Development of Best Practice Guidelines for Primary Care to Support Patients Who Use Substances.

INTRODUCTION: People who use substances often mistrust the primary care system, impeding access. OBJECTIVES: To build on research clarifying how to improve patients' feelings of safety, through co-creating best practice guidelines with physicians and patient representatives. METHODS: After obtaining Research Ethics Board approval, this qualitative study engaged 22 participants including patients, physicians, and health system partners. We held a series of workshops, co-facilitated by patients and researchers, corresponding to 3 phases of the research: (1) establishment of cultural safety processes for participants during the workshops; (2) a facilitated, collaborative world café to develop guideline content; (3) validation of best practice guidelines. An implementation plan was developed and implemented. Finally, an external peer review was conducted by McGill University. RESULTS: Best practices guidelines were developed giving the patient perspective on how to enhance primary care, as follows: (1) become trauma informed; (2) consider your clinical environment; (3) build a network; (4) supply an array of resources; (5) co-create a long-term treatment plan; (6) help me to stay healthy; (7) ensure timely access to specialized medical and surgical care; (8) be an advocate; (9) ask for feedback; (10) follow up. Resources were developed and disseminated. CONCLUSION: The best practice guidelines reflect the patients' perspectives on common challenges patients have encountered, which impede their access to primary care. They support primary care physicians in providing more effective services to this challenging population of patients.

Workloads of forward and backline adolescent rugby players: a pilot study.

Background: There is minimal research on workloads of adolescent rugby players. Therefore, the main aim of this study was to determine the workloads placed on a cohort of South African adolescent rugby players (n = 17), during an in-season period. Methods: Session RPE ratings were collected daily, 30 minutes after the training session concluded, during an 11-week in-season period. The training load was calculated as the session ratings of perceived exertion multiplied by the session's duration (min). Results: The main finding of the study was that the adolescents in this investigation had similar workloads to elite players but higher workloads than other studies on adolescent rugby players. The forwards (3311±939 arbitrary units; AU) had a higher workload than backline players (2851±1080 AU). There was no difference between forwards and backline players with regards to the acute:chronic workload ratio. Conclusion: Workloads are high in these adolescent players, particularly in the forwards, and are similar to the workloads of elite level rugby players.

Failure to perform assisted deliveries is resulting in an increased neonatal and maternal morbidity and mortality: An expert opinion.

The need to perform assisted vaginal delivery (AVD) has been regarded as self-evident. In high-income countries, rates of AVD range between 5% and 20% of all births. In South Africa, the rate of AVD is only 1%. This has resulted in increased neonatal morbidity and mortality due to intrapartum asphyxia, and increased maternal morbidity and mortality due to a rise in second-stage caesarean deliveries. In this article, we address the possible causes leading to a decrease in AVD and propose measures to be taken to increase the rates of AVD and subsequently reduce morbidity and mortality.

Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer.

Patients with advanced breast cancer often fail to respond to treatment, creating a need to develop novel biomarkers and effective therapeutics. Dopamine (DA) is a catecholamine that binds to five G protein-coupled receptors. We discovered expression of DA type-1 receptors (D1Rs) in breast cancer, thereby identifying these receptors as novel therapeutic targets in this disease. Strong to moderate immunoreactive D1R expression was found in 30% of 751 primary breast carcinomas, and was associated with larger tumors, higher tumor grades, node metastasis and shorter patient survival. DA and D1R agonists, signaling through the cGMP/protein kinase G (PKG) pathway, suppressed cell viability, inhibited invasion and induced apoptosis in multiple breast cancer cell lines. Fenoldopam, a peripheral D1R agonist that does not penetrate the brain, dramatically suppressed tumor growth in two mouse models with D1R-expressing xenografts by increasing both necrosis and apoptosis. D1R-expressing primary tumors and metastases in mice were detected by fluorescence imaging. In conclusion, D1R overexpression is associated with advanced breast cancer and poor prognosis. Activation of the D1R/cGMP/PKG pathway induces apoptosis in vitro and causes tumor shrinkage in vivo. Fenoldopam, which is FDA (Food and Drug Administration) approved to treat renal hypertension, could be repurposed as a novel therapeutic agent for patients with D1R-expressing tumors.

Relationship between mosquito (Diptera: Culicidae) landing rates on a human subject and numbers captured using CO2-baited light traps.

Capture rates of insectary-reared female Aedes albopictus (Skuse), Anopheles quadrimaculatus Say, Culex nigripalpus Theobald, Culex quinquefasciatus Say and Aedes triseriatus (Say) in CDC-type light traps (LT) supplemented with CO2 and using the human landing (HL) collection method were observed in matched-pair experiments in outdoor screened enclosures. Mosquito responses were compared on a catch-per-unit-effort basis using regression analysis with LT and HL as the dependent and independent variables, respectively. The average number of mosquitoes captured in 1 min by LT over a 24-h period was significantly related to the average number captured in 1 min by HL only for Cx. nigripalpus and Cx. quinquefasciatus. Patterns of diel activity indicated by a comparison of the mean response to LT and HL at eight different times in a 24-h period were not superposable for any species. The capture rate efficiency of LT when compared with HL was ≤15% for all mosquitoes except Cx. quinquefasciatus (43%). Statistical models of the relationship between mosquito responses to each collection method indicate that, except for Ae. albopictus, LT and HL capture rates are significantly related only during certain times of the diel period. Estimates of mosquito activity based on observations made between sunset and sunrise were most precise in this regard for An. quadrimaculatus and Cx. nigripalpus, as were those between sunrise and sunset for Cx. quinquefasciatus and Ae. triseriatus.

Host-specificity of myxoma virus: Pathogenesis of South American and North American strains of myxoma virus in two North American lagomorph species.

The pathogenesis of South American and North American myxoma viruses was examined in two species of North American lagomorphs, Sylvilagus nuttallii (mountain cottontail) and Sylvilagus audubonii (desert cottontail) both of which have been shown to have the potential to transmit the South American type of myxoma virus. Following infection with the South American strain (Lausanne, Lu), S. nuttallii developed both a local lesion and secondary lesions on the skin. They did not develop the classical myxomatosis seen in European rabbits (Oryctolagus cuniculus). The infection at the inoculation site did not resolve during the 20-day time course of the trial and contained transmissible virus titres at all times. In contrast, S. audubonii infected with Lu had very few signs of disseminated infection and partially controlled virus replication at the inoculation site. The prototype Californian strain of myxoma virus (MSW) was able to replicate at the inoculation site of both species but did not induce clinical signs of a disseminated infection. In S. audubonii, there was a rapid response to MSW characterised by a massive T lymphocyte infiltration of the inoculation site by day 5. MSW did not reach transmissible titres at the inoculation site in either species. This might explain why the Californian myxoma virus has not expanded its host-range in North America.

Autologous bone marrow transplantation for children with AML in first remission.

In Children's cancer group (CCG) 2891, newly diagnosed patients with AML were randomized between standard and intensive timing induction therapies. Patients in first remission who lacked an HLA matched family donor were randomized between an autologous bone marrow transplantation (ABMT) where marrow was purged with 4 hydroperoxycyclophosphamide and consolidation chemotherapy. One hundred and thirty seven patients received an ABMT. Myeloid and platelet engraftment occurred at a median of 44 and 42 days, respectively. Disease-free survival (DFS), relapse-free survival and overall survival at 8 years post induction were 47% (95% confidence interval (CI): 38-55), 50% (CI: 42-59) and 55% (CI: 46-63), respectively. Multivariate analysis of DFS showed WBC <50 000/microl and having received intensively timed induction therapy were associated with improved DFS. Recipients who received intensive timed induction therapy and whose WBC was less than 50 000/microl had a DFS at 8 years of 62% (CI: 49-73). Conversely, recipients who received intensive timed induction therapy patients whose WBC was > or =50 000/microl had a DFS of 33% (CI: 17-50), P=0.003. The results confirm previous studies that ABMT is effective post remission therapy for pediatric patients with AML in first remission.

Updates on local anaesthetics.

This article draws from a book entitled: "A practical approach to hazards of local anaesthetic injections" by DP Barnard.

Laboratory evaluation of 21 insect repellents as larvicides and as oviposition deterrents of Aedes albopictus (Diptera: Culicidae).

Twenty-one commercial insect repellent products, including 12 botanical, 6 DEET-based, and 3 synthetic organics, were evaluated as larvicides and as oviposition deterrents of Aedes albopictus. Ten of the 12 botanical products at 0.1% concentration provided 57-100% mortality of laboratory-reared 4th-stage Ae. albopictus larvae at 24 h after treatment. Five of the 6 DEET-based products and 3 synthetic organic repellents at 0.1% concentration induced 88-100% larval mortality at 24 h after treatment. All 12 botanical products proved highly effective oviposition deterrents of Ae. albopictus, resulting in 76-100% effective repellency at 24 h after exposure. The 6 DEET-based repellents and the 3 synthetic organic repellents caused 84-100% effective oviposition repellency of Ae. albopictus at 24 h after exposure. Several botanical repellents previously shown to have minimal protection from mosquito bites proved effective oviposition deterrents. Some commercial topical repellents have good potential for development and use in management of container-inhabiting mosquitoes because they deter oviposition and kill larvae.

Laboratory evaluation of a dyed food marking technique for Culex quinquefasciatus (Diptera: Culicidae).

A method of marking adult Culex quinquefasciatus by feeding the larvae commercial hog chow dyed with methylene blue, Giemsa, and crystal violet was evaluated under laboratory conditions. Of 243 mosquitoes fed the dyed food, 230 had visible marks (94.6%). The dyed food increased the egg-adult development time from 11.4 to 12.1 d. After 9 d, 82.5% of adult mosquitoes dyed as larvae could be identified, and remained detectable for up to 15 d, their maximum laboratory life.

In vitro and in vivo influenza virus-inhibitory effects of viramidine.

Viramidine, the 3-carboxamidine derivative of ribavirin, was effective against a spectrum of influenza A (H1N1, H3N2 and H5N1) and B viruses in vitro, with the 50% effective concentration (EC50) ranging from 2 to 32 microg/ml. The mean 50% cytotoxic concentration (CC50) in the MDCK cells used in these experiments was 760 microg/ml. Ribavirin, run in parallel, had a similar antiviral spectrum, with EC50 values ranging from 0.6 to 5.5 microg/ml; the mean CC50 for ribavirin was 560 microg/ml. Oral gavage administrations of viramidine or ribavirin to mice infected with influenza A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), B/Hong Kong/5/72 or B/Sichuan/379/99 viruses were highly effective in preventing death, lessening decline in arterial oxygen saturation, inhibition of lung consolidation and reducing lung virus titers. The minimum effective dose of viramidine in these studies ranged from 15 to 31 mg/kg/day, depending upon the virus infection, when administered twice daily for 5 days beginning 4 h pre-virus exposure. The LD50 of the compound was 610 mg/kg/day. Ribavirin's minimum effective dose varied between 18 and 37.5 mg/kg/day with the LD50 determined to be 220 mg/kg/day. Viramidine's efficacy was also seen against an influenza A/NWS/33 (H1N1) virus infection in mice, when the compound was administered in the drinking water, the minimum effective dose being 100 mg/kg/day. Delay of the initiation of either viramidine or ribavirin therapy, using the approximate 1/3 LD50 dose of each, was protective as late as 48 h after exposure to the A/NWS/33 virus. While both compounds appear to have similar efficacy against influenza virus infections, when one considers the lesser toxicity, viramidine may warrant further evaluation as a possible therapy for influenza.

Effects of forced egg-retention in Aedes albopictus on adult survival and reproduction following application of DEET as an oviposition deterrent.

The insect repellent DEET (0.1% concentration), used as a mosquito oviposition deterrent in the laboratory, influenced the retention and maintenance of mature eggs by caged gravid female Aedes albopictus Skuse. This egg-retention mechanism could benefit survival because the gravid females were ultimately able to lay maintained eggs upon availability of water, but the length of forced egg-retention time reduced the number of eggs laid per female. Gravid females with retained eggs also laid a higher percentage of eggs that failed to tan, and this percentage increased with time duration of egg-retention. Percent egg hatch was not significantly affected by DEET when used as an oviposition deterrent; however, percent hatch was affected by time duration of egg-retention in both treated (exposed to DEET) and untreated (control) gravid females. The rate of egg hatch was considerably reduced after three weeks of retention; this reduction declined to zero for treated and control females at six and four weeks post-treatment, respectively. The fecundity and fertility of gravid female Ae. albopictus were affected by the time duration of forced egg-retention.

Treatment-related myelodysplastic syndrome/acute myeloid leukemia in survivors of childhood cancer--an update.

Treatment-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) is a devastating complication of treatment for childhood cancer. However, the major cause of premature death of children treated for cancer remains their primary cancer. The understanding of the presentation, incidence, predisposing risk factors and pathobiology of t-MDS/t-AML is increasing. This increased understanding has not yet been translated into improved outcomes of therapy for t-MDS/t-AML. However, newer approaches are under study.

Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group.

Children with Down syndrome (DS) are highly susceptible to acute leukaemia. Given the potential role of infections in the aetiology of leukaemia in children without DS, we investigated whether there was an association between early-life infections and acute leukaemia in children with DS. Maternal infections during pregnancy were also examined. We enrolled 158 incident cases of acute leukaemia in children with DS (97 acute lymphoblastic leukaemia (ALL) and 61 acute myeloid leukaemia (AML)) diagnosed at Children's Oncology Group institutions between 1997 and 2002. DS controls (N=173) were selected from the cases' primary care clinics and frequency matched on age at leukaemia diagnosis. Data were collected on demographics, child's medical history, mother's medical history, and other factors by maternal interview. Analyses were conducted using unconditional logistic regression adjusted for potential confounders. A significant negative association was observed between acute leukaemia and any infection in the first 2 years of life (adjusted odds ratio (OR)=0.55, 95% confidence interval (CI) (0.33-0.92); OR=0.53, 95% CI (0.29-0.97); and OR=0.59, 95% CI (0.28-1.25) for acute leukaemia combined, ALL, and AML respectively). The association between acute leukaemia and maternal infections during pregnancy was in the same direction but not significant. This study offers support for the hypothesis that early-life infections may play a protective role in the aetiology of acute leukaemia in children with DS.

In vitro activity of expanded-spectrum pyridazinyl oxime ethers related to pirodavir: novel capsid-binding inhibitors with potent antipicornavirus activity.

Picornaviruses (PV) include human rhinovirus (HRV), the primary cause of the common cold, and the enteroviruses (EV), which cause serious diseases such as poliomyelitis, meningoencephalitis, and systemic neonatal disease. Although no compounds for PV infections have been approved in the United States, pirodavir was one of the most promising capsid-binding compounds to show efficacy in human clinical trials for chemoprophylaxis of the common cold. Susceptibility to hydrolysis precluded its use as an oral agent. We have developed orally bioavailable pyridazinyl oxime ethers that are as potent as pirodavir. Compounds BTA39 and BTA188 inhibited a total of 56 HRV laboratory strains and three clinical isolates as determined by neutral red uptake assay. At concentrations of <100 nM, BTA39 inhibited 69% of the HRV serotypes and isolates evaluated, BTA188 inhibited 75%, and pirodavir inhibited 59% of the serotypes and isolates. The 50% inhibitory concentrations (IC(50)s) for the two compounds ranged from 0.5 nM to 6,701 nM. The compounds also inhibited EV, including coxsackie A and B viruses (IC(50) = 773 to 3,608 nM) and echoviruses (IC(50) = 193 to 5,155 nM). BTA39 only inhibited poliovirus strain WM-1 at 204 nM, and BTA188 only inhibited poliovirus strain Chat at 82 nM. EV 71 was inhibited by BTA39 and BTA188, with IC(50)s of 1 and 82 nM, respectively. Both compounds were relatively nontoxic in actively growing cells (50% cytotoxic doses, >/=4,588 nM). These data suggest that these oxime ethers warrant further investigation as potential agents for treating selected PV infections.