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Myristoylation, the N-terminal addition of the fatty acid myristate to proteins, regulates membrane-bound signal transduction pathways important in cancer cell biology. This modification is catalyzed by two N-myristoyltransferases, NMT1 and NMT2. Zelenirstat is a first-in-class potent oral small molecule inhibitor of both NMT1 and NMT2 proteins. Patients with advanced solid tumors and relapsed/refractory (R/R) B-cell lymphomas were enrolled in an open label, phase I dose escalation trial of oral daily zelenirstat, administered in 28-day cycles until progression or unacceptable toxicity. The endpoints were to evaluate dose-limiting toxicities (DLT) to establish a maximum tolerated dose (MTD), pharmacokinetic parameters, and anticancer activity. Twenty-nine patients were enrolled (25 advanced solid tumor; 4 R/R B-cell lymphoma) and 24 were DLT-evaluable. Dosing ranged from 20 mg once daily (OD) to 210 mg OD without DLT, but gastrointestinal DLTS were seen in the 280 mg cohort. MTD and recommended phase 2 dose were 210 mg OD. Common adverse events were predominantly Gr ≤ 2 nausea, vomiting, diarrhea, and fatigue. Plasma concentrations peaked at 2 h with terminal half-lives averaging 10 h. Steady state was achieved by day 15, and higher doses achieved trough concentrations predicted to be therapeutic. Stable disease as best response was seen in eight (28%) patients. Progression-free survival and overall survival were significantly better in patients receiving 210 mg OD compared to those receiving lower doses. Zelenirstat is well-tolerated, achieves plasma exposures expected for efficacy, and shows early signs of anticancer activity. Further clinical development of zelenirstat is warranted. [ABSTRACT FROM AUTHOR]

The article focuses on a case of a previously healthy, vaccinated 7-year-old experiencing occipital scalp and neck pain following a bicycle accident, later developing acute hearing loss and difficulty walking. Topics include the patient's clinical presentation, including neurological symptoms and abnormal laboratory findings, and diagnostic evaluations such as imaging and blood tests, leading to the diagnosis of a concussion and subsequent neurological complications.

Background: Chronic kidney disease (CKD) and kidney failure in childhood are associated with significant and life-altering morbidities and lower quality of life. Emerging evidence suggests that management should be guided in part by symptom burden; however, there is currently no standardized assessment tool for quantifying symptom burden in this pediatric population. This study aimed to develop and refine a patient-reported symptom assessment tool for children with CKD/kidney failure (PRO-Kid), to evaluate the frequency and impact of symptoms. Methods: This was a prospective observational study of children and caregivers of children with CKD/kidney failure at two Canadian pediatric care centers. Building on previously published patient-reported outcome measures (PROs) for the assessment of symptom burden in other populations, we drafted a 13-item questionnaire. Cognitive interviews were performed with children and caregivers of children with CKD/kidney failure to iteratively refine the questionnaire. Results: Twenty-four participants completed cognitive interviewing (11 children, 13 caregivers). The most common symptoms endorsed were feeling left out, feeling sad/depressed, inability to focus, tiredness, nausea, vomiting, not wanting to eat, and changes in the taste of food. Feeling left out was added to the questionnaire as almost all participants voiced this as a frequent and impactful symptom, resulting in a 14-item questionnaire. Conclusions: PRO-Kid is the first pediatric CKD/kidney failure-specific PRO tool to assess symptom burden. Future work should validate this tool in a larger cohort so that it may be used to improve the care of children living with CKD/kidney failure. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Cannabis can induce negative outcomes among consumers with mental health conditions. This study examined medical help-seeking behavior, patterns of adverse effects, and perceived impacts of cannabis among consumers with and without mental health conditions. Methods: Data came from the International Cannabis Policy Study, via online surveys conducted in 2018. Respondents included 6,413 past 12-month cannabis consumers aged 16–65, recruited from commercial panels in Canada and the US. Regression models examined differences in adverse health effects and perceived impact of cannabis among those with and without self-reported past 12-month experience of anxiety, depression, PTSD, bipolar disorder, psychosis. Results: Overall, 7% of past 12-month consumers reported seeking medical help for adverse effects of cannabis, including panic, dizziness, nausea. Help-seeking was greater for those with psychosis (13.8%: AOR = 1.78; 1.11–2.87), depression (8.9%: AOR = 1.57; 1.28–1.93), and bipolar disorder (10.1%: AOR = 1.53; 1.44–2.74). Additionally, 54.1% reported using cannabis to manage symptoms of mental health, with higher rates among those with bipolar (90.8%) and PTSD (90.7%). Consumers reporting >1 condition were more likely to perceive positive impacts on friendships, physical/mental health, family life, work, studies, quality of life (all p <.001). Consumers with psychosis were most likely to perceive negative effects across categories. Conclusion: For conditions with substantial evidence suggesting cannabis is harmful, greater help-seeking behaviors and self-perceived negative effects were observed. Consumers with mental health conditions generally perceive cannabis to have a positive impact on their lives. The relationship between cannabis and mental health is disorder specific and may include a combination of perceived benefits and harms. [ABSTRACT FROM AUTHOR]

Purpose: Initial investigation of the impact of a Cancer Survivorship Clinic following its introduction in February 2017.Methods: A systematic chart review of 176 patients enrolled in the Cancer Survivorship Clinic (CSC) who completed a minimum of one follow-up visit after the initial baseline visit. This was assessed using three screening tools: distress thermometer (DT), Canadian Problem Checklist (CPC), and Edmonton Symptom Assessment Scale (ESAS). Descriptive statistics and t tests were utilized to assess the impact of the CSC.Results: Distress thermometer: Statistically significant decline in scores from the baseline visit to the follow-up visit among the study population (p < 0.05). There was a significant decline in score among high-risk patients with an initial DT≥4 (p < 0.0001). Canadian Problem Checklist: Based on the initial baseline visit, the top five reported causes of distress among the study population include pain, anxiety, fatigue, tingling in hands and feet, sleep. Edmonton Symptom Assessment Scale: Statistically significant decline in reported pain, tiredness, nausea, depression, anxiety, drowsiness, and shortness of breath scores (p < 0.05).Conclusions: Overall, patients had a significant reduction in distress from the baseline visit to the follow-up visit. High-risk patients experienced a more significant reduction in distress. Reduction in patient distress was independent of the number of visits to the clinic. Reported symptom severity for pain, tiredness, depression, anxiety, drowsiness, and shortness of breath also declined significantly following clinic intervention. Further qualitative studies required to establish the clinical significance of study findings.Implications For Cancer Survivors: Continued active clinical support and education for cancer survivors should be considered a potentially essential element in the cancer treatment trajectory to address patient well-being and distress. [ABSTRACT FROM AUTHOR]

Background and aims: Varenicline effectiveness may be related to the level of adherence, which might be reduced by adverse effects such as nausea. The aim of the study was to test a possible effect of nausea on smoking cessation outcomes mediated by adherence. Design Mediation path analysis. Setting: Multiple sites within Canada and the United States. Participants: Treatment‐seeking smokers receiving varenicline from two smoking cessation clinical trials: Quit2Live (NCT01836276; n = 449) and Pharmacogenetics of Nicotine Addiction Treatment (PNAT) (NCT01314001; n = 421). Measurements Nausea severity was collected through self‐report and adherence was biologically assessed using varenicline concentrations (Quit2Live, plasma sample at week 4; PNAT, saliva sample at week 2). In Quit2Live, the end‐points were cotinine‐verified abstinence at weeks 4, 12 and 26. In PNAT, the end‐points were carbon monoxide‐verified abstinence at weeks 2, 12 and 26. Findings Early nausea was not directly associated with abstinence [odds ratio (OR) ranging from 0.73–1.28; P ≥ 0.26]. However early nausea was indirectly associated with lower cessation rates at multiple timepoints (ORs ranging from 0.92–0.94; 95% CI between 0.83–0.99) in a relationship mediated by reduced varenicline adherence (assessed by plasma varenicline concentrations) in the primary trial (Quit2Live). This relationship between nausea, adherence and cessation was similar in direction but weaker in effect size (ORs ranging from 0.98–0.99; 95% CI between 0.90–1.03) in a secondary trial (PNAT), where adherence was assessed using salivary varenicline concentrations. Conclusions: These data suggest that early nausea during varenicline treatment may be indirectly associated with lower likelihood of smoking cessation through reducing varenicline adherence. Differences in robustness between the trials may be due to the different biological matrices (plasma vs. saliva) and/or timing used to assess varenicline adherence. The results of the first study suggest that improved management of early nausea during varenicline treatment may positively impact smoking cessation success through increasing varenicline adherence. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the administration of oral cannabis extracts to pediatric patients in palliative care. Topics explored include the selection of patients with life-limiting or terminal illnesses that would receive medical cannabinoids, the observed improvement in the symptoms reported such as pain and nausea, and the importance of compliance to medical guidance to prevent cases of cannabis overdoses.

Complementary and alternative medicine has been shown to be beneficial in reducing chemotherapy-induced nausea and vomiting. However, conclusive results are lacking in order to confirm its usefulness. The purpose of this study was to determine whether a standardized yoga intervention could reduce these adverse symptoms. This was a partially randomized and blinded controlled trial comparing a standardized yoga intervention with standard care. Eligible patients were adults diagnosed with stages I to III breast cancer receiving chemotherapy. Patients randomized to the experimental group participated in an 8-week yoga program. There was no significant difference between the experimental and control groups on chemotherapy-induced nausea and vomiting after 8 weeks. Results suggest the yoga program is not beneficial in managing these adverse symptoms. However, considering preliminary evidence suggesting yoga’s beneficial impact in cancer symptom management, methodological limitations should be explored and additional studies should be conducted. [ABSTRACT FROM AUTHOR]

Aim: Given the ubiquitous nature of hangover experience among drinkers, this study aimed to profile hangover experience in terms of the number and patterns of past year symptoms.Methods: Current drinkers in Canada (n = 565) recruited through zoompanel were asked about 13 past year hangover symptoms. These were explored through correlation with alcohol consumption, problems, treatment and other factors.Findings: Increased number of symptoms were associated with higher Alcohol Use Disorders Identification Test (AUDIT) problem score, perceived harm from drinking, younger age and flushing/blushing when drinking (Mean = 3.3 symptoms). Four patterns were found from latent class analysis; class 4 (43%) no symptoms; class 3 (13%) thirst, tiredness, headache, nausea and vomiting; class 2 (22%) thirst, tiredness and headache; and class 1 (21%) wide range. Class 1 was characterised by blushing when drinking, higher perceived harm and attempts to reduce drinking due to hangovers. Classes 1–3 were associated with heavier consumption; only class 3 compared with class 4 had lower drinking refusal self-efficacy. Conclusions: higher alcohol consumption and lower drinking refusal self-efficacy relate to more symptoms; however, a group with variable alcohol consumption did not experience hangovers. The link between problems, treatment and hangover was not clear from patterns of symptoms; symptom severity may be worth further investigation. [ABSTRACT FROM PUBLISHER]

Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine ( P < .05). As well, doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores. [ABSTRACT FROM AUTHOR]

Although bendamustine has been used to treat lym-phoproliferative disorders for decades, it has only recently been approved for use in Canada. Thus, Canadian recommendations on the administration of bendamustine and the management of common adverse events (AEs) are needed. This article highlights effective management and assessment strategies recommended by Canadian nurses and pharmacists for the most common AES arising from the use of bendamustine in patients with chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Those strategies include administering bendamustine over 60 minutes instead of 30 minutes, administering pre-medications to control infusion-related reactions and nausea, hydrating patients to minimize fatigue, and using free-flowing saline at the closest port to prevent phlebitis. [ABSTRACT FROM AUTHOR]

Aim Nabilone is a synthetic cannabinoid prescription drug approved in Canada since 1981 to treat chemotherapy-induced nausea and vomiting. In recent years, off-label use of nabilone for chronic pain management has increased, and physicians have begun to express concerns about nabilone becoming a drug of abuse. This study evaluates the evidence for abuse of nabilone, which is currently ill-defined. Study design Scientific literature, popular press and internet databases were searched extensively for evidence of nabilone abuse. Focused interviews with medical professionals and law enforcement agencies across Canada were also conducted. Findings The scientific literature and popular press reviews found very little reference to nabilone abuse. Nabilone is perceived to produce more undesirable side effects, to have a longer onset of action and to be more expensive than smoked cannabis. The internet review revealed rare and isolated instances of recreational use of nabilone. The database review yielded little evidence of nabilone abuse, although nabilone seizures and thefts have occurred in Canada in the past few years, especially in Ontario. Most law enforcement officers reported no instances of nabilone abuse or diversion, and the drug has no known street value. Medical professionals reported that nabilone is not perceived to be a matter of concern with respect to its abuse potential. Conclusions Reports of nabilone abuse are extremely rare. However, follow-up of patients using nabilone for therapeutic purposes is prudent and should include assessment of tolerance and dependence. Prospective studies are also needed to definitively address the issue of nabilone abuse. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Hyperemesis gravidarum (HG) is the second most common reason for hospitalisation during pregnancy. Since 2002, a new HG treatment protocol consisting of metoclopramide plus diphenhydramine was put in place at CHU Sainte-Justine, affiliated to University of Montreal, Quebec, Canada. The objectives of this study were to evaluate the effectiveness of this new HG protocol regarding length of hospitalisation for HG, rate of rehospitalisation, evolution of nausea and vomiting symptoms, and rate of adverse events. Study design: A retrospective cohort study was conducted from 2002 to 2006 on the population of pregnant women diagnosed with HG, and treated at CHU Sainte-Justine with the new protocol consisting of intravenous metoclopramide 1.2–1.8mg/h plus diphenhydramine 50mg every 6h. These women were compared to a historical control group consisting of women diagnosed with HG, and treated in the same institution with intravenous droperidol 0.5–1mg/h plus diphenhydramine 25–50mg every 6h between 1998 and 2001. Results: During the study period, a total of 130 pregnant women were exposed to the new HG protocol versus 99 that were exposed to the droperidol and diphenhydramine combination between 1998 and 2001. Our study showed that the new HG protocol was associated with a greater improvement of vomiting symptoms (36% vs. 21%; p =0.0397), and with fewer adverse events. The new HG protocol was equivalent to the droperidol and diphenhydramine combination to reduce nausea symptoms, length of hospitalisation (3.7 days vs. 3.1 days), and rate of rehospitalisation for HG (19.23% vs. 24.44%). Conclusions: The new protocol consisting of the combination of metoclopramide and diphenhydramine appears to be a good option in the management of hyperemesis gravidarum. [Copyright &y& Elsevier]

bourbonnais f.f., perreault a. & bouvette m. (2004) Journal of Nursing Management 12, 194–200 Introduction of a pain and symptom assessment tool in the clinical setting – lessons learned It has long been acknowledged that pain is a subjective, multifaceted phenomenon which is influenced by many factors such as past experience and culture. However there are other symptoms that can be distressing such as dyspnea and nausea. In Ottawa, Canada there was recognition that inconsistencies existed in pain and symptom assessment methods and documentation in the different institutions and agencies when patients with cancer moved from one setting to another as their illness progressed. Therefore, a working group with clinical representatives was formed with a mandate to develop a standardized tool so that there would be a common language for pain and symptom assessment. Although various tools have been developed for pain assessment such as visual analogue or numeric rating scales, there has been limited attention focused on the sustainability of these tools in the practice setting. This paper will focus on the importance of the use of tools for pain and symptom management, issues around implementing them, and sustaining their use in the clinical setting. The Ottawa Pain and Symptom Assessment Record will be used as an exemplar. [ABSTRACT FROM AUTHOR]

The article presents information about antiemetic guidelines for Hamilton Regional Cancer Center. The Hamilton Regional Cancer Center (HRCC) and its host hospital, the Hamilton Health Sciences Corp. (HHSC), is currently the second largest hospital system in Canada. It is attempting to negotiate consistent guidelines across three sites, a process that has been hampered by the recent hospital restructuring process. The HRCC has a Formulary and Therapeutics Committee, which reports to the Systemic Treatment Program. The HRCC uses the working definitions of chemotherapy emetogenicity from the antiemetic trials of the National Cancer Institute of Canada, generated over the past several years.

Medical cannabis access has been legalized in more than 30 countries worldwide and popularity among patients is increasing rapidly. Cannabinoid-based treatments have been shown to be beneficial for several symptoms such as chemotherapy-induced nausea and vomiting, spasticity, chronic pain, intractable seizures and insomnia, yet high-quality clinical trials are still limited. As millions of patients now have legal access to medical cannabis, little information is available about the development of best clinical practices and an effective medical cannabis clinic model. A medical cannabis clinic is an innovative and emergent practice model that may be necessary to bridge the gap between patient and healthcare provider interest and existing barriers to the prescription of medical cannabis treatments, such as limited medical education, lack of high-quality clinical research and challenging or evolving regulatory frameworks. In this paper, we describe the model of care and organization of a dedicated medical cannabis clinic operating in Quebec, Canada since 2014. We share the principles of medical cannabis practice, including the structure of its medical and support team, clinic organisation and procedure guidelines. Key clinic statistics and patient demographics are shared with year by year comparison. Operating since 2014, the clinic has endured a rapidly changing regulatory landscape in Canada, overcoming numerous challenges including medical and social stigma, limited funding, resources and institutional support combined with a high demand for services. To support medical cannabis leaders globally, an important knowledge-sharing is required. The clinic has expanded to a network of four clinic sites across Quebec and offers continuing education and preceptorships to health care providers and trainees as well as research services to both academic and industry partners. The description of the clinic offers guidance on medical cannabis treatment and care and discusses possible solutions to associated challenges. The clinic model of care can be adapted to different healthcare settings and regulatory frameworks; it may assist physicians and health care providers in the development of medical cannabis clinics or the implementation of best practices as medical cannabis access continues to evolve., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: With legal access to medical cannabis in Canada since 2001, there is a need to fully characterize its use at both the individual and population levels. We draw on data from Canada's largest cohort study of medical cannabis to identify the primary reasons for medical cannabis authorization in Canada from 2014 to 2019 in two major provinces: Alberta (AB) and Ontario (ON), and review the extent that evidence supports each indication., Methods: Self-reported baseline assessments were collected from adult patients in ON (n = 61,835) and AB (n = 3410) who were authorized medical cannabis. At baseline, sociodemographic, primary medical information, and validated clinical questionnaires were completed by patients as part of an individual assessment. Patients' reasons for seeking medical cannabis were compared to published reviews and guidelines to assess the level of evidence supporting medical cannabis use for each condition., Results: Medical cannabis use in both AB and ON was similar in both demographic and reason for authorization. The most common reasons for medical cannabis authorization were: (1) pain (AB = 77%, ON = 76%) primarily due to chronic musculoskeletal, arthritic, and neuropathic pain, (2) mental health concerns (AB = 32.9%, ON = 38.7%) due to anxiety and depression, and (3) sleep problems (AB = 28%, ON = 25%). More than 50 other conditions were identified as reasons for obtaining authorization., Conclusion: In both AB and ON, the majority of reasons for medical cannabis authorization are not substantiated by clinical evidence to fully support its efficacy for long-term use. Ongoing epidemiological studies on medical cannabis on these treatments are warranted to fully outline its treatment benefits or risks.

Background: Chemotherapy-induced nausea and vomiting (CINV) impacts quality of life for patients. Guidelines for emetogenicity classification and prevention of CINV in children were recently published and endorsed by pediatric oncology organizations., Procedure: A multicenter chart review was performed at four Canadian pediatric oncology centers examining rates of prescribing adherence to CINV guidelines between January 2012 and December 2015. Eligible patients received their first chemotherapy course of highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC)., Results: Guideline adherence was described in 204 patients as antiemetic-only guideline adherence (AGA; examined medication/class prescribed only) and complete guideline adherence (CGA; examined medication/class, dose, frequency, and duration prescribed). Adherence was 29% (HEC 30%, MEC 19%, P = 0.1) and 2% for AGA and CGA patients, respectively. Vomiting in the first 24 h was experienced by 24% of AGA and 34% of non-AGA patients (P = 0.13), with mean breakthrough medication doses similar between AGA and non-AGA groups (HEC 1.8 vs 1.5, P = 0.45; MEC 3 vs 1.42, P = 0.35). In the first 24 h, HEC AGA patients achieved a complete control rate of 37% vs 45% for non-AGA patients (P = 0.31), while patients receiving AGA therapy for MEC achieved a complete control rate of 80% vs 24% for non-AGA patients (P = 0.02)., Conclusions: Adherence to guidelines was low across all four pediatric institutions. Each center used different approaches to implement pediatric CINV guidelines. Complete CINV control was low, with reports of emesis high, indicating that patients are not receiving optimal treatment., (© 2018 Wiley Periodicals, Inc.)

The dangers to the fetus of using marijuana to treat morning sickness, Canada's plans to regulate 'vaping' to protect teens from nicotine, The search for therapies that prevent PTSD in children [ABSTRACT FROM AUTHOR]

Background: The amyloid-beta peptide Abeta(42) has been implicated in the pathogenesis of Alzheimer's disease (AD). We aimed to test the effects of tarenflurbil, a selective Abeta(42)-lowering agent (SALA), on cognition and function in patients with mild to moderate AD. Methods: 210 patients living in the community who had a mini-mental state examination (MMSE) score of 15-26 were randomly assigned to receive tarenflurbil twice per day (400 mg [n=69] or 800 mg [n=70]) or placebo (n=71) for 12 months in a phase II, multicentre, double-blind study. Primary efficacy outcomes were the AD assessment scale cognitive subscale (ADAS-cog), the Alzheimer's Disease Cooperative Study activities of daily living scale (ADCS-ADL), and the clinical dementia rating sum of boxes (CDR-sb). In a 12-month extended treatment phase, patients who had received tarenflurbil continued to receive the same dose, and patients who had received placebo were randomly assigned to tarenflurbil at 800 mg or 400 mg twice per day. Primary efficacy analyses were done by intention to treat. This trial is registered with Health Canada (084527) and the Medicines and Healthcare products Regulatory Agency in the UK (20365/0001/A 69316). Findings: A prespecified interaction analysis revealed that patients with mild AD (baseline MMSE 20-26) and moderate AD (baseline MMSE 15-19) responded differently to tarenflurbil in the ADAS-cog and the ADCS-ADL (p>or=0.10); therefore, these groups were analysed separately. Patients with mild AD in the 800 mg tarenflurbil group had lower rates of decline than did those in the placebo group in activities of daily living (ADCS-ADL difference in slope 3.98 [95% CI 0.33 to 7.62] points per year, effect size [reduction from placebo decline rate] 46.4%, Cohen's d 0.45; p=0.033) and global function (CDR-sb difference -0.80 [-1.57 to -0.03] points per year, effect size 35.7%, Cohen's d 0.42; p=0.042); slowing of cognitive decline did not differ significantly (ADAS-cog difference -1.36 [-4.07 to 1.36] points per year, effect size 33.7%, Cohen's d 0.20; p=0.327). In patients with moderate AD, 800 mg tarenflurbil twice per day had no significant effects on ADCS-ADL and ADAS-cog and had a negative effect on CDR-sb (-52%, Cohen's d -1.08; p=0.003). The most common adverse events were diarrhoea (in seven, nine, and five patients in the 800 mg, 400 mg, and placebo groups, respectively), nausea (in seven, seven, and four patients), and dizziness (in five, nine, and four patients). Patients with mild AD who were in the 800 mg tarenflurbil group for 24 months had lower rates of decline for all three primary outcomes than did patients who were in the placebo group for months 0-12 and a tarenflurbil group for months 12-24 (all p<0.001), and had better outcomes than did patients who were in the placebo group for months 0-12 and the 800 mg tarenflurbil group for months 12-24 (all p<0.05). Interpretation: 800 mg tarenflurbil twice per day was well tolerated for up to 24 months of treatment, with evidence of a dose-related effect on measures of daily activities and global function in patients with mild AD. Funding: Myriad Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Objectives: This study tested whether mothers with maternal hypothyroidism have increased odds of CHD in their offspring, and examined the relationship between CHD, maternal thyroid function, and nausea and vomiting in pregnancy., Background: Maternal hypothyroidism increases the risk for foetal demise and prematurity and can have a negative impact on neurodevelopment. Prior studies have postulated a relationship between maternal thyroid function, CHD, and maternal nausea and vomiting in pregnancy., Methods: A cross-sectional case-control study was conducted over a 17-month period to obtain a history of maternal thyroid status and nausea and vomiting in pregnancy. Paediatric echocardiograms were evaluated for CHD by a blinded paediatric cardiologist. Logistic regression analysis was performed to examine the association between CHD and maternal hypothyroidism., Results: Of the 998 maternal-child pairs, 10% (98/998) of the mothers reported a history of prenatal hypothyroidism. The overall prevalence of CHD in the study sample was 63% (630/998). Mothers with a history of hypothyroidism were significantly more likely to have offspring with CHD compared with mothers without a history of hypothyroidism (72 versus 62%; p=0.04). The adjusted odds ratio (95% confidence interval) of CHD in offspring associated with reported maternal hypothyroidism was 1.68 (1.02-2.78)., Conclusion: This study suggests that maternal hypothyroidism is a risk factor for the development of CHD. Further prospective investigations are necessary to confirm this association and delineate pathogenic mechanisms.

Objectives. This article will address the process involved in the development and implementation of a clinician-driven portable electronic chart on an Acute Pain Management Service (APMS). We describe the latest version of the program and provide 1 year of clinical data. Setting. Tertiary care center in Kingston, Ontario, Canada. Patients. All patients admitted to the APMS between August 1, 2005, and July 31, 2006. Results. A total of 8,726 APMS visits were made to 2,528 patients. Mean length of stay on the Service was 2.3 days. Sixty-one percent of patients reported an active pain score >3/10. Pain scores were highest with hip or knee surgery. Thirty-five percent of patients reported nausea. Conclusions. Executive sponsorship, alignment with institutional priorities, and user input are essential to the development, implementation, adoption, and sustainability of an electronic patient record. Ready access to data at the bedside can improve quality of care, while ongoing, comprehensive data can contribute to Phase IV drug trials. Incorporating both clinical and research outcomes in the database improves data quality and usability, but must be balanced with the impact of clinical time constraints on documentation. Wireless technology and Tablet computers provide portability and adequate screen size for documentation and reviewing of patient data on an acute pain service. It is necessary to provide solutions to process issues, such as printing electronic records during the transition from paper to electronic records. [ABSTRACT FROM AUTHOR]