Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

Introduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. Methods: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, "responders" (≥30% reduction in weekly pain at any time point) were identified. Results: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months (F(3,450) = 26.22, P < 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were "responders" but could not be identified by baseline parameters. "Responders" exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious. Conclusion: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.

Characteristics and clinical needs of young tertiary students attending a specialist mood disorders clinic.

OBJECTIVE: To investigate the clinical characteristics of tertiary students and non-students attending a specialist clinic for severe mood disorders. METHOD: Medical record audit of clients discharged from the Youth Mood Clinic (YMC). Data extracted included depressive symptomatology, suicidal ideation, self-harm, suicide attempt, tertiary education engagement, drop-out and deferral. RESULTS: Data from 131 clients (M age = 19.58 years, SD = 2.66) were analysed, including 46 tertiary students. Relative to non-students, at intake, tertiary students reported more severe depressive symptomatology (d = 0.43). They were more likely to experience suicidal ideation at intake (V = 0.23), and during treatment (V = 0.18). Tertiary students were also more likely to be living separately to their family of origin (V = 0.20) but were less likely to have experienced parental separation (V = 0.19). 21.73% of tertiary students dropped out or deferred study during care. CONCLUSION: In this cohort, those engaged in tertiary education experience more severe depression and more commonly experienced suicidal ideation. These young people require targeted support for their mental health while they undertake tertiary education.

High degree atrio-ventricular block following COVID-19 vaccination.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in more than four million deaths globally. In addition to the lower respiratory system, a wide range of major organ injuries have been reported among patients infected with COVID-19. These injuries include cardiac involvement. The spectrum of cardiac manifestations includes cardiac injury, heart failure, cardiogenic shock, acute coronary syndrome, myocarditis, tachyarrhythmias, and bradyarrhythmia [1]. Different degrees of atrioventricular blocks have been reported [2]. The pathogenesis of these complications is not fully understood. Different mechanisms are proposed, including direct myocyte injury, interstitial inflammation and fibrosis, cytokine storm, plaque destabilization, and and/or hypoxia [3]. Many countries have worked toward mass vaccination using the Pfizer BioNTech (BNT162b2) COVID-19 vaccine, including Israel. We report a case of high degree atrioventricular block (AVB) following vaccination with the COVID-19 BNT162b2 vaccine.

Effect of intramuscular depot betamethasone injection in patients with fibromyalgia and elevated C-reactive protein levels.

Fibromyalgia is characterized by diffuse musculoskeletal pain and fatigue. There are limited data about systemic steroid treatment of patients with fibromyalgia in the English literature. Patients with fibromyalgia with ongoing diffuse musculoskeletal pain despite standard treatment, extreme fatigue and elevated C-reactive protein (CRP) levels without evidence of synovitis, or other source of inflammation, were asked to participate in our study. After consent, demographic, clinical and laboratory parameters in addition to body mass index were documented. These patients were interviewed and asked to answer the Revised Fibromyalgia Impact Questionnaire (FIQR) just prior, 1 and 4 weeks following 14 mg depot betamethasone intramuscular injection. Twenty-three patients were recruited and 21 completed the study. 19 patients were women with mean age of 42±10.12 and CRP level of 14.1±3.96 mg%, and all had negative rheumatoid factor and antinuclear antibodies. All patients had significant improvement in all of the FIQR parameters, at 1 and 4 weeks, except memory, anxiety and balance. It can be concluded that systemic intramuscular depot betamethasone injection seems to have a favorable effect in patients with fibromyalgia with elevated CRP levels for at least 4 weeks.

Global improvement in meibomian glands after chalazion surgery demonstrated by meibography.

PURPOSE: To evaluate the use of meibography as an objective measure of the effects of incision & curettage (I&C) chalazion surgery on meibomian gland loss and morphology as well as dry eye syndrome. METHODS: This prospective, interventional clinical study included adult patients with a primary chalazion which persisted despite conservative treatment. All patients underwent I&C surgery. The following parameters were compared both preoperatively and 21 days postoperatively: meibography, tear breakup time (TBUT), Schirmer test, meibum expression, tear meniscus height, meibomian gland dysfunction (MGD) grading, and the Ocular Surface Disease Index (OSDI). RESULTS: Thirty eyelids were enrolled in the study. The mean age ± SD was 40.56 ± 13.94 years. Meibography demonstrated a significant decrease in meibomian gland loss (P = 0.00) and improvement in morphology. The most common meibomian gland pathology preoperatively noted was morphological signs of atrophy that included fluffy areas and tortuous glands. Both of these findings improved postoperatively (P = 0.04 and P = 0.02, respectively). There were a significant change in MGD grading and a significant decrease in meibum expression score postoperatively (P = 0.00). TBUT and tear meniscus height also improved significantly (P = 0.00 and P = 0.003, respectively). The OSDI score improved significantly as well (P = 0.00). CONCLUSION: While incision and drainage surgery is a time-honored, standard treatment for chalazion, meibography now demonstrates a global improvement in the meibomian glands, not just the ones involved with the chalazion. In addition to the improvements in the clinical and dry eye syndrome parameters improvements, meibography findings demonstrate that early I&C surgery restores the meibomian glands architecture significantly.

Metabolic effects of medical cannabis treatment.

Cannabis has a wide range of favorable clinical effects on pain, sleep, mood, gastrointestinal symptom, appetite and physical activity, factors that may affect the metabolic profile of the consumer. In this study, we prospectively evaluated patients recently starting medical cannabis treatment. All patients from the rheumatology clinic, who were just approved for medical cannabis treatment for resistant chronic pain, were recruited. After consent, demographic and clinical parameters were documented, including indication for medical cannabis treatment, way of consumption, type of cannabis and monthly dose of medical cannabis. Fasting morning blood glucose, hemoglobin A1c, insulin, lipid profile, cortisol and uric acid levels, in addition to body weight, were obtained just prior to and 3 months following cannabis consumption. Wilcoxon' sign rank test was used to compare baseline levels to those obtained 3 months later. Twenty-eight patients completed the study. Mean age of the patients was 47.8±9.1 years and ~70% were female patients. 75% of all the patients had fibromyalgia. Mean monthly consumed cannabis amount was 22.21±3.6 g, and 21 (75%) patients used extracts (oil). There was no significant change in any parameter evaluated. The results of our study seem to indicate that medical cannabis, mainly extracts, have no significant effect on any parameter of the metabolic profile of patients with chronic pain syndrome, during 3 months of initial use.

The Effect of Medical Cannabis on Pain Level and Quality of Sleep among Rheumatology Clinic Outpatients.

Introduction: Medical cannabis (MC) is becoming increasingly popular for the treatment of chronic pain conditions. In this study, we evaluated the effect of MC treatment on pain level and quality of sleep of patients with different medical conditions at the rheumatology clinic. Methods: Patients licensed for the use of MC at the rheumatology clinics at different settings were located and contacted. Their demographic and clinical parameters were documented, including type of medical cannabis consumed, way of consumption, and current monthly consumed amount. These patients were contacted by phone and asked about the effect on pain level and quality of sleep. Results: A total of 351 patients were located, and 319 completed the questionnaire. Mean age was 46 ± 12 years, 76% were female, 82% had fibromyalgia, ∼9% had mechanical problems, ∼4% had inflammatory problems, ∼4% had neurological problems, and ∼1% had other problems. The average monthly consumed dose of MC was 31, 35, 36, and 32 g, with mean pain level reduction of 77%, 82%, 83%, and 57%, and mean sleep quality improvement of 78%, 71%, 87%, and 76% among patients with fibromyalgia, mechanical, neuropathic, and inflammatory problems, respectively. Mean THC and CBD contents were 18.38% ± 4.96 and 2.62% ± 4.87, respectively. The THC concentration, duration of MC consumption, and MC consumption dose had independent significant correlations with pain reduction while only the duration of MC consumption had an independent significant correlation with sleep quality improvement. Conclusions: MC had a favorable effect on pain level and quality of sleep among all spectrums of problems at the rheumatology clinic.

Initial Presentation of Pain in Patients with Fibromyalgia.

BACKGROUND: Fibromyalgia is characterized by diffuse musculoskeletal pain at the time of diagnosis, but many patients report their initial symptoms as being focal or local. OBJECTIVES: To evaluate, prospectively, the initial location of body pain in recently diagnosed patients with fibromyalgia. METHODS: Non-selected patients from the rheumatology clinic who were recently diagnosed with fibromyalgia (≤ 2 years) with symptoms of ≤ 4 years participated in our study. Demographic and clinical parameters were documented, as was the initial location of pain they had experienced. Sub-analysis of data according to gender and ethnicity was conducted using chi-squire test. RESULTS: The study comprised 155 patients. Mean age was 39.8 ± 11.7 years; 85% were female. Mean duration of symptoms was 2.11 years and of diagnosis was 0.78 years. Six patients (3.9%) reported initial symptoms of pain as being diffuse from the start, 10 (6.5%) could not remember the location of their initial symptoms, and 139 (90%) reported initial focal pain. Hands were reported as the initial area of pain for 25.2% of the patients, 19.4% reported the back, and 11% reported both trapezial areas as the initial area of pain. In 90% of the patients (excluding patients with back, abdominal, or chest pain) the initial symptoms were bilateral and symmetrical. No significant difference in initial presentation was found among different gender or ethnic groups. CONCLUSIONS: Pain in fibromyalgia patients usually presents as focal and symmetrical. Bilateral hand pain, followed by back pain, was the most common reported area of initial pain among fibromyalgia patients.

High utilisers of emergency departments: the profile and journey of patients with mental health issues.

OBJECTIVE: Frequent presenters to the Emergency Department (ED) are known to have complex physical, behavioural and social needs. The study aimed to analyse the system's behaviour to generate new insights into ED high utilisers with complex mental health issues. METHODS: A retrospective cohort study of the ED presentations of 200 high utilisers during a 12-month period was conducted. Analyses included psychiatric diagnoses, re-presentation rates, cost-benefit analysis of services and patient journey maps to illustrate the patient experience. RESULTS: The profiled high utilisers represented nearly a quarter of total ED mental health presentations and were more likely to be single and unemployed. Diagnostically, Borderline Personality Disorder and Schizophrenia predominated. The re-presentation rate was high (70% within 28 days) and mental health attributable costs represented nearly three quarters of total health costs. CONCLUSION: The study revealed a disintegrated service system for ED high utilisers with mental health issues, resulting in suboptimal clinical outcomes and substantial costs. To deliver value-based mental healthcare our lessons were; (1) stabilise the system's interaction with the patient by ensuring service responses are consistent with their enhanced management plan (2) all the system's parts channel the patient into various support services including psychological treatment with one therapist.KEY POINTSThe top 200 high utilisers presented to emergency 1928 times within 12 monthsThe re-presentation rate amongst the study's cohort was high (70% within 28 days)A high prevalence of BPD and schizophrenia was noted for this cohortThe study reveals a disintegrated service system for ED high utilisers, resulting in suboptimal clinical outcomes and substantial costs for the serviceA need for early identification, consistency in service responses and various support services to be provided by the hospital including psychological treatment.

The impact of medical cannabis consumption on the oral flora and saliva.

OBJECTIVE: To evaluate the effect of medical cannabis consumption on oral flora and saliva. DESIGN: A clinical prospective study, at the rheumatology clinic of the Nazareth Hospital in Nazareth, recruiting consecutively patients approved for medical cannabis, evaluating their saliva flow, pH and microbial load of Streptococcus mutans and Lactobacillus, prior to and under medical cannabis treatment. METHODS: Patients recently licensed for medical cannabis treatment, were recruited just prior to starting medical cannabis consumption (week 0), 1 and 4 weeks later, patients provided 5-minute time saliva samples, which were measured for their volume and pH, and cultured on a special microbial kit, evaluating the growth of Streptococcus mutans and Lactobacillus. RESULTS: Out of 16 patients enrolled, 14 were female and had fibromyalgia. The mean age of the patients was 52.8±12.9 years. The mean saliva flow at week 0, week 1 and week 4 were 5.38±3.36 ml/5-minutes, 6 (p = 0.769) and 5.45 (p = 0.391), respectively, and for saliva pH were 6.28, 5.94 (p = 0.51) and 5.5 (p = 0.07) respectively also. The mean Streptococcus mutans growth score at weeks 0, 1 and 4 was1.8±0.75, 1.6±0.83 (p = 0.234), and 2.4±0.84 (p = 0.058), respectively. The mean Lactobacilli growth score at weeks 0, 1 and 4 was 2.59±0.88, 3.1±0.69 (p = 0.033) and 3.3±0.67 (p = 0.025), respectively. CONCLUSIONS: The results of this study show that medical cannabis consumption has no significant effect on saliva volume or pH, but it may be associated with changes in salivary levels of oral microbes such as Streptococcus mutans and Lactobacilli.

[CHARACTERISTICS OF MEDICAL CANNABIS USAGE AMONG PATIENTS WITH FIBROMYALGIA].

INTRODUCTION: Medical cannabis (MC) is becoming more and more popular among patients with chronic pain syndromes. In this study we evaluated the characteristics of MC use among patients with fibromyalgia. METHODS: All patients with fibromyalgia who were followed up at Laniado Hospital in Netanya and at the Nazareth Hospital in Nazareth, in addition to all patients followed at the different health service organizations by the first author were located and contacted regarding a large number of parameters. The data included demographic information, duration of fibromyalgia symptoms and diagnosis, duration of MC use, monthly consumption of MC, frequency of daily use, number of species of MC currently used, number of species previously used, types and features of MC supplied, methods of MC consumption, delay in MC supply, symptoms of cannabis withdrawal during delay in supply or shortage of MC, familiarity with the content of (-)- trans-Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) of the current species used. Furthermore, information was retrieved on current medications for fibromyalgia and medications for fibromyalgia stopped after starting MC consumption, discontinuation of MC treatment, companies growing and supplying the currently consumed MC, names of current MC species, dominance of Sativa or Indica of the current MC species, and the impact of MC on clinical parameters such as pain, sleep, anxiety, depression, memory, concentration and weight. In addition, questions were presented regarding work, outdoor leisure time, driving, sharing their own MC with other people, opinion on the reform of MC in Israel and adverse effects of MC. RESULTS: One-hundred and one patients completed the study; 73% of the participants were female with a mean age of 45±11.8 years. The mean duration of fibromyalgia symptoms and diagnosis were 8.39±6 and 4.69±3.9 years, respectively. The mean duration of MC consumption was 15.3±12.6 months and the mean monthly consumption amount was 28.6±10.2 g. 54% smoked pure cannabis, 18% used vaporized cannabis only and 3 participants only used MC oil. The rest used a variety of combinations. The mean minimal daily frequency of MC consumption was 4.11±2.9 times and the mean maximal daily frequency was 7.9±5.6 times. The mean number of current daily MC species was 2.11±1 and the mean number of tried species was 6.7±5.2 for each participant; 47% of all the participants stopped any other treatment for fibromyalgia and 51% reduced the dose or the number of other medications for fibromyalgia. One patient only stopped MC treatment. Tikun Olam was the manufacturing company with the largest number of clients and its most popular species for daytime was "Alaska" and "Erez" for night-time. Mean improvement in sleep and pain was slightly more than 77% with less improvement in other parameters; 36% of the patients reported weight gain, while 16% reported weight loss; 51% reported having more leisure time outdoors. Nearly all patients refused sharing any amount of their MC with friends or family members, and all patients recommended MC treatment for their loved ones once they develop severe fibromyalgia; 61% of the participants were against the reform of MC and 11% were in favor of it. Nearly one quarter of the patients reported mild adverse effects and one patient developed a psychotic attack (was consuming 70 gram of MC monthly). CONCLUSIONS: MC is an effective treatment for fibromyalgia, with nearly zero % withdrawal from this treatment. The mean daily amount consumed was relatively low, less than 1 gram, and the main method of consumption was smoking with a huge variety in the frequency of smoking during the day and night among the participants. MC treatment enabled nearly half of the patients to discontinue any treatment for fibromyalgia and all participants recommended MC treatment for their loved ones in case they develop severe fibromyalgia. Most participants were against the reform of MC in Israel. Mild adverse effects were reported in nearly a quarter of the patients but did not result in discontinuing its consumption.

[THE IMPACT OF ADMISSION TO THE MEDICAL WARD ON HEMOGLOBIN A1C LEVELS AMONG PATIENTS WITH TYPE-2 DIABETES].

INTRODUCTION: Blood glucose monitoring is a routine medical practice in the medical ward regardless of the cause of hospitalization of patients with diabetes. In this study we prospectively evaluated the impact of hospitalization on hemoglobin A1c (HbA1c) among patients with type-2 diabetes admitted to the medical ward, for reasons unrelated directly to their diabetes. METHODS: Patients with type-2 diabetes who were admitted to the medical ward for reasons not directly related to diabetes were asked to participate in our study. After consent , demographic, clinical and laboratory parameters were documented on admission, including age, sex, social status, years of study, duration of diabetes, type of anti-diabetic treatment, background medical problems and treatment, diagnosis on admission, temperature, blood glucose levels on admission to the medical ward, complete blood count and serum creatinine. In addition, HbA1c levels on admission, first 24-hour blood glucose levels at the medical ward, change of therapeutic treatment of their diabetes, diagnosis at discharge and recommended medication at discharge, were also documented. Three months following admission, the HbA1c study was repeated again. Paired t-test and Wilcoxon's rank sign test were used to compare between HbA1c levels at baseline and 3 months later among all the patients and among the subgroups. Multivariate regression analysis was used also to predict change in HbA1c levels among these patients. Physicians taking care of the patients on the medical ward were not aware of the study. RESULTS: Forty-four patients were recruited and 40 patients completed the study. There were 24 men (60%), with a mean age of 69.625±11.53 years for all the patients. The most common diagnosis on admission was infection followed by congestive heart failure. Mean 24-hour blood glucose level following admission was 209 mg% ±95. Among 12 patients there was an augmentation in diabetes treatment and in 3 there was dis-augmentation/discontinuation. Mean hemoglobin A1c levels on admission and 3 months later was 7.29% and 6.80% respectively (p=0.095). However, sub-analysis of patients with HbA1c levels >7.5% on admission, showed a significant decrease in the repeated HbA1c levels (p=0.003). CONCLUSIONS: Medical ward admission was associated with reduced HbA1C levels, yet not significant, among patients with type-2 diabetes who were admitted for reasons not directly related to diabetes.

Medical Cannabis in Treatment of Resistant Familial Mediterranean Fever.

BACKGROUND Colchicine-resistant familial Mediterranean fever can be treated by anti-IL-1 biologic therapy; however, such treatment needs approval by the health insurance company, and many patients are denied such treatment or do not respond to it. CASE REPORT Two familial Mediterranean fever (FMF) patients, both homozygous for M694V mutation and resistant to colchicine treatment, were treated with medical cannabis. Prior to that, 1 patient was denied biologic treatment and the other had no significant response to anakinra. Under medical cannabis treatment, both patients had remarkable improvement in the severity of the attacks and also a decrease in the frequency of the attacks, from once every 2 weeks to 1 attack every month in 1 patient; this patient had also a remarkable reduction in the C-reactive protein level during the attacks. CONCLUSIONS Cannabis is a therapeutic option for treating the most complex patients with FMF.

The Effect of Periarticular Injection of Methylprednisolone Acetate in Patients with Primary Osteoarthritis of the Proximal Interphalangeal Joints: A Case Controlled Study.

BACKGROUNDS: Primary osteoarthritis of the proximal interphalangeal joints (PIPJ) is a common entity. It could be associated with local pain that has no effective treatment. Local subcutaneous periarticular injection of methylprednisolone acetate (MPA) was evaluated in a prospective case-control study. METHODS: Patients with painful osteoarthritis of the PIPJ for more than 1 month not responding to nonsteroidal meds were prospectively recruited. Radiographic, demographic, clinical, and lab parameters were documented. Visual analogue scale (VAS) was documented regarding the level of PIPJ pain prior to the injection. Patients had local subcutaneous periarticular injection at the medial and lateral sides of each painful PIPJ of one hand, of 8 mg (0.2 ml) of MPA mixed with 0.1 ml of lidocaine 1% (group 1) at each side. Age- and sex-matched control group were given 0.3 ml of normal saline using the same approach (group 2) at each side. VAS was evaluated 1, 4, and 10 weeks following the injection and compared to baseline levels using Wilcoxon's ranks signed test. RESULTS: Eighteen and sixteen patients were recruited in group 1 and group 2, respectively. There were 11 females in group 1 with mean age of 52.7 ± 9.2 years. Mean VAS in group 1 at baseline was 67 and at weeks 1, 4, and 10 was 23 (p=0.001), 29 (p=0.001), and 55 (p=0.043), respectively. Mean VAS in group 2 at baseline was 65 and at weeks 1, 4, and 10 was 43 (p=0.005), 64 (p=0.534), and 69 (0.698), respectively. CONCLUSIONS: Subcutaneous periarticular injection of MPA + lidocaine at the PIP joints resulted in a small but significant improvement that gradually diminished with time across the week 10, among patients with primary OA of hands.

Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study.

Objective: Approximately 30% of patients with type 2 diabetes mellitus have knee osteoarthritis. IA corticosteroids used to manage osteoarthritis pain can elevate blood glucose in these patients. We compared blood glucose levels following intra-articular injection of triamcinolone acetonide extended-release (TA-ER), an extended-release, microsphere-based triamcinolone acetonide formulation, vs standard triamcinolone acetonide crystalline suspension (TAcs) in patients with knee osteoarthritis and comorbid type 2 diabetes. Methods: In this double-blind, randomized, parallel-group, phase 2 study (NCT02762370), 33 patients with knee osteoarthritis (American College of Rheumatology criteria) and type 2 diabetes mellitus (HbA1c 6.5-9.0% [48-75 mmol/mol]; 1-2 oral hypoglycaemic agents) were treated with intra-articular TA-ER (32 mg n = 18) or TAcs 40 mg (n = 15). Continuous glucose monitoring-measured glucose (CGMG) was assessed from 1 week pre-injection through 2 weeks postinjection. Endpoints included change in average daily CGMG from baseline (days -3 to -1) to days 1-3 postinjection (CGMGdays1-3) (primary) and percent time average hourly CGMG levels remained in prespecified glycaemic ranges. Results: The change CGMGdays1-3 was significantly lower following TA-ER vs TAcs (14.7 vs 33.9 mg/dl, least-squares-mean-difference [95% CI]: -19.2 [-38.0, -0.4]; P = 0.0452). The percentage of time over days 1-3 that CGMG was in the target glycaemic range (70-180 mg/dl) was numerically greater for TA-ER (63.3%) vs TAcs (49.7%), and that CGMG was >180 mg/dl was lower for TA-ER (34.5%) vs TAcs (49.9%). Non-glycaemic adverse events were mild and comparable between groups. Conclusion: TA-ER may enable intra-articular corticosteroid treatment with minimal blood glucose disruption in patients with knee osteoarthritis and type 2 diabetes mellitus. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02762370.