A brief eHealth tool delivered in primary care to help parents prevent childhood obesity: a randomized controlled trial.

OBJECTIVES: To determine the feasibility and preliminary impact of an electronic health (eHealth) screening, brief intervention and referral to treatment (SBIRT) delivered in primary care to help parents prevent childhood obesity. METHODS: Parents of children (5-17 years) were recruited from a primary care clinic. Children's measured height and weight were entered into the SBIRT on a study-designated tablet. The SBIRT screened for children's weight status, block randomized parents to one of four brief interventions or an eHealth control and provided parents with a menu of optional obesity prevention resources. Feasibility was determined by parents' interest in, and uptake of, the SBIRT. Preliminary impact was based on parents' concern about children's weight status and intention to change lifestyle behaviours post-SBIRT. RESULTS: Parents (n = 226) of children (9.9 ± 3.4 years) were primarily biological mothers (87.6%) and Caucasian (70.4%). The proportion of participants recruited (84.3%) along with parents who selected optional resources within the SBIRT (85.8%) supported feasibility. Secondary outcomes did not vary across groups, but non-Caucasian parents classified as inaccurate estimators of children's weight status reported higher levels of concern and intention to change post-SBIRT. CONCLUSIONS: Our innovative, eHealth SBIRT was feasible in primary care and has the potential to encourage parents of unhealthy weight children towards preventative action.

5As Team obesity intervention in primary care: development and evaluation of shared decision-making weight management tools.

Despite several clinical practice guidelines, there remains a considerable gap in prevention and management of obesity in primary care. To address the need for changing provider behaviour, a randomized controlled trial with convergent mixed method evaluation, the 5As Team (5AsT) study, was conducted. As part of the 5AsT intervention, the 5AsT tool kit was developed. This paper describes the development process and evaluation of these tools. Tools were co-developed by the multidisciplinary research team and the 5AsT, which included registered nurses/nurse practitioners (n = 15), mental health workers (n = 7) and registered dieticians (n = 7), who were previously randomized to the 5AsT intervention group at a primary care network in Edmonton, Alberta, Canada. The 5AsT tool development occurred through a practice/implementation-oriented, need-based, iterative process during learning collaborative sessions of the 5AsT intervention. Feedback during tool development was received through field notes and final provider evaluation was carried out through anonymous questionnaires. Twelve tools were co-developed with 5AsT. All tools were evaluated as either 'most useful' or 'moderately useful' in primary care practice by the 5AsT. Four key findings during 5AsT tool development were the need for: tools that were adaptive, tools to facilitate interdisciplinary practice, tools to help patients understand realistic expectations for weight loss and shared decision-making tools for goal setting and relapse prevention. The 5AsT tools are primary care tools which extend the utility of the 5As of obesity management framework in clinical practice.

Samvisterin, a new natural antiplasmodial betulin derivative from Uapaca paludosa (Euphorbiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Uapaca paludosa is used in African traditional medicine for the treatment of malaria. MATERIALS AND METHODS: A bioguided fractionation of U. paludosa trunk bark extracts was performed on the basis of their antiplasmodial activity against Plasmodium falciparum. RESULTS: A new natural betulin derivative named samvisterin (2) was isolated. In addition, 12 already known compounds were isolated from U. paludosa and tested against P. falciparum: squalene (1); lupeol (3), betulonic acid methyl ester (4), ß-sitosterol (5), stigmasterol (6), betulin (7), betulinic acid (8), pentadecanoic acid (9), palmitic acid (10), margaric acid (11), stearic acid (12), methyl palmitate (13). With the exception of betulinic acid, all were isolated for the first time from U. paludosa. Their chemical structures were established on the basis of spectroscopic analysis. The antiplasmodial activity of compounds 1-8 was confirmed on the chloroquine-resistant strain of P. falciparum, FcM29-Cameroon, with IC50 values ranging from 0.7µg/ml (for 1) to 30µg/mL (for 3). The cytotoxicity of the fractions and isolated compounds was also determined on KB and Vero cell lines in order to determine the cytotoxicity/activity ratio of each one. CONCLUSIONS: The results obtained with samvisterin (2) show that this new compound is the most promising of the series, with a weak cytotoxicity leading to the best selectivity index values.

Effect of postnatal intermittent hypoxia on growth and cardiovascular regulation of rat pups.

BACKGROUND: Intermittent hypoxic episodes are common among preterm infants, although longer term consequences on growth pattern and cardiovascular regulation are unclear. Furthermore, the effects of intermittent hypoxia (IH) may depend on the pattern of hypoxia-reoxygenation. OBJECTIVES: We tested the hypothesis that a clustered versus dispersed pattern of repetitive IH during early postnatal life would induce differential long-term alteration in growth and cardiovascular regulation. METHODS: Sprague-Dawley rat pups were exposed to room air or to one of two patterns of IH (clustered vs. dispersed) from 1 to 7 days of life. Body weight was measured daily for the first 8 days and weekly from weeks 2 to 8. Blood pressure (BP) and heart rate were measured weekly from weeks 4 to 8 using a noninvasive tail-cuff method for awake, nonanesthetized animals. RESULTS: Exposure to both patterns of repetitive IH induced early growth restriction followed by later catch-up of growth to controls 3 weeks after completion of IH exposures. IH-exposed rats exhibited a sustained decrease in heart rate regardless of the hypoxic exposure paradigm employed. In contrast, a differential response was seen for arterial pressure; the clustered paradigm was associated with a significantly lower BP versus controls, while the pups exposed to the dispersed paradigm showed no effect on BP. CONCLUSION: We speculate that repetitive IH during a critical developmental window and regardless of IH exposure paradigm contributes to prolonged changes in sympathovagal balance of cardiovascular regulation.

Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline.

Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted) attributable to emphysema and documented A1AT deficiency (level ≤11 µmol/L) who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation) because of benefits in computed tomography scan lung density and mortality.

The effect of sterilisation on the light intensity of the reusable Trachlight™.

We examined the light intensity delivered by the Trachlight™ reusable lightwand and the effect of repeated sterilisation on this light intensity. Using a light meter and test chamber, the light intensity of 12 new Trachlights and 31 Trachlights available in operating theatres was measured. In addition, five new devices underwent 30 repeated sterilisations with light intensity measurement after each cleaning. There was no difference between the light intensity of new Trachlights (median (IQR [range]) 2282 (2202-2780 [1970-4400])) lux and the devices currently in service (2295 (2018-2796 [1649-3280]) lux (p = 0.27)). The median (range) number of uses for devices currently in service was only 3 (0-9). There was, however, significant light intensity loss after 10, 20 and 30 cleanings (p = 0.001). After 10 cleanings, the mean light intensity was 75% of initial output, and after 30 cycles, light intensity was 59% of initial output.

A qualitative study to identify factors influencing COXIB prescribed by family physicians for musculoskeletal disorders.

INTRODUCTION: Cyclo-oxygenase-2 inhibiting (COXIB) anti-inflammatories have been the drug class prescribed for a large number of cases of musculoskeletal (MSK) disorders in Canada over the past 5 years. The Alberta Improvements for MSK Disorders (AIMS) initiative sought to better understand the COXIB prescribing situation by funding several studies. The objective of this qualitative study was to determine the factors underlying primary care physicians' medication prescribing behaviour during an office visit for an MSK disorder, with particular emphasis on the prescribing of COXIBs. METHODS: The target respondents were Alberta primary care physicians chosen from a stratified random sample to meet a wide range of characteristics. Individual, semi-structured interviews were used to assess decision pathways in four real cases chosen by the physician. A total of 19 interviews were conducted and analysed using an analytic inductive approach. RESULTS: Factors judged as being important to decision pathways in relation to COXIB prescribing for MSK disease included safety, patient characteristics, affordability to patients, availability of samples, drug company marketing practices, habit formation, time contstraints, previous clinical experience of doctors and/or patient with certain drugs and doctors' perception of absolute versus relative risk. Interpretation. Most physicians preferentially prescribed COXIBs subsequent to a complicated, multifactorial, but essentially patient-centred, decision-making process.

Socio-cultural factors influencing prevention and treatment of tuberculosis in immigrant and Aboriginal communities in Canada.

This multi-method study used a participatory action research approach to examine the complex net of socio-cultural factors that influenced behaviour related to tuberculosis (TB) prevention and treatment in the 10 highest risk cultural groups consisting of immigrant and Aboriginal populations in the province of Alberta, Canada. Trained community research associates collected qualitative interview data and helped with interpretation and evaluation. A community advisory committee established foundation principles and monitored the ethical and cultural appropriateness of the research process. A key finding is that although patients with active disease learn about TB from health professionals, people in high-risk populations need to learn more about TB transmission and prevention prior to contact. This is particularly important given that lack of knowledge of TB was strongly associated with negative attitudes towards TB and a worse experience of the disease. The study results underline the need for accessible and culturally appropriate health education about TB in the high risk groups. This can be accomplished in collaboration with lay people, particularly those who have recovered from active TB, their family members and health workers from the community.

Oxidative stress and heart failure.

Despite advances in treatment, chronic congestive heart failure carries a poor prognosis and remains a leading cause of cardiovascular death. Accumulating evidence suggests that reactive oxygen species (ROS) play an important role in the development and progression of heart failure, regardless of the etiology. Under pathophysiological conditions, ROS have the potential to cause cellular damage and dysfunction. Whether the effects are beneficial or harmful will depend upon site, source and amount of ROS produced, and the overall redox status of the cell. All cardiovascular cell types are capable of producing ROS, and the major enzymatic sources in heart failure are mitochondria, xanthine oxidases and the nonphagocytic NADPH oxidases (Noxs). As well as direct effects on cellular enzymatic and protein function, ROS have been implicated in the development of agonist-induced cardiac hypertrophy, cardiomyocyte apoptosis and remodelling of the failing myocardium. These alterations in phenotype are driven by redox-sensitive gene expression, and in this way ROS may act a potent intracellular second messengers. Recent experimental studies have suggested a possible causal role for increased ROS in the development of contractile dysfunction following myocardial infarction and pressure overload, however the precise contribution of different cellular and enzymatic sources involved remain under investigation.

Assessing mental capacity in Canadian Aboriginal seniors.

In recent years, researchers and practitioners have begun to modify existing cognitive assessment instruments and develop new tools in order to increase the accuracy of mental capacity evaluations among seniors in cross-cultural settings. Based on a review of the literature and consultations with members of the Aboriginal capacity assessment committee at the Royal Alexandra Hospital in Edmonton, Canada, during the summer of 1998, the authors argue that both the process by which capacity assessments are conducted and the content of the assessment instruments are problematic. The article summarizes the difficulties that differing degrees of acculturation within and between Aboriginal groups create for cognitive evaluations. It recommends steps that mental health professionals can follow to develop meaningful assessment strategies for Aboriginal seniors that reflect both the content and the interactional processes that characterize their traditional cultural orientations.

Structure of rat parvalbumin with deleted AB domain: implications for the evolution of EF hand calcium-binding proteins and possible physiological relevance.

Among the EF-hand Ca(2+)-binding proteins, parvalbumin (PV) and calbindin D9k (CaB) have the function of Ca(2+) buffers. They evolved from an ancestor protein through two phylogenetic pathways, keeping one pair of EF-hands. They differ by the extra helix-loop-helix (AB domain) found in PV and by the linker between the binding sites. To investigate whether the deletion of AB in PV restores a CaB-like structure, we prepared and solved the structure of the truncated rat PV (PVratDelta37) by X-ray and NMR. PVratDelta37 keeps the PV fold, but is more compact, having a well-structured linker, which differs remarkably from CaB. PvratDelta37 has no stable apo-form, has lower affinity for Ca(2+) than full-length PV, and does not bind Mg(2+), in contrast to CaB. Structural differences of the hydrophobic core are partially responsible for lowering the calcium-binding affinity of the truncated protein. It can be concluded that the AB domain, like the linker of CaB, plays a role in structural stabilization. The AB domain of PV protects the hydrophobic core, and is required to maintain high affinity for divalent cation binding. Therefore, the AB domain possibly modulates PV buffer function.

Divergent biological actions of coronary endothelial nitric oxide during progression of cardiac hypertrophy.

Coronary endothelial NO synthase expression and NO bioactivity were investigated at sequential stages during the progression of left ventricular hypertrophy. Male guinea pigs underwent abdominal aortic banding or sham operation. Left ventricular contractile function was quantified in isolated ejecting hearts. Coronary endothelial and vasodilator function were assessed in isolated isovolumic hearts in response to boluses of bradykinin (0.001 to 10 micromol/L), substance P (0.01 to 100 micromol/L), diethylamine NONOate (DEA-NO) (0.1 to 1000 micromol/L), N(G)-monomethyl-L-arginine monoacetate (L-NMMA) (10 mmol/L), and adenosine (10 mmol/L). At a stage of compensated left ventricular hypertrophy (3 weeks), left ventricular endothelial NO synthase protein expression was unaltered (Western blot and immunocytochemistry). Vasoconstriction in response to L-NMMA was increased in banded animals compared with sham-operated animals (13.8+/-2.1% versus 6.2+/-1.3%, n=10; P<0.05), but agonist- and DEA-NO-induced vasodilation was similar in the 2 groups. At a stage of decompensated left ventricular hypertrophy (8 to 10 weeks), left ventricular endothelial NO synthase protein expression was significantly lower in banded animals (on Western analysis: banded animals, 7.8+/-0.4 densitometric units; sham-operated animals, 12.2+/-1.7 densitometric units; n=5; P<0.05). At this time point, vasoconstriction in response to L-NMMA was similar in the 2 groups, but vasodilatation in response to bradykinin (30.9+/-2.4% versus 39.7+/-2.2%, n=10; P<0.05), DEA-NO (26.2+/-1.8% versus 34.6+/-1.8%, n=10; P<0.05), and adenosine (24.3+/-2.0% versus 35.7+/-2.0%, n=10; P<0.01) was attenuated in banded animals. These findings indicate that there is an increase in the basal activity of NO (without a significant change in endothelial NO synthase expression) in early compensated left ventricular hypertrophy, followed by a decrease in both endothelial NO synthase expression and NO bioactivity during the transition to myocardial failure.

Pharmaceutical care research and education project: pharmacists' interventions.

OBJECTIVES: To describe the processes of care used by community pharmacists participating in the Pharmaceutical Care Research and Education Project (PREP) in terms of drug-related problems (DRPs), pharmacists' recommendations, and status of DRPs at follow-up, and to determine characteristics associated with DRPs. DESIGN: Descriptive analysis of the treatment group from a larger randomized, controlled cluster design. SETTING: Five independent community pharmacies in Alberta. PARTICIPANTS: One hundred fifty-nine patients who were covered under Alberta Health and Wellness's senior drug benefit plan (i.e., 65 years or older), were taking three or more medications concurrently according to pharmacy records, were able to complete telephone interviews as determined by pharmacists, maintained residence in Alberta for 12 of the 15 study months, agreed to receive their prescription medications only from the study pharmacy during the study period, and provided informed consent. MAIN OUTCOME MEASURES: Frequency of DRPs, recommendations, status of DRPs, and analysis of clinical results as determined during pharmacists' follow-up care. RESULTS: In telephone surveys, patients reported taking 4.7 prescription medications per day, but pharmacists documented 8.7 prescription medications per day in their records. Pharmacists documented 559 DRPs, a mean (+/- SD) of 3.9+/-3.2 problems per patient. Approximately 39% of problems were actual DRPs, while 60% were potential DRPs. Medical conditions associated most frequently with a DRP involved the respiratory, cardiovascular, and musculoskeletal systems. The most common DRP categories were "patient requires drug therapy" or "patient requires influenza or pneumococcal vaccination." Pharmacists wrote 551 initial clinical notes using the subjective, objective, assessment, plan (SOAP) format, and they recorded 346 follow-up interventions, also using SOAP notes. Counseling, preventive consultations, and clinical monitoring represented 40% of their recommendations. In 80% of situations, the pharmacist made the recommendation directly to the patient. On follow-up, 40% of the 559 DRPs identified were resolved, controlled, or improved. Patients accepted 76% of pharmacists' recommendations, and physicians accepted 72% of pharmacists' suggested resolutions of DRPs. Pharmacists were more likely to follow up about actual DRPs, as compared with potential ones; overall, they followed up on 62% of identified DRPs. CONCLUSION: Pharmacists identified more DRPs for study patients than previous community-based, observational studies have reported. Undertreatment appears to be a prevalent DRP. Community pharmacists' recommendations to prevent and resolve DRPs were made primarily to patients and were well accepted. More follow-up was needed for all DRPs. When follow-up occurred, the DRP results generally showed improvement.

Pharmaceutical care research and education project: patient outcomes.

OBJECTIVE: To compare patients' adherence to therapy, expectations, satisfaction with pharmacy services, and health-related quality of life (HRQOL) after the provision of pharmaceutical care with those of patients who received traditional pharmacy care. DESIGN: Randomized controlled cluster design. SETTING: Sixteen community pharmacies in Alberta, Canada. PATIENTS AND OTHER PARTICIPANTS: Ambulatory elderly (> or = 65 years of age) patients covered under Alberta Health & Wellness's senior drug benefit plan and who were concurrently using three or more medications according to pharmacy profiles. INTERVENTION: Pharmacies were randomly assigned to either treatment (intervention) or control (traditional pharmacy care) groups. Patients at treatment pharmacies were recruited into the study, and pharmacists provided comprehensive pharmaceutical care services. Pharmacists at control pharmacies continued to provide traditional pharmacy care. MAIN OUTCOME MEASURES: Study participants' opinions, adherence to therapy, and scores on the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS: Compared with those of patients receiving traditional care, treatment patients' expectations that their pharmacist would perform activities congruent with pharmaceutical care changed over the study period. Treatment patients' satisfaction with the constructs "trust," "evaluation and goal setting," and "communicates with doctor" were also positively affected. HRQOL and patient adherence were not significantly affected by pharmaceutical care interventions. CONCLUSION: Successful implementation of a pharmaceutical care practice model has the potential to increase patients' satisfaction with their pharmacists' activities and may increase patients' expectations that pharmacists will work on their behalf to assist them with their health care needs. If pharmaceutical care affects patients' HRQOL, instruments more specific than the SF-36 may be needed to detect the differences.

Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.

To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.

Use of focus groups to assess the educational needs of the primary care physician for the management of asthma.

OBJECTIVES: To determine the educational needs of primary care physicians, in the management of patients with asthma. DESIGN: Focus group discussions with physicians, pharmacists, respiratory therapists and patients. SETTING: Metropolitan Edmonton, Alberta, Canada. PARTICIPANTS: Out of an original mail request to 100 potential recruits, 52 people attended the focus group sessions. These included physicians, pharmacists, respiratory therapists, adult patients and paediatric patients accompanied by their parents. MAIN OUTCOME MEASURE: Consensus of the specific group being interviewed using facilitator-mediated responses, to identify problems in the care of asthma patients and appropriate educational methods to improve the situation. RESULTS: Both diagnostic and treatment concerns were identified by the primary care physicians and others in the study. Confusion with infection was the most common diagnostic problem. Major treatment problems involved confusion about aspects of management strategy and a lack of communication between physicians, patients and other members of the health care team. Poor patient compliance and patients changing doctors frequently were also of major concern. There were inconsistencies in the treatment of asthma between physicians. While most physicians felt that they were up-to-date in management, Asthma Control Guidelines were seldom followed. CONCLUSIONS: There is an urgent need for continuing medical education, not only in management but also in communication with patients and with other members of the health care team. The data permit the development of an ongoing educational programme which is practical and designed to deal with the issues identified in this survey.

ATP synthesis during low-flow ischemia: influence of increased glycolytic substrate.

BACKGROUND: Our goals were to (1) simulate the degree of low-flow ischemia and mixed anaerobic and aerobic metabolism of an acutely infarcting region; (2) define changes in anaerobic glycolysis, oxidative phosphorylation, and the creatine kinase (CK) reaction velocity; and (3) determine whether and how increased glycolytic substrate alters the energetic profile, function, and recovery of the ischemic myocardium in the isolated blood-perfused rat heart. METHODS AND RESULTS: Hearts had 60 minutes of low-flow ischemia (10% of baseline coronary flow) and 30 minutes of reperfusion with either control or high glucose and insulin (G+I) as substrate. In controls, during ischemia, rate-pressure product and oxygen consumption decreased by 84%. CK velocity decreased by 64%; ATP and phosphocreatine (PCr) concentrations decreased by 51% and 63%, respectively; inorganic phosphate (P(i)) concentration increased by 300%; and free [ADP] did not increase. During ischemia, relative to controls, the G+I group had similar CK velocity, oxygen consumption, and tissue acidosis but increased glycolysis, higher [ATP] and [PCr], and lower [P(i)] and therefore had a greater free energy yield from ATP hydrolysis. Ischemic systolic and diastolic function and postischemic recovery were better. CONCLUSIONS: During low-flow ischemia simulating an acute myocardial infarction region, oxidative phosphorylation accounted for 90% of ATP synthesis. The CK velocity fell by 66%, and CK did not completely use available PCr to slow ATP depletion. G+I, by increasing glycolysis, slowed ATP depletion, maintained lower [P(i)], and maintained a higher free energy from ATP hydrolysis. This improved energetic profile resulted in better systolic and diastolic function during ischemia and reperfusion. These results support the clinical use of G+I in acute MI.