Targeting the endocannabinoid system for the management of low back pain.

Low back pain (LBP) is a major unmet clinical need. The endocannabinoid system (ECS) has emerged as a promising therapeutic target for pain, including LBP. This review examines the evidence for the ECS as a therapeutic target for LBP. While preclinical studies demonstrate the potential of the ECS as a viable therapeutic target, clinical trials have presented conflicting findings. This review underscores the need for innovative LBP treatments and biomarkers and proposes the ECS as a promising avenue for their exploration. A deeper mechanistic understanding of the ECS in LBP could inform the development of new pain management strategies.

Safety, tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractory chronic migraine with cardiovascular risk factors: A retrospective study.

BACKGROUND: Dihydroergotamine (DHE), like triptans, is contraindicated in patients with ischemic heart disease or coronary vasospasm. Its true safety, tolerability, and efficacy in patients with cardiovascular risk without ischemic heart disease or coronary vasospasm remain unclear. OBJECTIVES: To assess the safety, tolerability, and effectiveness of repetitive intravenous DHE in patients with cardiovascular risk factors. METHODS: A single-center, retrospective cohort study was conducted at the Jefferson Headache Center inpatient unit for refractory chronic migraine patients treated with our intravenous DHE protocol between January 1, 2019, and October 15, 2019. We evaluated tolerability and effectiveness outcomes based on atherosclerotic cardiovascular disease 10-year calculated risk scores, stratified into low (<5.0%) and elevated (≥5.0%) risk. Data were presented in mean ± standard deviation or median (25th percentile, 75th percentile) if non-normally distributed. RESULTS: Among 347 patients (median age of 46 [36, 57], female n = 278 [80.1%]), who received inpatient intravenous DHE, 227 patients (age 53 [45, 60], female 81.1%) had calculable risk scores, 64 (28.2%) had elevated risk, and 38 (16.7%) had cardiology consultations. There were no clinically significant electrocardiogram abnormalities or cardiovascular adverse events. The median hospital length of stay was 6 (5, 7) days. Compared to the low-risk group, those with elevated risk had higher nausea (31.3% vs. 14.1%, p = 0.008), but similar initial DHE dose (0.5 [0.25, 0.5] vs. 0.5 [0.25, 0.5], p = 0.009), lower final DHE dose (0.75 [0.5, 1] vs. 1 [0.75, 1] p < 0.001), and lower pain reduction after admission (-3.8 [2.1, 6] vs. -5 [3, 7] p = 0.037). CONCLUSION: Patients receiving intravenous DHE by the Jefferson Headache Center inpatient headache protocol had significantly reduced pain severity at discharge. No clinically significant cardiac or electrocardiogram abnormalities were detected in patients with elevated (or low) atherosclerotic cardiovascular disease risk. Repetitive intravenous DHE used by our protocol was safe in refractory chronic migraine patients.

Intravenous ibuprofen for acute treatment of migraine: A double-blind, randomized, placebo-controlled pilot study.

OBJECTIVE: To evaluate the efficacy and safety of intravenous (IV) Ibuprofen for acute treatment of migraine. BACKGROUND: IV nonsteroidal anti-inflammatory drugs (NSAIDs) are an alternative to oral NSAIDs, especially in patients with severe migraine who have emesis or gastroparesis. To date, only three IV NSAIDs (ketorolac, ibuprofen, and meloxicam) are available in the United States for use in moderate and severe pain, but no placebo-controlled trial is available for migraine. We performed a single-center, double-blind, randomized, placebo-controlled pilot study to evaluate the efficacy and safety of IV ibuprofen as an acute treatment of migraine (NCT01230411). METHODS: Individuals with episodic migraine were screened at the Jefferson Headache Center. Qualified subjects were treated for migraine attacks within 2-72 h following the headache onset with either 800 mg of IV ibuprofen or placebo in 250 ml saline bolus. Migraine pain intensity (4-point Likert scale) and associated symptoms were assessed at predetermined time points (0.25, 0.5, 1, 1.5, 2, 4, 8, 24 h). The primary endpoint was pain relief at 2 h after infusion. Important secondary endpoints included pain freedom at 2 h, sustained relief over 24 h, use of rescue therapy, and absence of associated symptoms. Adverse events (AEs) were also collected. RESULTS: Seventy-four participants were enrolled between 2011 and 2017. Forty-four subjects (female 33/44; 75.0%) with mean (SD) age 41.0 (11.2)   11.2 years came for the treatment. All treated subjects (n = 44) were included in the analysis. Among them, 23 were randomized to receive IV ibuprofen. Both groups were demographically similar except for longer migraine duration (i.e., years lived with disease) in the active treatment than in the placebo group. At 2 h posttreatment, pain relief was found in 74% (17/23) and 48% (10/21) after IV ibuprofen and placebo, respectively (odds ratio [OR] 3.12, 95% CI: 0.88-11.0; p = 0.078). Other secondary endpoints at 2 and 24 h were not significant. The longitudinal repeated-measures analysis within 2 h on ibuprofen treatment showed significant pain relief (OR 2.47, 95% CI 1.08-5.7; p = 0.033) and absence of associated symptoms: photophobia (OR 4.0, 95% CI 1.57-10.3; p = 0.004), phonophobia (OR 3.12, 95% CI 1.16-8.4; p = 0.025), and osmophobia (OR 3.45, 95% CI 1.01-11.8; p = 0.048). AEs were observed in seven subjects in both groups, with arm pain being the most common. No serious AE was reported. CONCLUSION: This study did not meet the primary endpoint but showed pain relief and elimination of several associated symptoms within 2 h on repeated-measures analysis. Although limited by small sample size and high placebo response, our results indicate that IV ibuprofen may be a safe and effective option for acute treatment of migraine, but more extensive studies are necessary.

Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.

ABSTRACT: We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.

Understanding surgical education needs in Zambian residency programs from a Resident's perspective.

INTRODUCTION: Approximately 100 surgeons in Zambia serve a population of 16 million, a severe shortage in basic surgical care. Surgical education in Zambia and other low-middle income countries has not been well characterized. The aim of this study was to evaluate surgical training resources from a resident perspective. METHODS: 6 of 8 COSECSA-accredited major medical centers were included. We developed a Surgical Education Capacity Tool to evaluate hospital characteristics including infrastructure, education, and research. The questionnaire was completed by administrators and trainees. RESULTS: 18 of 45 trainees were surveyed. Caseloads and faculty-to-trainee ratio varied by location. No sites had surgical skills, simulation, or research labs. Most had medical libraries, lecture halls, and internet. Outpatient clinics, bedside teaching, M&M conferences, and senior supervision were widely available. Despite some exposure, research mentorship, basic science, and grant application guidance were critically limited. CONCLUSIONS: Lack of access to proper infrastructure, research, and personnel all impact surgical training and education. The Surgical Education Capacity Tool offers insights into areas of potential improvement, and is applicable to other LMICs.

Substance Use, Demographic and Socioeconomic Factors Are Independently Associated With Postpartum HIV Care Engagement in the Southern United States, 1999-2016.

BACKGROUND: Retention in care (RIC) and viral suppression (VS) are associated with reduced HIV transmission and mortality. Studies addressing postpartum engagement in HIV care have been limited by small sample size, short follow-up, and a lack of data from the Southeast United States. METHODS: HIV-positive adult women with ≥1 prenatal visit at the Vanderbilt Obstetrics Comprehensive Care Clinic from 1999 to 2015 were included. Poor RIC was defined as not having ≥2 encounters per year, ≥90 days apart; poor VS was a viral load >200 copies/mL. Modified Poisson regression was used to estimate adjusted relative risks (aRRs) of poor postpartum RIC and VS. RESULTS: Among 248 women over 2070 person-years of follow-up, 37.6% person-years had poor RIC and 50.4% lacked VS. Prenatal substance use was independently associated with poor RIC (aRR, 1.40; 95% confidence interval [CI], 1.08-1.80) and poor VS (aRR, 1.20; 95% CI, 1.04-1.38), and lack of VS at enrollment was associated with poor RIC (aRR, 1.64; 95% CI, 1.15-2.35) and poor VS (aRR, 1.59; 95% CI, 1.30-1.94). Hispanic women were less likely and women with lower educational attainment were more likely to have poor RIC. Women >30 years of age and married women were less likely to have poor VS. CONCLUSIONS: In this population of women in prenatal care at an HIV primary medical home in Tennessee, women with prenatal substance use and a lack of VS at enrollment into prenatal care were at greater risk of poor RIC and lack of VS postpartum. Interventions aimed at improving postpartum engagement in HIV care among these high-risk groups are needed.

Surgical registrars' perceptions of surgical training and capacity in Zambia: Results from three COSECSA affiliated training hospitals.

BACKGROUND: Surgery is a vital component of a comprehensive health system, but there are often personnel limitations in resource constrained areas. Zambia provides post graduate surgical training through two systems to help address this shortage. However, no studies have analyzed surgical trainees' perceptions of these programs. METHODS: Surgical registrars at COSECSA affiliated hospitals in Zambia were surveyed about their programs. Responses were analyzed to identify key strengths and challenges across several categories including: operative training, clinical training, educational experiences, and career plans. RESULTS: Registrars report having significant independence and receiving broad and high quality operative training. They note specific challenges including limitations in specialty training, resources, and infrastructure. CONCLUSIONS: Zambian training programs have the potential to increase number of surgeons in Zambia by a significant amount in the coming years. These programs have many strengths but also face challenges in their goal to expand surgical access in the country.

Typhoid Fever and Acute Appendicitis: A Rare Association Not Yet Fully Formed.

Infections caused by foodborne enteric pathogens including typhoidal and non-typhoidal Salmonella species can mimic symptoms of acute appendicitis. The association between such bacterial pathogens and pathology-proven acute appendicitis has been described, but this link is poorly understood. Here we describe a case of a young man with typhoid fever presenting with histology-proven acute appendicitis requiring urgent appendectomy, and provide a brief review of relevant literature to prompt more widespread recognition of this rare cause of a common surgical emergency.

Teaching global health with simulations and case discussions in a medical student selective.

BACKGROUND: Among US medical schools, demand for Global Health (GH) programs continues to grow. At the same time, cultural competency training has become a priority for medical students who will care for an increasingly diverse US patient population. We describe a pilot period for a new GH Selective designed to introduce medical students to global medicine and enhance culturally-sensitive communication skills. METHODS: As a 4-week clinical clerkship, the GH Selective was offered annually over a three-year period to a total of 33 students. Activities included clinical assignments, cultural competency and clinical skills simulations, patient case discussions in tropical medicine, journal clubs, and lectures. Faculty assessments of student performance and student evaluations of course content were focused on 6 course objectives, adapted from standardized GH objectives. RESULTS: For each offering of the GH Selective, at least 40 faculty members and fellows volunteered over 200 teaching hours from 11 medical school departments. Student feedback was consistently positive through competency-based curricular evaluations. As a result of its successes, the course is now offered on a biannual basis. DISCUSSION: Experiential, student-centered teaching employed in this course proved successful as an introduction to delivery of evidence-based and culturally sensitive GH. Special emphasis on working with standardized patients in interdisciplinary and cross-cultural simulations provided students with clinical skills applicable for care provided both locally and on international rotations. CONCLUSION: With a special emphasis on cross-cultural sensitivity, this pilot elective trained future practitioners in fund of knowledge, clinical skills, and service delivery methods in GH.

Twelve tips for improving the effectiveness of web-based multimedia instruction for clinical learners.

Using educational technology does not necessarily make medical education more effective. There are many different kinds of technology available to the contemporary medical teacher and what constitutes effective use may depend on the technology, the learning situation and many other factors. Web-based multimedia instruction (WBMI) provides learners with self-directed independent learning opportunities based on didactic material enhanced with multimedia features such as video and animations. WBMI may be used to replace other didactic events (e.g. lectures) or it may be provided in addition to other learning opportunities. Clinical educators looking to use WBMI need to make sure that it will meet both their learners' needs and the program's needs, and it has to align to the contexts in which it is used. The following 12 tips have been developed to help guide faculty through some of the key features of the effective use of WBMI in clinical teaching programs. These tips are based on more than a decade developing, using and appraising WBMI in support of surgical clerkship education across the USA and beyond and they are intended both to inform individual uses of WBMI in clinical training and to guide the strategic use of WBMI in clinical clerkship curricula.

WISE-MD usage among millennial medical students.

BACKGROUND: E-learning is increasingly common in undergraduate medical education. Internet-based multimedia materials should be designed with millennial learner utilization preferences in mind for maximal impact. METHODS: Medical students used all 20 Web Initiative for Surgical Education of Medical Doctors modules from July 1, 2013 to October 1, 2013. Data were analyzed for topic frequency, time and week day, and access to questions. RESULTS: Three thousand five hundred eighty-seven students completed 35,848 modules. Students accessed modules for average of 51 minutes. Most frequent use occurred on Sunday (23.1%), Saturday (15.4%), and Monday (14.3%). Friday had the least use (8.2%). A predominance of students accessed the modules between 7 and 10 PM (34.4%). About 80.4% of students accessed questions for at least one module. They completed an average of 40 ± 30 of the questions. Only 827 students (2.3%) repeated the questions. CONCLUSIONS: Web Initiative for Surgical Education of Medical Doctors has peak usage during the weekend and evenings. Most frequently used modules reflect core surgical problems. Multiple factors influence the manner module questions are accessed.

Medical students as human subjects in educational research.

INTRODUCTION: Special concerns often arise when medical students are themselves the subjects of education research. A recently completed large, multi-center randomized controlled trial of computer-assisted learning modules for surgical clerks provided the opportunity to explore the perceived level of risk of studies where medical students serve as human subjects by reporting on: 1) the response of Institutional Review Boards (IRBs) at seven institutions to the same study protocol; and 2) the thoughts and feelings of students across study sites about being research subjects. METHODS: From July 2009 to August 2010, all third-year medical students at seven collaborating institutions were eligible to participate. Patterns of IRB review of the same protocol were compared. Participation burden was calculated in terms of the time spent interacting with the modules. Focus groups were conducted with medical students at each site. Transcripts were coded by three independent reviewers and analyzed using Atlas.ti. RESULTS: The IRBs at the seven participating institutions granted full (n=1), expedited (n=4), or exempt (n=2) review of the WISE Trial protocol. 995 (73% of those eligible) consented to participate, and 207 (20%) of these students completed all outcome measures. The average time to complete the computer modules and associated measures was 175 min. Common themes in focus groups with participant students included the desire to contribute to medical education research, the absence of coercion to consent, and the low-risk nature of the research. DISCUSSION: Our findings demonstrate that risk assessment and the extent of review utilized for medical education research vary among IRBs. Despite variability in the perception of risk implied by differing IRB requirements, students themselves felt education research was low risk and did not consider themselves to be vulnerable. The vast majority of eligible medical students were willing to participate as research subjects. Participants acknowledged the time demands of their participation and were readily able to withdraw when those burdens became unsustainable.

Measuring migraine-related quality of care across 10 health plans.

OBJECTIVES: To refine a previously published standardized quality and utilization measurement set for migraine care and to establish performance benchmarks. STUDY DESIGN: Retrospective application of the migraine measurement set to health plan data in order to assess patterns of health service utilization. METHODS: Measurement specifications were applied to data from 10 health plans for measurement year 2009. RESULTS: Of the 2.9 million continuously enrolled members of the health plans, 138,004 (4.7%) met inclusion criteria for the migraine population. Of these, 26% did not have a migraine diagnosis, but were utilizing migraine drugs; 12% had a computed tomography scan within the year (range 8%-25% across plans); and 8% had magnetic resonance imaging (range 6%-11%). Nearly 18% of the migraineurs had 1 or more visits to an emergency department/urgent care center for migraine; few (6%) were followed up with primary care visits. Approximately one-fourth of the migraineurs were not being routinely monitored by a physician. Medication utilization also was examined for members of the migraine population with pharmacy benefits. A significant proportion (42%) were given a migraine preventive, 38% had at least 1 prescription for a triptan, and 2% of those on triptans were potentially overutilizing the medication. Among patients aged 18 to 49 years who were given triptans, 3% had a cardiac contraindication; this percentage rose to 7% for patients aged 50 to 64 years. CONCLUSIONS: This study demonstrates the value of standardized measures in identifying potential quality issues for migraine care, including underdiagnosis, overutilization of imaging, and underutilization of preventive drugs.

Electronic medical records as a research tool: evaluating topiramate use at a headache center.

BACKGROUND: Electronic medical records (EMRs) are used in large healthcare centers to increase efficiency and accuracy of documentation. These databases may be utilized for clinical research or to describe clinical practices such as medication usage. METHODS: We conducted a retrospective analysis of EMR data from a headache clinic to evaluate clinician prescription use and dosing patterns of topiramate. The study cohort comprised 4833 unique de-identified records, which were used to determine topiramate dose and persistence of treatment. RESULTS: Within the cohort, migraine was the most common headache diagnosis (n = 3753, 77.7%), followed by tension-type headache (n = 338, 7.0%) and cluster or trigeminal autonomic cephalalgias (n = 287, 5.9%). Physicians prescribed topiramate more often for subjects with migraine and idiopathic intracranial hypertension (P < .0001) than for those with other conditions, and more often for subjects with coexisting conditions including obesity, bipolar disorder, and depression. The most common maintenance dose of topiramate was 100 mg/day; however, approximately 15% of subjects received either less than 100 mg/day or more than 200 mg/day. More than a third of subjects were prescribed topiramate for more than 1 year, and subjects with a diagnosis of migraine were prescribed topiramate for a longer period of time than those without migraine. CONCLUSIONS: Findings from our study using EMR demonstrate that physicians use topiramate at many different doses and for many off-label indications. This analysis provided important insight into our patient populations and treatment patterns.

Syntactic comprehension deficits are associated with MRI white matter alterations in dementia.

Comprehension difficulties associated with periventricular and deep white matter alterations (WMA) in mild dementia were investigated using portions of the Boston Diagnostic Aphasia Examination (BDAE) Complex Ideation subtest and Syntax subtests. Mild dementia participants were grouped according to the extent of their WMA as observed on magnetic resonance imaging (mild WMA n = 45 vs. moderate to severe WMA n = 52). Correlation and regression analyses also were performed to examine the link between WMA and comprehension abilities, as well as the link between comprehension abilities and neuropsychological measures of executive functioning, language, episodic memory, and overall dementia severity. Results showed that the WMA groups differed on the BDAE-Syntax subtests, with the severe WMA group demonstrating more impairment. Correlation and regression analyses including the entire sample also demonstrated that the extent of WMA was significantly linked to Syntax test scores but not Complex Ideation scores. Regression analyses including neuropsychological measures showed that the BDAE-Complex Ideation score was marginally predicted by only overall dementia severity, whereas the BDAE-Syntax scores were significantly predicted by independent measures of working memory/executive functioning. In conclusion, greater subcortical WMA and executive deficits are associated with greater difficulties in syntactic comprehension in individuals with mild dementia.

Less is not more: underutilization of headache medications in a university hospital emergency department.

OBJECTIVE: To gain knowledge of episodic headache patients who seek care at an urban university emergency department (ED), to evaluate the care they receive and to examine the impact of the ED on these headache patients. BACKGROUND: In the United States, 1% of all ED visits are for the chief complaint of headache. The ED has a significant role in the identification and treatment of primary headache sufferers. METHODS: Patients who presented to the ED with a chief complaint of headache were prospectively administered a patient survey, the PRIME-MD Patient Health Questionnaire, and MIDAS. INCLUSION CRITERIA: any patient 18 years or older with a nontraumatic headache of less than 1 month in duration. The patients included had episodic headache. EXCLUSION CRITERIA: any patient with a history of a lumbar puncture or epidural procedure in the previous 7 days or those with chronic daily headache. Patients who met criteria were asked questions about headache type, health care utilization, satisfaction, co-morbid illnesses, and demographics. A neurologist independently reviewed the ED chart. RESULTS: A total of 219 of 364 patients were eligible and consented. The median age was 34. Most (147, 67.1%) were women; 104 (47.5%) were diagnosed with migraine or probable migraine by chart review; 36% did not have enough information for a neurologist to code a diagnosis. Relatively few headache-specific medications were used 24 hours prior to ED arrival. Only 5% of patients were on headache-preventive medication. Patients commonly received neuroleptics (dopamine antagonists 98 [67.5%]) or opioids (93 [64.1%]) in the ED; however, 74 (33.8%) subjects received neither medication nor IV fluids. Upon leaving the ED, 21.8% were pain free and 89 (40.6%) patients were asked to follow-up with a physician. A total of 137 (62.6%) patients had no documented discharge medications. One person received a prescription for a preventive medication. Sixty-four percent of those who returned the diary reported that the headache returned within 24 hours of leaving the ED. CONCLUSIONS: Migraine ICHD-2 criteria are underused, and patients are undertreated in the ED. Many patients leave without a discharge diagnosis, outpatient medications, or instructions. ED physicians could help identify the migraineurs and channel them toward appropriate outpatient treatment.

International experience, electives, and volunteerism in surgical training: a survey of resident interest.

BACKGROUND: Sustainable international surgery expertise is more frequently being discussed in the US surgical community. At the resident level, there is discussion about incorporating international experience into residency training, but current opportunities for residents are limited and often require personal funding and use of vacation time. This study analyzed resident interest in acquiring international experience. STUDY DESIGN: A structured questionnaire was administered anonymously to all New York University general surgery residents. The questionnaire elicited demographic information and information about interest in an international surgery elective and future volunteerism. Descriptive statistics and chi-square analyses were performed for the completed data. RESULTS: Fifty-two of 63 residents (82.5%) completed surveys. Fifty-one residents (98%) were interested in an international elective, and 38 residents (73%) would prioritize such an elective over all other electives. Twenty-three (44%) and 25 (48%) residents would be willing to use vacation and finance the elective, respectively. The most frequent expectations of international training were acquiring technical and clinical skills (94% of residents) and cultural skills (88%). Residents believed financial difficulties and scheduling conflicts were the most significant barriers to international training (82% and 53%, respectively). Thirty-two residents (62%) planned to incorporate volunteer work into their future practice. Chi-square analyses revealed a significant relationship between residents who would prioritize international training and those who planned to incorporate volunteerism into their future practice (p<0.01). CONCLUSIONS: International training represents an opportunity for US surgical education to provide residents with broader clinical expertise and increased cultural awareness. Our data suggest that surgical residents at NYU are strongly interested in acquiring this experience and that international training may provide an opportunity to encourage lifelong volunteerism. National study of US residents and faculty is warranted to further investigate these conclusions.