Indigenous perspectives on wellness and health in Canada: study protocol for a scoping review.

BACKGROUND: Indigenous communities are often portrayed from a deficit-based lens; however, Indigenous communities have self-determined perspectives of health and well-being that are strength based. The objective of this study will be to systematically map the literature on perspectives, concepts, and constructs of wellness and well-being in Indigenous communities in Canada. METHODS: A scoping review protocol was designed following the Arksey and O'Malley framework. We will search the following electronic databases (from inception onwards): MEDLINE, EMBASE, Web of Science, CINAHL, Academic Search Complete, Anthropology Plus, Bibliography of Native North Americans, Canadian Business and Current Affairs, and Circumpolar Health Bibliographic Database. Grey literature will be identified through searching dissertation databases, Google Scholar, and conference abstracts. We will include all types of literature in English, published and unpublished, including any study design, reviews and meta-analyses, dissertations, reports, and books. The literature considered should describe or reflect Indigenous perspectives that identify concepts or constructs related to well-being or wellness; literature can be from any setting in Canada. Two reviewers will independently screen all citations, full-text reports, and abstract data. Data analysis will involve quantitative descriptions (e.g. frequencies) and qualitative content analysis methods. DISCUSSION: This review will provide a synthesis of the literature on Indigenous perspectives, concepts, and constructs of wellness and well-being in Canada. We anticipate the study will contribute to improve our understanding of how Indigenous communities conceptualize and embody wellness. Our findings will provide a basis for engaging Indigenous stakeholders in future health research and informing future interpretations of how wellness is conceptualized, whether written or unwritten.

Long-term recall of social relationships related to addiction and HIV risk behaviors.

BACKGROUND: Social relationships have been demonstrated as a key predictor of relapse among addicted persons and are likely to be important determinants of HIV risk behaviors also. However, the degree to which this population can reliably and consistently identify important people (IPs) in retrospect has been understudied. METHODS: Using the modified Important People and Activities questionnaire, we investigated to what degree IPs were dropped, added, or retained, and whether data about individual IPs were reported accurately on 6- and 12-month follow up periods using a sample of 50 drug or alcohol abusing participants. RESULTS: We found that IPs were largely retained, and that those retained versus dropped/added differed by their reaction to participant alcohol/drug use, as well as frequency of contact. We further found that there were differences in reliability of data describing specific IPs. While both 6- and 12-month follow up periods led to reliabilities ranging from excellent to fair, we found poorer reliability on responses to recall of "frequency of contact" and "reactions to drinking", as well as "reactions to drug use". CONCLUSION: Future investigations of reliability of social relationships recalled retrospectively should attempt to examine possible systematic biases in addition to the reliability of specific IP data. More sophisticated studies are needed on factors associated with systematic variation in reporting of aspects of social relationships that are associated with addictions or HIV risk outcomes.

Examining the reliability of alcohol/drug use and HIV-risk behaviors using Timeline Follow-Back in a pilot sample.

Research on the course of substance use disorders (SUDs) faces challenges in assessing behavior over lengthy time periods. Calendar-based methods, like the Timeline Followback (TLFB), may overcome these challenges. This study assessed the reliability of self-reported weekly alcohol use, drug use, and HIV-risk behaviors over the past 90 days using an interview TLFB. Individuals with SUD in outpatient treatment (N = 26) completed the TLFB at baseline and then a week later with separate interviewers. Weekly ratings were aggregated across 4 week intervals for each administration. Intra-class correlations were used to compare agreement between the two administrations. Reliabilities for alcohol and drug use ratings ranged from good to excellent for most drug categories (ICCs = 0.76 - 1.00), except opioid use (other than heroin) and sedative use produced sub-standard reliabilities (ICCs = 0.29 - 0.74). HIV-risk behavior reliabilities also ranged from good to excellent (ICCs = 0.70 - 0.97), but were substandard for the number of casual sex partners for some intervals (ICCs = 0.29, 0.63). Findings extend support for the use of TLFB to produce reliable assessments of many drugs and HIV-risk behaviors across longitudinal intervals.

The influence of comorbid disorders on the episodicity of bipolar disorder in youth.

OBJECTIVE: Bipolar disorder (BP) frequently co-occurs with other psychiatric disorders. We examine whether course of anxiety disorders (ANX), attention deficit hyperactivity disorder (ADHD), disruptive behavior disorders (DBD), and substance use disorders (SUD) influence likelihood of recovery and recurrence of depression and mania in BP youth. METHOD: Weekly ratings of psychiatric disorder intensity were obtained from 413 participants of the Course and Outcome of BP Youth project, followed for an average of 7.75 years. Multiple-event Cox proportional hazards regression analyses examined worsening of comorbid disorders as predictors of mood episode recovery and recurrence. RESULTS: Increased severity in ANX and SUD predicted longer time to recovery and less time to next depressive episode, and less time to next manic episode. Multivariate models with ANX and SUD found that significant effects of ANX remained, but SUD only predicted longer time to depression recovery. Increased severity of ADHD and DBD predicted shorter time to recurrence for depressive and manic episodes. CONCLUSION: There are significant time-varying relationships between the course of comorbid disorders and episodicity of depression and mania in BP youth. Worsening of comorbid conditions may present as a precursor to mood episode recurrence or warn of mood episode protraction.

Oral treatment of rodents with fipronil for feed-through and systemic control of sand flies (Diptera: Psychodidae).

The sand fly Phlebotomus papatasi Scopoli is the vector of Leishmania major (Yakimoff & Schokhor), which is maintained in populations of burrowing rodents. The purpose of this study was to conduct a laboratory study to determine the efficacy of oral treatment of rodents with fipronil for control of sand flies that feed on rodent feces as larvae or on rodent blood as adults. We determined through larval bioassays that fipronil was eliminated in feces of orally-treated hamsters at a level that was significantly toxic to sand fly larvae for 21 d after the hamsters had been withdrawn from a fipronil-treated diet. Through bloodfeeding bioassays, we also found that fipronil was present in the peripheral blood of hamsters at a concentration that was significantly toxic to bloodfeeding adult female sand flies for 49 d after the hamsters had been withdrawn from their treated diet. The results of this study suggest that fipronil acts as well as or better than feed-through or systemic insecticides that previously have been measured against sand flies, and is particularly promising because this single compound acts against both larvae and bloodfeeding adults. An area-wide approach using rodent baits containing a fipronil could suppress vector populations that originate in the vicinity of rodent reservoirs, and could be used to eliminate the most epidemiologically important part of the vector population: female sand flies that take bloodmeals on rodent reservoirs.

A 4-year prospective observational follow-up study of course and predictors of course in body dysmorphic disorder.

BACKGROUND: This report prospectively examines the 4-year course, and predictors of course, of body dysmorphic disorder (BDD), a common and often severe disorder. No prior studies have prospectively examined the course of BDD in individuals ascertained for BDD. Method The Longitudinal Interval Follow-Up Evaluation (LIFE) assessed weekly BDD symptoms and treatment received over 4 years for 166 broadly ascertained adults and adolescents with current BDD at intake. Kaplan-Meier life tables were constructed for time to remission and relapse. Full remission was defined as minimal or no BDD symptoms, and partial remission as less than full DSM-IV criteria, for at least 8 consecutive weeks. Full relapse and partial relapse were defined as meeting full BDD criteria for at least 2 consecutive weeks after attaining full or partial remission respectively. Cox proportional hazards regression examined predictors of remission and relapse. RESULTS: Over 4 years, the cumulative probability was 0.20 for full remission and 0.55 for full or partial remission from BDD. A lower likelihood of full or partial remission was predicted by more severe BDD symptoms at intake, longer lifetime duration of BDD, and being an adult. Among partially or fully remitted subjects, the cumulative probability was 0.42 for subsequent full relapse and 0.63 for subsequent full or partial relapse. More severe BDD at intake and earlier age at BDD onset predicted full or partial relapse. Eighty-eight percent of subjects received mental health treatment during the follow-up period. CONCLUSIONS: In this observational study, BDD tended to be chronic. Several intake variables predicted greater chronicity of BDD.

Laboratory evaluation of rubidium as a long-lasting marker for bloodfeeding sand flies (Diptera: Psychodidae).

The objective of this study was to evaluate the use of the trace element rubidium (Rb) as a long-lasting systemic biomarker for bloodfeeding females of the sand fly Phlebotomus papatasi Scopoli. Baits containing Rb chloride were found to be palatable to hamsters in this study. We were able to detect Rb using a portable X-ray fluorescence analyzer in all sand flies that fed on Rb-treated hamsters for at least 14 d postbloodmeal. We also detected Rb in sand flies that took a bloodmeal from hamsters up to 10 d after the hamsters were withdrawn from a Rb-treated diet. Results of this study constitute proof of concept for the incorporation of Rb chloride into rodent baits for marking bloodfeeding sand flies, and suggest that Rb marking could be used as a technique for evaluating rodent-targeted sand fly control methods and in ecological studies on sand flies.

Evaluation of three feed-through insecticides using two rodent and two sand fly species as models.

The efficacy of 3 rodent feed-through insecticides (novaluron, pyriproxyfen, and ivermectin) was determined against larvae of the sand flies Phlebotomus duboscqi and P. papatasi using Syrian hamsters (Mesocricetus auratus) and Mongolian gerbils (Meriones unguiculatus) as laboratory models. For each insecticide, there were no significant differences between the longevity or percentage survival of sand fly larvae that had been fed feces of treated rodents for each sand fly or rodent species pairing. The results of this study suggest that larvae of P. duboscqi and P. papatasi are equally susceptible to the concentrations of the rodent feed-through insecticides tested in this study and that these insecticides are pharmacologically compatible with different rodent/sand fly interactions.

Oral treatment of rodents with insecticides for control of sand flies (Diptera: Psychodidae) and the fluorescent tracer technique (FTT) as a tool to evaluate potential sand fly control methods.

In laboratory studies, insecticides (diflubenzuron, novaluron, methoprene and, pyriproxyfen) that have been incorporated into rodent diets were effective as feed-throughs against sand fly larvae. Novaluron also was effective against sand fly larvae at low concentrations and under simulated field conditions. Ivermectin has been shown to be effective as a systemic insecticide, killing 100% of blood-feeding sand flies for up to seven d after rodents were treated. The fluorescent tracer technique (FTT) is the use of certain fluorescent dyes (rhodamine B or uranine O) as feed-through transtadial biomarkers for phlebotomine sand flies, systemic biomarkers for blood-feeding sand flies, and permanent markers for nectar-feeding sand flies. The results of these laboratory studies provide proof of concept for the FTT and indicate that the FTT could be used to delineate specific foci with rodent/sand fly associations that would be susceptible to control by using feed-through or systemic insecticides, or foci where insecticide-treated sugar baits could be used against sand flies.

Personality traits as prospective predictors of suicide attempts.

OBJECTIVE: To examine higher order personality factors of negative affectivity (NA) and disinhibition (DIS), as well as lower order facets of impulsivity, as prospective predictors of suicide attempts in a predominantly personality disordered sample. METHOD: Data were analyzed from 701 participants of the Collaborative Longitudinal Personality Disorders Study with available follow-up data for up to 7 years. Cox proportional hazards regression analyses was used to examine NA and DIS, and facets of impulsivity (e.g. urgency, lack of perseverance, lack of premeditation and sensation seeking), as prospective predictors of suicide attempts. RESULTS: NA, DIS and all facets of impulsivity except for sensation seeking were significant in univariate analyses. In multivariate models which included sex, childhood sexual abuse, course of major depressive disorder and substance use disorders, only NA and lack of premeditation remained significant in predicting suicide attempts. DIS and the remaining impulsivity facets were not significant. CONCLUSION: NA emerged as a stronger and more robust predictor of suicide attempts than DIS and impulsivity, and warrants greater attention in suicide risk assessment. Distinguishing between facets of impulsivity is important for clinical risk assessment.

Juvenile-onset OCD: clinical features in children, adolescents and adults.

OBJECTIVE: To examine clinical correlates of juvenile-onset OCD across the lifespan. METHOD: Data collected at the intake interview from 257 consecutive participants with juvenile-onset OCD (20 children, 44 adolescents and 193 adults) in a naturalistic study of the clinical course of OCD were examined. Participants and parents of juvenile participants completed a structured diagnostic interview, rater-administered severity measures and self-report questionnaires. RESULTS: Children and adolescents (i.e. juveniles) shared similar features with the exception of age at onset and OCD symptom expression. Clinically meaningful differences between juvenile and adult participants were also found. Compared with adults, juveniles were more likely to be male, recall an earlier age at OCD onset and have different lifetime comorbidity patterns. CONCLUSION: Juvenile-onset OCD symptom expression is remarkably similar across the lifespan. However, findings also suggest clinically meaningful differences between juveniles and adults. Future work using a prospective design will improve our understanding of course patterns of juvenile-onset OCD.

Heterologous prime-boost strategy to immunize very young infants against measles: pre-clinical studies in rhesus macaques.

Infants in developing countries are at high risk of developing severe clinical measles if they become infected during the "window of vulnerability" (age 4-9 months), when declining maternal antibodies do not protect against wild virus, yet impede successful immunization by attenuated measles vaccine. We developed two Sindbis replicon-based DNA vaccines expressing measles virus hemagglutinin and fusion protein with the goal of priming young infants to respond safely and effectively to subsequent boosting with attenuated measles vaccine. Intradermal prime with DNA vaccines by needle-free injection followed by aerosol or parenteral boost with licensed measles vaccine was well tolerated by juvenile and young infant rhesus macaques, and protected against clinical measles and viremia on wild-type virus challenge. A proteosome-measles vaccine administered alone (three doses) or as a boost following DNA vaccine priming was also safe and protective. These promising results pave the way for clinical trials to assess this prime-boost strategy.

Pre-clinical evaluation of a CEA DNA prime/protein boost vaccination strategy against colorectal cancer.

In preparation for a clinical trial in patients diagnosed with colorectal cancer, a vaccination strategy targeting the carcinoembryonic antigen (CEA) was evaluated in mice using a GMP-produced plasmid DNA vaccine, CEA66, encoding a truncated form of the tumour-associated antigen, CEA. The GMP-produced CEA DNA vaccine was also evaluated for toxicity. Repeated intradermal administration of the GMP-produced vaccine using a novel needle-free jet injection device (Biojector) induced robust CD4 and CD8 T-cell responses in mice, and did not result in any vaccine-related toxicity. In a heterologous DNA prime/protein boost setting, cellular immune responses were of higher magnitude in animals primed with CEA66 DNA than in animals receiving repeated doses of recombinant CEA protein. These responses were further enhanced if recombinant murine granulocyte-macrophage colony-stimulating factor was given as an adjuvant prior to vaccination. In contrast to repeated administration of recombinant CEA protein as a single modality vaccine, the heterologous CEA66 DNA prime/rCEA boost vaccination strategy resulted in a qualitatively broader immune response, and supports clinical testing of this vaccination regimen in humans.

Delusional versus nondelusional body dysmorphic disorder: clinical features and course of illness.

DSM-IV's classification of body dysmorphic disorder (BDD) is controversial. Whereas BDD is classified as a somatoform disorder, its delusional variant is classified as a psychotic disorder. However, the relationship between these BDD variants has received little investigation. In this study, we compared BDD's delusional and nondelusional variants in 191 subjects using reliable and valid measures that assessed a variety of domains. Subjects with delusional BDD were similar to those with nondelusional BDD in terms of most variables, including most demographic features, BDD characteristics, most measures of functional impairment and quality of life, comorbidity, and family history. Delusional and nondelusional subjects also had a similar probability of remitting from BDD over 1 year of prospective follow-up. However, delusional subjects had significantly lower educational attainment, were more likely to have attempted suicide, had poorer social functioning on several measures, were more likely to have drug abuse or dependence, were less likely to currently be receiving mental health treatment, and had more severe BDD symptoms. However, when controlling for BDD symptom severity, the two groups differed only in terms of educational attainment. These findings indicate that BDD's delusional and nondelusional forms have many more similarities than differences, although on several measures delusional subjects evidenced greater morbidity, which appeared accounted for by their more severe BDD symptoms. Thus, these findings offer some support for the hypothesis that these two BDD variants may constitute the same disorder. Additional studies are needed to examine this issue, which may have relevance for other disorders with both delusional and nondelusional variants in DSM.

The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements.

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.

Comparison of systemic exposure to nemifitide following two methods of subcutaneous administration to healthy volunteers.

The purpose of this study was to evaluate the safety and pharmacokinetics of nemifitide, a synthetic antidepressant pentapeptide, following its subcutaneous (s.c.) administration by standard needle injection or by a needle-free (Biojecttrade mark) injection and to compare these two routes of administration for systemic exposure. This small-scale, randomized, single-dose, parallel design, open-label pilot study consisted of three treatment groups of four subjects each dosed as follows: group 1: 40 mg of nemifitide administered by standard needle/syringe and groups 2 and 3: 40 and 80 mg nemifitide, respectively, administered by using a needle-free (Bioject injection delivery system. Plasma concentrations of nemifitide were determined by LC/MS/MS in blood samples collected at 10 min and 0.5, 1, 2, 4, 6 and 24 h after dosing. PK parameters, including observed C(max), T(max) and AUC(0-24), were calculated and statistical analysis of the data was conducted. Safety assessments (dosing site evaluations) were done at 0.5, 1, 5 and 24 h after dosing. Vital signs and clinical laboratory tests were taken on day 1 prior to dosing and at 24 h post-dose. Adverse experiences in all subjects were observed only as drug-related local reactions at the injection sites. All were considered mild in severity and transient (resolved by 24 h after dosing). T(max) was observed at 10 min after dose and was the same in all subjects. In the three dosing groups, 1 (40 mg), 2 (40 mg) and 3 (80 mg), observed C(max) values were 226, 245 and 440 ng/ml, respectively, and AUC(0-24) values were 108, 106 and 205 ng.h/ml, respectively. Ratios of AUC(0-24) and observed C(max) for nemifitide in plasma between groups 1 and 2 were within the 80%-125% range, indicating that the two modes of drug administration resulted in similar systemic exposure to nemifitide. Pharmacokinetic parameters (AUC(0-24) and C(max)) indicate dose-proportionality between the doses of 40 and 80 mg.

Randomized phase II study of two gemcitabine schedules for patients with impaired performance status (Karnofsky performance status

PURPOSE: This randomized phase II study compared two treatment schedules of gemcitabine in patients with non-small-cell lung cancer (NSCLC) and impaired Karnofsky performance status (KP). Primary objectives were to record changes from baseline KP and to assess symptom palliation. Secondary objectives were overall survival, tumor response, and toxicity. PATIENTS AND METHODS: Patients with stage IIIb and IV NSCLC and KP

Stressful life events as predictors of functioning: findings from the collaborative longitudinal personality disorders study.

OBJECTIVE: Although much attention has been given to the effects of adverse childhood experiences on the development of personality disorders (PDs), we know far less about how recent life events influence the ongoing course of functioning. We examined the extent to which PD subjects differ in rates of life events and the extent to which life events impact psychosocial functioning. METHOD: A total of 633 subjects were drawn from the Collaborative Longitudinal Personality Disorders Study (CLPS), a multi-site study of four personality disorders--schizotypal (STPD), borderline (BPD), avoidant (AVPD), obsessive-compulsive (OCPD)--and a comparison group of major depressive disorders (MDD) without PD. RESULTS: Borderline personality disorder subjects reported significantly more total negative life events than other PDs or subjects with MDD. Negative events, especially interpersonal events, predicted decreased psychosocial functioning over time. CONCLUSION: Our findings indicate higher rates of negative events in subjects with more severe PDs and suggest that negative life events adversely impact multiple areas of psychosocial functioning.

Longitudinal diagnostic efficiency of DSM-IV criteria for obsessive-compulsive personality disorder: a 2-year prospective study.

OBJECTIVE: To examine the longitudinal diagnostic efficiency of the DSM-IV criteria for obsessive-compulsive personality disorder (OCPD). METHOD: At baseline, criteria and diagnoses were determined using diagnostic interviews, and blinded assessments were performed 24 months later with 550 participants. Diagnostic efficiency indices (conditional probabilities, total predictive power, and kappa) were calculated for each criterion determined at baseline, using the independent OCPD diagnosis at follow-up as the standard. RESULTS: Longitudinal diagnostic efficiencies for the OCPD criteria varied; findings suggested the overall predictive utility of 'preoccupied with details', 'rigid and stubborn', and 'reluctant to delegate'. CONCLUSION: These findings suggest the predictive validity of three cognitive-interpersonal OCPD criteria.