Design, Setting, and Participants: This retrospective cohort study used national insurance claims data for 988 036 women from a single private payer from January 1, 2008, to December 31, 2016. Participants included reproductive age, opioid-naive women with 1 year of continuous enrollment before and after delivery. For participants with multiple births, only the first birth was included. Exposures: Peripartum opioid prescription (1 week before delivery to 3 days after discharge) captured by pharmacy claims, including prescription timing and size in oral morphine equivalents. Multivariable adjusted odds ratios were estimated using regression models. Main Outcomes and Measures: Rates of new persistent opioid use, defined as pharmacy claims for 1 or more opioid prescription 4 to 90 days after discharge and 1 or more prescription 91 to 365 days after discharge among women who filled peripartum opioid prescriptions. Results: In total, 308 226 deliveries were included: 195 013 (63.3%) vaginal deliveries and 113 213 (36.7%) cesarean deliveries. Participant mean (SD) age was 31.3 (5.3) years, and 70 567 (51.0%) were white patients. Peripartum opioid prescriptions were filled by 27.0% of women with vaginal deliveries and 75.7% of women with cesarean deliveries. Among them, 1.7% of those with vaginal deliveries and 2.2% with cesarean deliveries had new persistent opioid use. By contrast, among women not receiving a peripartum opioid prescription, 0.5% with vaginal delivery and 1.0% with cesarean delivery had new persistent opioid use. From 2008 to 2016, opioid prescription fills decreased for vaginal deliveries from 26.9% to 23.8% (P < .001) and for cesarean deliveries from 75.5% to 72.6% (P < .001), and fewer women had new persistent use (vaginal delivery, from 2.2% to 1.1%; P < .001; cesarean delivery, from 2.5% to 1.3%; P < .001). The strongest modifiable factor associated with new persistent opioid use after delivery was filling an opioid prescription before delivery (adjusted odds ratio, 1.40; 95% CI, 1.05-1.87). For vaginal deliveries, receiving a prescription equal to or more than 225 oral morphine equivalents was associated with new persistent opioid use (adjusted odds ratio, 1.25; 95% CI, 1.06-1.48). Women who underwent cesarean delivery and had a hysterectomy were more likely to develop persistence (AOR, 2.75; 95% CI, 1.33-5.70), although women who underwent a nonelective (AOR, 0.97; 95% CI, 0.88-1.07) or repeat cesarean (AOR, 1.45; 95% CI, 0.93-2.28) were not more likely. For cesarean deliveries, risk factors were associated with patient attributes such as tobacco use (adjusted odds ratio, 1.82; 95% CI, 1.56-2.11), psychiatric diagnoses, history of substance use (adjusted odds ratio, 1.43; 95% CI, 1.10-1.86), and pain conditions. Conclusions and Relevance: The results of the present study suggested that opioid prescribing and new persistent use after vaginal delivery or cesarean delivery have decreased since 2008. However, modifiable prescribing patterns were associated with persistent opioid use for patients who underwent vaginal delivery, and risk factors following cesarean delivery mirrored those of other surgical conditions. Judicious opioid prescribing and preoperative risk screening may be opportunities to decrease new persistent opioid use after childbirth.

Medication Overuse and Medication Overuse Headache: Risk Factors, Comorbidities, Associated Burdens and Nonpharmacologic and Pharmacologic Treatment Approaches.

PURPOSE OF REVIEW: With a worldwide high disease burden, medication overuse headache (MOH) is an endemic and disabling neurological disorder. Because of the limitations of previous study designs, there are still debates and questions regarding the disease's nature and treatment strategy. This review will discuss the following concepts; (1) recent progress in association between medication overuse (MO) and MOH; (2) the burden, risk factors and comorbidities of MOH; (3) evidence of treatment in patients with MOH. RECENT FINDINGS: The causal relationship between MO and MOH has not been identified. Currently, the treatment policy is still mainly based on small clinical observations, some with highly specified patients. In addition to withdrawal and preventive treatment, some studies have provided evidence for nonpharmacological treatments. Well-designed studies for specific treatment strategies with enough statistical power are warranted to make more relevant, better clinical decisions.

Restrictive measure for the commercialization of antimicrobials in Brazil: results achieved / Medida restritiva para comercialização de antimicrobianos no Brasil: resultados alcançados

ABSTRACT OBJECTIVE To assess whether the incidence of hospital infection by a resistant microorganism decreased after the implementation of the restrictive measure of the National Health Surveillance Agency for the commercialization of antimicrobials. METHODS A historical cohort study of medical records of adult patients admitted to a general and public hospital from May 2010 to July 2011. A cohort was formed with patients admitted in the period before the restrictive measure for the commercialization of antimicrobials (Phase I) and a second cohort was formed with patients admitted after the implementation of the restrictive measure (Phase II). RESULTS The instantaneous risk of hospital infection by a resistant microorganism was estimated at seven by 1,000 people-time (95%CI 0.006-0.008) in Phase I, and four by 1,000 people-time (95%CI 0.003-0.005) in Phase II of the study. The differences between the survival curves in the different phases of the study and stratified by age group were also significant (p < 0.05). CONCLUSIONS The results suggest that the implementation of the restrictive measure of the commercialization of antimicrobials by the National Health Surveillance Agency reduced the incidence of hospital infection by a resistant microorganism.

RESUMO OBJETIVO Avaliar se a incidência de infecção hospitalar por microrganismo resistente diminuiu após a implementação da medida restritiva da Agência Nacional de Vigilância Sanitária para comercialização de antimicrobianos. MÉTODOS Estudo de coorte histórica de registros de prontuários de pacientes adultos admitidos para internação em um hospital geral e público no período de maio de 2010 a julho de 2011. Foi formada uma coorte com pacientes internados em período anterior à medida restritiva para comercialização de antimicrobianos (Fase I) e uma segunda coorte com pacientes admitidos após a implantação da medida restritiva (Fase II). RESULTADOS O risco instantâneo de infecção hospitalar por microrganismo resistente foi estimado em sete por 1.000 pessoas-tempo (IC95% 0,006-0,008) na Fase I, e quatro por 1.000 pessoas-tempo (IC95% 0,003-0,005) na Fase II do estudo. As diferenças entre as curvas de sobrevida nas diferentes fases do estudo e estratificadas pela faixa etária também foram significativas (p < 0,05). CONCLUSÕES Os resultados sugerem que a implantação da medida restritiva de comercialização de antimicrobianos pela Agência Nacional de Vigilância Sanitária reduziu a incidência de infecção hospitalar por microrganismo resistente.