Case report: Medical cannabis—warfarin drug-drug interaction

Aim A case of an 85-year-old patient with concurrent use of warfarin and medical cannabis containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is described. Warfarin continues to be a cornerstone of anticoagulation treatment despite the recent addition of FDA-approved anticoagulant agents. It is well known that warfarin has numerous drug interactions; however, much remains unknown about its interaction with THC and CBD. A literature review was conducted to identify documented cases of possible interactions between cannabis and warfarin. The case reports we identified noted that cannabis may potentially increase warfarin’s effect. Therefore, we aimed to determine why an effect was not seen on our patient’s warfarin dose despite daily use of medical cannabis. Case This case report describes an 85-year-old patient who despite starting an oromucosal medical cannabis regimen of THC and CBD (which provided 0.3 mg of THC and 5.3 mg CBD once daily and an additional 0.625 mg of THC and 0.625 mg CBD once daily as needed) had minimal INR fluctuations from October 2018 to September 2019. Conclusion Despite the introduction and use of medical cannabis therapy, with both THC and CBD components, an elderly patient with concurrent warfarin use did not see major INR fluctuations, in contrast to published literature. The potential for warfarin and THC/CBD interactions may be dependent on route of administration and dose of the cannabis product.

Diagnostic accuracy of first and early second trimester multiple biomarkers for prediction of gestational diabetes mellitus: a multivariate longitudinal approach

Background Gestational Diabetes Mellitus (GDM) is an underlying cause of maternal and newborn morbidity and mortality all around the world. Timely diagnosis of GDM plays an important role in reducing its adverse consequences and burden. This study aimed to determine diagnostic accuracy of multiple indicators in complete blood count (CBC) test for early prediction of GDM. Methods In this prospective cohort study, the data from 600 pregnant women was analyzed. In the study sample, the two-step approach was utilized for the diagnosis of GDM at 24–28 weeks of gestation. We also used the repeated measures of hemoglobin (Hb), hematocrit (Hct), fasting blood sugar (FBS) and red blood cell count (RBC) in the first and early second trimesters of pregnancy as the longitudinal multiple indicators for early diagnosis of GDM. The classification of pregnant women to GDM and non-GDM groups was performed using a statistical technique based on the random-effects modeling framework. Results Among the sample, 49 women (8.2%) were diagnosed with GDM. In the first and early second trimester of pregnancy, the mean HcT, Hb and FBS of women with GDM was significantly higher than non-GDMs (P < 0.001). The concurrent use of multiple longitudinal data from HcT, Hb, RBC and FBS in the first and early second trimester of pregnancy resulted in a sensitivity, specificity and area under the curve (AUC) of 87%, 70% and 83%, respectively, for early prediction of GDM. Conclusions In general, our findings showed that the concurrent use of repeated measures data on Hct, Hb, FBS and RBC in the first and early second trimester of pregnancy might be utilized as an acceptable tool to predict GDM earlier in pregnancy.

Determining Risk Factors for Triple Whammy Acute Kidney Injury

Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as "triple whammy". Diuretics and RAS inhibitors, such as an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common. The goals of this study are to better understand the mechanisms underlying the development of triple whammy AKI and to identify physiological factors that may increase an individual's susceptibility. To accomplish these goals, we utilize computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that individual variations in water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI.

Vardenafil Activity in Lung Fibrosis and In Vitro Synergy with Nintedanib

Idiopathic pulmonary fibrosis (IPF) remains an intractably fatal disorder, despite the recent advent of anti-fibrotic medication. Successful treatment of IPF, like many chronic diseases, may benefit from the concurrent use of multiple agents that exhibit synergistic benefit. In this light, phosphodiesterase type 5 inhibitors (PDE5-Is), have been studied in IPF primarily for their established pulmonary vascular effects. However, recent data suggest certain PDE5-Is, particularly vardenafil, may also reduce transforming growth factor beta 1 (TGF-β1) activation and extracellular matrix (ECM) accumulation, making them a potential target for therapy for IPF. We evaluated fibroblast TGF-β1-driven extracellular matrix (ECM) generation and signaling as well as epithelial mesenchymal transformation (EMT) with pretreatment using the PDE5-I vardenafil. In addition, combinations of vardenafil and nintedanib were evaluated for synergistic suppression of EMC using a fibronectin enzyme-linked immunosorbent assay (ELISA). Finally, the effects of vardenafil on fibrosis were investigated in a bleomycin mouse model. Our findings demonstrate that vardenafil suppresses ECM generation alone and also exhibits significant synergistic suppression of ECM in combination with nintedanib in vitro. Interestingly, vardenafil was shown to improve fibrosis markers and increase survival in bleomycin-treated mice. Vardenafil may represent a potential treatment for IPF alone or in combination with nintedanib. However, additional studies will be required.

Gastrointestinal nematodes and Fasciola hepatica in Norwegian cattle herds: a questionnaire to investigate farmers’ perceptions and control strategies

Background Pasture management influences the prevalence and impact of the pasture parasites (PP) in cattle herds, which cause production-limiting disease worldwide. Evaluating farmer management strategies is vital when considering sustainable PP control practices. The aim of this questionnaire-based study was to describe the pasture management and control strategies regarding PP in Norwegian beef cattle (BC) and dairy cattle (DC) production systems with a focus on gastrointestinal nematodes (GIN) and Fasciola hepatica. Results A total of 745 responses from BC (return rate 20.5%) and 1347 responses from DC farmers (30.7%) were included. The mean total pasture time for DC was 4.2 months for first-season grazers and 4.3 months for second-season grazers and cows, while the corresponding finding in BC was 5.4 months. Home pasture was used for most of the pasture period, particularly for first-season grazer dairy heifers (81%), which were also commonly grazed on the same pasture every year (79%). For most farmers it was necessary for grazing areas to be used for cattle for more than one season (77% of BC farmers and 89% of DC farmers). However, changing the pasture during the season was common in both DC (67%) and BC (70%) herds. The majority of DC farmers (60%) stated that they did not consider that they had a problem with PP. Of the remaining 40%, few respondents could specify whether their herds had a problem due to infection by GIN (11%) or liver flukes (12%). Treatment for GIN was performed by 52% of DC and 34% of BC farmers. Diagnostic faecal samples were collected upon suspicion of parasitic disease by 5% of DC and 16% of BC farmers. Veterinarians were stated as a central source of information about parasite management and treatment. Conclusions Potential risks for exposure to PP were identified, such as use of the same pasture every year for first-season grazers and frequent use of home pasture. The perception of problems related to PP appeared low. Regular anthelmintic treatment without concurrent use of diagnostic faecal samples seems to be common practice.

COVID Challenges and Adaptations Among Home-Based Medical Practices: Lessons for an Ongoing Pandemic

Home-based primary care (HBPC) practices rapidly adapted to maintain care during the COVID-19 pandemic. This mixed-methods national online survey of HBPC practices probed responses to COVID-19 surges, COVID-19 testing, the use of telemedicine, practice challenges due to COVID-19, and adaptations to address these challenges. Seventy-nine practices across 29 states were included in the analyses. Eighty-five percent of practices continued to provide in-person care and nearly half cared for COVID-19 patients. Most practices also pivoted to concurrent use of video visits. The top five practice challenges were: patient familiarity with telemedicine, patient and clinician anxiety, technical difficulties reaching patients, and supply shortages. Practices also described creative strategies to physically support the needs of patients. These findings illustrate the need to balance in-person and virtual care for this population, and attend to the emotional needs of patients and staff.

Cannabis at the End of Life: A Road More Traveled

This study examines medical cannabis as a complement or alternative to palliative care (PC). Using cross-sectional survey data from 708 terminal patients in the Illinois Medical Cannabis Program, we compare those in PC (n = 115) to those who are not (n = 593). Increased odds of PC utilization were observed for prior military service, cancer diagnosis, low psychological wellbeing, and medical complexity. PC was positively associated with improvement scores for pain, and ability to manage health status. Higher pain levels were also observed for PC patients who indicated concurrent use of cannabis and opioids, compared to those not using opioids. While most terminal patients use cannabis as an alternative to PC, medical cannabis does operate as a therapeutic complement for individuals in PC to help manage pain and overall health status, and is used at higher levels of pain when patients are also using opioids.

E-cigarettes use behaviors among heavy users in Japan: An online survey (Preprint)

BACKGROUND Electronic cigarette (e-cigarette) use has become increasingly widespread throughout the world, including Japan. However, little is known about how e-cigarettes are used in Japan, a country with heavy restrictions on nicotine-containing e-liquids, vaping products. OBJECTIVE This study comprehensively examined e-cigarette use, including e-cigarette use duration, frequency of use, device type, electrical resistance, nicotine use, favorite e-liquid flavors and concurrent use with cigarettes and/or HTPs in Japan. METHODS This study examined the detail of e-cigarette use (e-cigarette use duration, frequency of use, device type, electrical resistance, nicotine use, favorite e-liquid flavors) among users in Japan, through an online survey using a web-based self-reported questionnaire which included questions about sex, age, combustible cigarette and heated tobacco product (HTP) use behaviors. RESULTS Of 4,689 e-cigarettes users analyzed, 93.5% were men and 52.9% had been using e-cigarettes for 1-3 years. Over 80% used e-cigarettes every day; 62.4% used nicotine liquid, and half of the nicotine liquid users used nicotine salt. The most popular liquid flavor was fruit (prevalence: 68.1%), followed by tobacco (prevalence: 48.4%). While 9.0% were e-cigarette single users, 35.2% were dual users (e-cigarettes and cigarettes or HTPs) and 13.8% were triple user (e-cigarettes, cigarettes and HTPs). CONCLUSIONS This is the first comprehensive survey of Japanese e-cigarette users and our finding suggest more than half use nicotine liquid, although e-cigarettes containing nicotine liquid have been prohibited by the Pharmaceutical Affairs Act since 2010 in Japan. The study also showed 49.1% of participants used cigarettes and/or HTPs concurrently (dual or triple users).

Plasmatic hemostasis at very high altitude — a thrombelas-tometric approach

Introduction: Changes in blood coagulation during exposure to high altitude are not well understood and studies of activation and consumption of specific coagula-tion factors in hypoxic humans have yielded conflicting results. In this study we used thrombelastometry (TEM) which allows a global evaluation of clot formation and lysis process to study blood coagulation profiles in volunteers exposed to pro-longed hypobaric hypoxia at extreme altitudes. Material and methods: We conducted a prospective, observational study in 39 healthy volunteers during a research expedition up to an altitude of 7050 m. Plasma based thrombelastometric measurements and standard coagulation parameters were performed at different altitudes. Results: TEM measurements showed an increase in clotting time (CT) and maxi-mum clot firmness (MCF) at high altitudes, paralleled by an increase in international normalized ratio (INR) and activated partial thromboplastin time (aPTT). Fibrinogen concentration increased until 6022 m. D-Dimer and Thrombin-Antithrombin complex (TAT) increased with time exposed to severe hypoxia. For both measurements highest levels were found at 4844 m after acclimatization; in contrast, lower values were observed again at 7050m in the group of summiteers. Activated protein C resistance (APC-R) was slightly lowered at all altitudes. Conclusion: Our results suggest that activation of the coagulation and fibrinolytic system occurs with increasing hypobaric hypoxia with concurrent use of coagula-tion factors indicating the occurrence of a consumption-coagulopathy phenotype.