Early intervention treatment in the first 2 weeks following concussion in adults: A systematic review of randomised controlled trials.

OBJECTIVE: International guidelines support a repertoire of therapeutic interventions that may assist recovery following concussion. We aimed to systematically review the efficacy of early pharmacological and non-pharmacological interventions initiated within two weeks of injury on symptoms and functional recovery of adults with concussion. METHODS: We conducted a Systematic Review (SR) of Randomised Controlled Trials (RCTs) without meta-analysis utilising the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed of four databases. Study inclusion criteria were adult participants diagnosed with concussion and commencing active intervention within 14 days of injury. RESULTS AND CONCLUSIONS: Of 7531 studies identified, 11 were included in the final review. Six studies were rated as high-risk of bias, three with some concerns and two as low-risk of bias. We found no evidence to support specific pharmacotherapeutic management to hasten the natural recovery time-course. Two studies reported significant improvement in selected concussion symptoms following manual therapy (at 48-72 hours post-treatment) or telephone counselling interventions (at 6 months post-injury). No high quality RCTs demonstrate superior effects of early therapeutic interventions on concussion recovery in the first 2 weeks. We advocate future research to examine impacts of health-clinician contact points aligned with symptom-specific interventions.

Adapting an evidence-based mindfulness-based intervention for sheltered youth experiencing homelessness.

OBJECTIVES: Youth experiencing homelessness (YEH) face challenges that impact their physical, mental, and social wellbeing, emotion regulation, and coping. Mindfulness reduces stress and improves resilience, emotion regulation, and executive functioning. Mindfulness-based interventions (MBI) teach the practice of mindfulness to foster present-moment attention without judgement and enhance self-observation and self-regulation, resulting in greater awareness of thoughts and emotions and improved interpersonal relationships. One such intervention, .b, has been shown to lower stress among youth. While a pilot study of .b among sheltered youth found the intervention to be feasible, the need for modifications was identified to improve its relevance, accessibility, and incorporate a trauma-informed approach. METHODS: We used the ADAPT-ITT (Assessment, Decisions, Administration, Production, Topical experts, Integration, Training staff, and Testing) framework to adapt the .b mindfulness intervention to YEH living in an emergency shelter. Nine focus group discussions (n = 56), key informant interviews (n = 8), and beta testing with five youth working group sessions (n = 10) identified needed modifications. RESULTS: Adaptations to the curriculum and delivery modality were made to approximate the average length of stay in the shelter; integrate trauma-informed care approaches; increase diversity of images by race, ethnicity, age, sexual orientation, and gender identity; and increase the relevance of the audio-visual components. CONCLUSIONS: Youth and the health and social services providers who care for youth generally liked the core concepts and presentation of the curriculum. Using the ADAPT-ITT framework, minor, yet important, changes were made to increase the relevance, acceptability, and feasibility of the intervention. Next steps are to conduct a randomized attention control pilot study to assess feasibility and acceptability.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Treatment Landscape.

The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies-particularly in persons with Crohn's disease-combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time. The substantially increased costs associated with targeted therapies has led to a ballooning of healthcare expenditure to treat IBD over the past 15 years. The introduction of less expensive biosimilar anti-tumour necrosis factor therapies may bend this cost curve downwards, potentially allowing for more widespread access to these medications. Newer therapies targeting different inflammatory pathways and complementary and alternative therapies (including novel diets) will continue to shape the IBD treatment landscape. More precise use of a growing number of targeted therapies in the right individuals at the right time will help minimize the development of expensive and disabling complications, which has the potential to further reduce costs and improve outcomes.

Implementing and Evaluating the Impact of BoneRx: A Healthy Bone Prescription for Men with Prostate Cancer Initiating Androgen Deprivation Therapy.

Background: The initiation of Androgen Deprivation Therapy (ADT) results in rapid and profound hypogonadism, resulting in significant bone and muscle loss, increasing the risk for osteoporosis (OP), falls, and fractures. Despite this, there exist very low rates of guideline adherent care regarding bone health in this population. We developed and implemented a healthy bone prescription tool entitled BoneRx to facilitate the uptake of guideline-concordant bone health care into practice and increase patient awareness and promote the uptake of health bone behaviours (HBBs). Methods: We conducted a cross-sectional pre-BoneRx implementation (n = 143) vs. post-implementation (n = 149) cohort study to evaluate the impact on (i) bone health care, patient engagement in HBB, and patient knowledge and health beliefs regarding OP. Results: There was a significant difference pre- vs. post BoneRx implementation on receipt of baseline BMD (34.7% vs. 59.5%, p < 0.0001) and bone health counselling (32.4% vs. 59.9%, p < 0.0001). More participants in the post-BoneRx implementation cohort reported taking vitamin D supplements 57% vs. 81% (p < 0.001) and calcium supplements 39% vs. 61% (p < 0.001). Physical activity levels also significantly increased (p = 0.021). No differences were detected in OP knowledge or feelings of OP susceptibility, seriousness, or health motivation. Conclusion: BoneRx is a simple, cost-effective, and acceptable strategy that could improve the care of PCa survivors receiving ADT.

Crohn's and Colitis Canada's 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Health Care Delivery During the Pandemic and the Future Model of Inflammatory Bowel Disease Care.

The SARS-CoV-2 pandemic has had a profound impact on inflammatory bowel disease (IBD) health care delivery. The implementation of necessary public health restrictions has restricted access to medications, procedures and surgeries throughout the pandemic, catalyzing widespread change in how IBD care is delivered. Rapid large-scale implementation of virtual care modalities has been shown to be feasible and acceptable for the majority of individuals with IBD and health care providers. The SARS-CoV-2 pandemic has exacerbated pre-existing barriers to accessing high-quality, multidisciplinary IBD care that addresses health care needs holistically. Continued implementation and evaluation of both synchronous and asynchronous eHealthcare modalities are required now and in the future in order to determine how best to incorporate these modalities into patient-centred, collaborative care models. Resources must be dedicated to studies that evaluate the feasibility, acceptability and effectiveness of eHealth-enhanced models of IBD care to improve efficiency and cost-effectiveness, while increasing quality of life for persons living with IBD. Crohn's and Colitis Canada will continue to play a major leadership role in advocating for the health care delivery models that improve the quality of life for persons living with IBD.

Factors Influencing Preference for Intervention in a Comparative Effectiveness Trial of Mindfulness-Based Cancer Recovery and Tai Chi/Qigong in Cancer Survivors.

Introduction: An important gap between randomized efficacy research and real-world implementation of complementary therapies is the role of patient preferences in influencing engagement and outcome. Several studies have highlighted the benefits of patient preference on health outcomes, but few have investigated the factors associated with preference for interventions, which may be critical to assure the success of program implementation. The current study sought to explore the factors associated with patient preference in an ongoing randomized preference-based trial of Mindfulness-Based Cancer Recovery (MBCR) versus Tai Chi/qigong (TCQ) (the Mindfulness and Tai Chi/qigong in Cancer Health [MATCH] study). Materials and Methods: A multi-method study design was used. A subsample of participants were purposely selected from the ongoing MATCH study to have representation from both intervention arms and from both men and women across different age groups. Open-ended, semi-structured qualitative interviews were conducted to explore the factors influencing initial patient preference. Interviews were transcribed verbatim and analyzed by using inductive thematic analysis. The treatment acceptability and preference measure was administered to determine patients' ratings of acceptability and credibility of both preferred and nonpreferred interventions. Results: A total of 13 participants were interviewed prior to program attendance, with 8 (62%) preferring TCQ and 5 (38%) choosing MBCR. Major themes related to patients' preference for intervention included: (1) expectations about the preferred intervention; (2) knowledge of the intervention; (3) past experiences with the intervention; and (4) self-efficacy. Participants' mean treatment acceptability scores were higher for their preferred program than their nonpreferred program. Conclusion: Understanding the factors that influence cancer survivors' preference for mind-body interventions can augment health care providers' knowledge of the barriers and facilitators for successful implementation of interventions in clinical settings, as well as help patients make informed treatment decisions and improve satisfaction and outcomes. Clinical trial registration no.: NCT03641222.

Cooking for Vitality: Pilot Study of an Innovative Culinary Nutrition Intervention for Cancer-Related Fatigue in Cancer Survivors.

(1) Background: Cancer-related fatigue (CRF) is one of the most prevalent and distressing side effects experienced by patients with cancer during and after treatment, and this negatively impacts all aspects of quality of life. An increasing body of evidence supports the role of poor nutritional status in the etiology of CRF and of specific diets in mitigating CRF. We designed a group-based two session culinary nutrition intervention for CRF, Cooking for Vitality (C4V), aimed at increasing understanding of how food choices can impact energy levels and establishing basic food preparation and cooking skills as well as the application of culinary techniques that minimize the effort/energy required to prepare meals. The purpose of this pilot mixed-method study was to evaluate: Feasibility of the experimental methods and intervention; acceptability and perceived helpfulness of intervention; and to obtain a preliminary estimate of the effectiveness of the intervention on fatigue (primary outcome), energy, overall disability, and confidence to manage fatigue (secondary outcomes). (2) Methods: Prospective, single arm, embedded mixed-methods feasibility study of cancer survivors with cancer-related fatigue was conducted. Participants completed measures at baseline (T0), immediately following the intervention (T1), and three months after the last session (T2). Qualitative interviews were conducted at T2. (3) Results: Recruitment (70%) and retention (72%) rates along with qualitative findings support the feasibility of the C4V intervention for cancer survivors living with CRF (program length and frequency, ease of implementation, and program flexibility). Acceptability was also high and participants provided useful feedback for program improvements. Fatigue (FACT-F) scores significantly improved from T0-T1 and T0-T2 (p < 0.001). There was also a significant decrease in disability scores (WHO-DAS 2.0) from T0-T2 (p = 0.006) and an increase in POMS-Vigor (Profile of Mood States) from T0-T1 (p = 0.018) and T0-T2 (p = 0.013). Confidence in managing fatigue improved significantly from T0-T1 and T0-T2 (p < 0.001). (4) Conclusions: The results suggest that the C4V program was acceptable and helpful to patients and may be effective in improving fatigue levels and self-management skills. A randomized controlled trial is required to confirm these findings.

Development, implementation, and effects of a cancer center's exercise-oncology program.

BACKGROUND: National and international bodies acknowledge the benefit of exercise for people with cancer, yet limited accessibility to related programing remains. Given their involvement in managing the disease, cancer centers can play a central role in delivering exercise-oncology services. The authors developed and implemented a clinically integrated exercise-oncology program at a major cancer center and evaluated its effectiveness and participant experience. METHODS: A hospital-based program with prescribed at-home exercise was developed and accepted referrals over a 42-month period (3.5 years). Implementation was conducted in 2 phases: a pilot phase for women with breast cancer and men with genitourinary cancer and a roll-out phase for all patients with cancer. Enrolled patients were assessed and received an exercise prescription as well as a program manual, resistance bands, and a stability ball from a kinesiologist. Program participation and effectiveness were evaluated up to 48 weeks after the baseline assessment using intention-to-treat analyses. Participants in the roll-out phase were asked to complete a program experience questionnaire at the completion of the 48-week follow-up. RESULTS: In total, 112 participants enrolled in the pilot, and 150 enrolled in the roll-out phase. Program attrition to 48 weeks was 48% and 65% in the pilot and roll-out phases, respectively. In participants who consented to research evaluation of their performance, objective and patient-reported measures of functional capacity improved significantly from baseline in both phases. Participants were highly satisfied with the program. CONCLUSIONS: Despite significant drop-out to program endpoints, our cancer-exercise program demonstrated clinically relevant improvement in functional outcomes and was highly appreciated by participants.

A scoping review of rehabilitation interventions for survivors of head and neck cancer.

Purpose: The objectives of this scoping review were to summarize, understand, and disseminate findings from a broad body of literature on rehabilitation interventions used with survivors of head and neck cancer. Method: Searches were conducted in six databases. Inclusion criteria were studies of adult head and neck cancer survivors with a predefined primary rehabilitation outcome as a result of an intervention. Excluded were studies not written in English, opinion papers, or studies where the intervention was not carried out by a rehabilitation healthcare service. A second level, full-text review of the studies was conducted. A thematic analysis was used to examine and combine study findings. Results: A total of 3804 results were retrieved from all sources resulting in 39 papers that were analyzed. The thematic analysis of the included papers represented interventions focusing on swallowing and nutrition, speech, physical therapy, assistive devices, complementary and alternative modalities, comprehensive interdisciplinary programs, and preventive rehabilitation programs. Conclusion: This review has provided an overview of the scope of rehabilitation interventions available for survivors of head and neck cancer and preliminary information about their efficacy. This is foundational information for the development and refinement of rehabilitation interventions and programs for head and neck cancer survivors. Implications for Rehabilitation The existing evidence suggests that survivors of head and neck cancer can benefit from early screening of potential rehabilitation needs and being involved in preventive rehabilitation programs pre-surgery when possible. Rehabilitation programs should consider swallowing interventions for patients as evidence reports improved swallowing function, decreased pain and discomfort, and reduced duration of feeding tube use. Rehabilitation programs should consider nutritional interventions after radiotherapy: Patients benefited from stabilized weights, improved nutritional status, and an improved quality of life. Physical exercise interventions demonstrated improvements in physical function, muscular endurance, range of motion, overall quality of life, and showed reductions in pain, and fatigue.

Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review.

Background: Despite advances in behavioral and pharmacotherapy interventions, substance use disorders (SUDs) are frequently refractory to treatment. Glutamatergic dysregulation has received increasing attention as one common neuropathology across multiple substances of abuse. Ketamine is a potent N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist which has been found to be effective in the treatment of severe depression. Here we review the literature on the efficacy of ketamine in the treatment of SUDs. Methods: A systematic review of the PubMed, Scopus, and ClinicalTrials.gov databases was undertaken to identify completed and ongoing human studies of the effectiveness of ketamine in the treatment of SUDs between January 1997 and January 2018. Results and conclusion: Seven completed studies were identified. Two studies focused on alcohol use disorder, two focused on cocaine use disorder, and three focused on opioid use disorder. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates, although studies were limited by small sample sizes, a homogeneous population and short follow-up. Studies of alcohol and opioid use disorders found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion, although these were not placebo-controlled trials. These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment. We conclude with an overview of the six ongoing studies of ketamine in the treatment of alcohol, cocaine, cannabis, and opioid use disorders and discuss future directions in this emerging area of research.

Patterns, perceptions, and perceived barriers to physical activity in adult cancer survivors.

PURPOSE: Physical activity (PA) during and after cancer treatment is associated with improved cancer- and non-cancer-related outcomes. We assessed for predictors of change in PA levels among cancer survivors. METHODS: Adult cancer survivors from a comprehensive cancer center completed a one-time questionnaire retrospectively assessing PA levels before, during, and after cancer treatment along with their perceptions of PA. Multivariable logistic regression models evaluated the association of clinico-demographics variables and perceptions of PA with changes in whether patients were meeting PA guidelines after cancer diagnosis. RESULTS: Among the 1003 patients, 319 (32%) met moderate to vigorous PA (MVPA) guidelines before diagnosis. Among those meeting guidelines before diagnosis, 50% still met guidelines after treatment; 12% not meeting MVPA guidelines initially met them after treatment/at follow-up. Among patients meeting guidelines before diagnosis, better ECOG performance status at follow-up, receiving curative therapy, and spending a longer time on PA initially were each associated with meeting guidelines at follow-up. After controlling for other variables, perceiving that PA improves quality of life (adjusted odds ratio, aOR = 11.09, 95%CI [1.42-86.64], P = 0.02) and overall survival (aOR = 8.52, 95%CI [1.12-64.71], P = 0.04) was each associated with meeting MVPA guidelines during/after treatment, in patients who did not meet guidelines initially. Only 13% reported receiving counseling, which was not associated with PA levels. Common reported barriers to PA included fatigue, lacking motivation, and being too busy. CONCLUSIONS: Patient perceptions of PA benefits are strongly associated with improving PA levels after a cancer diagnosis. Clinician counseling should focus on patient education and changing patient perceptions.

High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high-dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults. MATERIALS AND METHODS: Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double-blind, randomized, placebo-controlled trial of high-dose vitamin D3 (D3 ) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3 , or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3 , respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed-effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time. RESULTS: At enrollment, >75% of participants in all groups had plasma 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000-IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000-IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000-IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000-IU D3 group. CONCLUSION: In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high-dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.

Behavioral Treatments for Alcohol Use Disorder and Post-Traumatic Stress Disorder.

Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are highly prevalent and debilitating psychiatric conditions that commonly co-occur. Individuals with comorbid AUD and PTSD incur heightened risk for other psychiatric problems (e.g., depression and anxiety), impaired vocational and social functioning, and poor treatment outcomes. This review describes evidence-supported behavioral interventions for treating AUD alone, PTSD alone, and comorbid AUD and PTSD. Evidence-based behavioral interventions for AUD include relapse prevention, contingency management, motivational enhancement, couples therapy, 12-step facilitation, community reinforcement, and mindfulness. Evidence-based PTSD interventions include prolonged exposure therapy, cognitive processing therapy, eye movement desensitization and reprocessing, psychotherapy incorporating narrative exposure, and present-centered therapy. The differing theories behind sequential versus integrated treatment of comorbid AUD and PTSD are presented, as is evidence supporting the use of integrated treatment models. Future research on this complex, dual-diagnosis population is necessary to improve understanding of how individual characteristics, such as gender and treatment goals, affect treatment outcome.

A Descriptive Analysis of the Educational Perceptions, Professional Identity, and Professional Practices of Dual-Trained Music Therapists as Counselors.

BACKGROUND: Given the rise in music therapy master's programs that offer dual degrees in music therapy and counseling or programs that satisfy state mental health counseling licensure laws, the professional counseling field is playing an increased role in the advanced education and professional practices of music therapists. OBJECTIVE: To identify factors that lead music therapists to pursue advanced education with an emphasis in professional counseling, perceptions about benefits and drawbacks for three advanced degree options (i.e., music therapy, counseling, and music therapy/counseling dual degree), and describe the professional practices and identity of dual-trained music therapists as counselors. METHODS: A convenience sample of music therapists (n = 123) who held board certification, and held a master's degree or higher that emphasized professional counseling, completed an online survey. We used descriptive statistics to analyze categorical and numeric survey data. RESULTS: Eligibility for licensure as a professional counselor was the most important decisional factor in selecting a specific master's degree program. Respondents also reported favorable perceptions of the dual degree in music therapy and counseling. With regard to professional practice and identity, respondents reported high use of verbal processing techniques alongside music therapy interventions, and dual-trained music therapists retained their professional identity as a music therapist. CONCLUSIONS: The reported view of licensure in a related field as beneficial and frequent use of verbal processing techniques warrants future study into the role of counseling in the advanced training of music therapists. Given contradictory findings across studies, we recommend investigators also explore how a degree in a related field affects career longevity of music therapists.

Influence of Flaxseed Lignan Supplementation to Older Adults on Biochemical and Functional Outcome Measures of Inflammation.

Evidence from the literature suggests that dietary flaxseed lignans have the ability to modulate inflammation, which is recognized as the underlying basis of multiple chronic human diseases in older adults. Our objective was to determine the effects of oral lignan supplementation on biochemical and functional indicators of inflammation as well as safety and tolerability in older healthy adults. We designed a randomized, double-blind, placebo-controlled clinical trial in older healthy adults (60-80 years) to assess flaxseed lignan-enriched complex (∼38% secoisolariciresinol diglucoside [SDG]; 600 mg SDG dose) oral supplementation effects on biochemical and functional indicators of inflammation and safety and tolerability in older healthy adults after 6 months of once-daily oral administration. The clinical trial confirmed that plasma concentration of total flaxseed lignans (free and conjugated forms) secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (ENL) were significantly associated with daily oral supplementation of flaxseed lignan-enriched complex (p < 0.05). A significant decrease in systolic blood pressure (SBP; from a mean of 155 ± 13 mm Hg at baseline to 140 ± 11 mm Hg at 24 weeks) was observed in lignan-supplemented participants stratified into an SBP ≥140 mm Hg subcategory (p = 0.04). No differences were found between treatment or placebo groups in terms of cognition, pain, activity, physical measurements (calf, waist, and upper arm circumstances), and grip strength. With respect to blood inflammatory markers, lipid profiles, and biochemical parameters, no significant differences were found between treatment and placebo groups at the end of the 6-month supplementation. No adverse effects were reported during supplementation. These data further support the safety and tolerability of long-term flaxseed lignan-enriched complex supplementation in older adults and identify an ability to favorably modulate SBP, an important risk factor in cardiovascular disease.

Protocol for the MATCH study (Mindfulness and Tai Chi for cancer health): A preference-based multi-site randomized comparative effectiveness trial (CET) of Mindfulness-Based Cancer Recovery (MBCR) vs. Tai Chi/Qigong (TCQ) for cancer survivors.

PURPOSE: A growing number of cancer survivors suffer high levels of distress, depression and stress, as well as sleep disturbance, pain and fatigue. Two different mind-body interventions helpful for treating these problems are Mindfulness-Based Cancer Recovery (MBCR) and Tai Chi/Qigong (TCQ). However, while both interventions show efficacy compared to usual care, they have never been evaluated in the same study or directly compared. This study will be the first to incorporate innovative design features including patient choice while evaluating two interventions to treat distressed cancer survivors. It will also allow for secondary analyses of which program best targets specific symptoms in particular groups of survivors, based on preferences and baseline characteristics. METHODS AND SIGNIFICANCE: The design is a preference-based multi-site randomized comparative effectiveness trial. Participants (N=600) with a preference for either MBCR or TCQ will receive their preferred intervention; while those without a preference will be randomized into either intervention. Further, within the preference and non-preference groups, participants will be randomized into immediate intervention or wait-list control. Total mood disturbance on the Profile of mood states (POMS) post-intervention is the primary outcome. Other measures taken pre- and post-intervention and at 6-month follow-up include quality of life, psychological functioning, cancer-related symptoms and physical functioning. Exploratory analyses investigate biomarkers (cortisol, cytokines, blood pressure/Heart Rate Variability, telomere length, gene expression), which may uncover potentially important effects on key biological regulatory and antineoplastic functions. Health economic measures will determine potential savings to the health system.

Impact of high-dose vitamin D3 on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults.

OBJECTIVES: High-dose vitamin D3 increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3 on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. METHODS: In a double blind, randomized controlled trial, critically ill ventilator-dependent adults (N = 30) received enteral vitamin D3 (250,000 or 500,000 IU total over 5 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. RESULTS: Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P < 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3 dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). CONCLUSIONS: The present study found a dose-related increase in plasma free-25(OH)D levels, which was associated with increasing circulating mRNA expression of hCAP18 over time. There were no correlations between changes in total and free 25(OH)D against plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3 administration on endogenous AMPs.

Protocol for a 24-Week Randomized Controlled Study of Once-Daily Oral Dose of Flax Lignan to Healthy Older Adults.

BACKGROUND: Increased oxidative stress and inflammation are associated with aging, and contribute to an increased risk of chronic disease in older adults. Flaxseed lignans demonstrate antioxidant and anti-inflammatory activity, but their ability to reduce oxidative stress and inflammation markers in older adult populations has received limited investigation. OBJECTIVE: This is a chronic intervention trial of community-dwelling healthy older adults to examine the effects of a flaxseed lignan (secoisolariciresinol diglucoside; SDG) enriched supplement (BeneFlax) compared to a placebo. The primary aim was to demonstrate the safety of BeneFlax and confirm its anti-inflammatory efficacy on markers of oxidative stress and inflammation, and subsequent functional outcomes, including those associated with its anti-inflammatory efficacy. A secondary aim was to determine flaxseed lignan metabolite concentrations in blood. METHODS: A double-blind randomized clinical trial was conducted. Subjects were healthy community-dwelling adults aged 60-80 years. Testing was performed at baseline, 8, 16, and 24 weeks. The 24-week intervention consisted of 600 milligrams (mg) of SDG daily or an equivalent amount (volume) of placebo. All participants received 1000 international units of vitamin D to ensure adequate vitamin D status. Measurements consisted of blood pressure, hematology, and tolerability for safety assessments; blood oxidative stress and inflammatory biomarkers for efficacy; and cognition, muscle strength, and pain as functional outcomes. Secondary endpoints of plasma levels of lignan metabolites were analyzed by mass spectrometry. Other tests, such as bone turnover markers and fecal levels of flax cyclolinopeptides, will be performed at a later date. RESULTS: Thirty-two participants were recruited (19 intervention and 13 control) and all completed the trial. Numerous Health Canada-imposed exclusion criteria limited recruitment success. Analyses are ongoing, but the baseline data available for a number of parameters indicate no differences between treatment groups. Safety measures (vital signs) did not change from baseline and were not significantly different between treatment and placebo groups at 24 weeks. CONCLUSIONS: Preliminary results indicate that no safety concerns are associated with administering 600 mg SDG for 24 weeks to adults between the ages of 60 and 80 years. TRIAL REGISTRATION: Clinicaltrials.gov NCT01846117; https://clinicaltrials.gov/ct2/show/NCT01846117 (Archived by WebCite at http://www.webcitation.org/6nlDZNjmA).

Successful Treatment of Suspected Cannabinoid Hyperemesis Syndrome Using Haloperidol in the Outpatient Setting.

Chronic use of cannabis can result in a syndrome of hyperemesis characterized by cyclical vomiting without any other identifiable causes. Cannabinoid hyperemesis syndrome (CHS) is seldom responsive to traditional antiemetic therapies. Despite frequent nausea and vomiting, patients may be reluctant to discontinue use of cannabis. We report a case of severe, refractory CHS with complete resolution of nausea and vomiting after treatment with haloperidol in the outpatient setting. After review of the literature, we believe this is the first reported successful outpatient treatment of CHS and suggests a potential treatment for refractory patients.

High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial.

BACKGROUND: There is a high prevalence of vitamin D deficiency in the critically ill patient population. Several intensive care unit studies have demonstrated an association between vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) < 20 ng/mL] and increased hospital length of stay (LOS), readmission rate, sepsis and mortality. MATERIAL AND METHODS: Pilot, double blind randomized control trial conducted on mechanically ventilated adult ICU patients. Subjects were administered either placebo, 50,000 IU vitamin D3 or 100,000 IU vitamin D3 daily for 5 consecutive days enterally (total vitamin D3 dose = 250,000 IU or 500,000 IU, respectively). The primary outcome was plasma 25(OH)D concentration 7 days after oral administration of study drug. Secondary outcomes were plasma levels of the antimicrobial peptide cathelicidin (LL37), hospital LOS, SOFA score, duration of mechanical ventilation, hospital mortality, mortality at 12 weeks, and hospital acquired infection. RESULTS: A total of 31 subjects were enrolled with 13 (43%) being vitamin D deficient at entry (25(OH)D levels < 20 ng/mL). The 250,000 IU and 500,000 IU vitamin D3 regimens each resulted in a significant increase in mean plasma 25(OH)D concentrations from baseline to day 7; values rose to 45.7±19.6 ng/mL and 55.2 ± 14.4 ng/mL, respectively, compared to essentially no change in the placebo group (21±11.2 ng/mL), p<0.001. There was a significant decrease in hospital length of stay over time in the 250,000 IU and the 500,000 IU vitamin D3 group, compared to the placebo group (25 ± 14 and 18 ± 11 days compared to 36 ± 19 days, respectively; p=0.03). There was no statically significant change in plasma LL-37 concentrations or other clinical outcomes by group over time. CONCLUSIONS: In this pilot study, high-dose vitamin D3 safely increased plasma 25(OH)D concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01372995).