Identifying determinants of HIV disease progression in Saskatoon, Saskatchewan

Context & Rationale: Individuals with similar CD4 cell counts and RNA levels can vary considerably with regards to clinical progression. This variation is likely the result of a complex interplay between viral, host and environmental factors. This study aimed to characterize and identify predictors associated with disease progression to AIDS or death in Saskatoon, Saskatchewan. Methods: This is a retrospective cohort study of 343 seroprevalent HIV positive patients diagnosed from Jan 2005 to Dec 2010. Of these, 73 had an estimated seroconversion date. Data was extracted from medical charts at two clinics specialized in HIV/AIDS care. Disease progression was measured as time from HIV diagnosis (or seroconversion) to immunological AIDS and death. The Cox hazard model was used. Results: The 3-year and 5-year immunological AIDS free probability was 53% and 33%, respectively. The 3-year and 5-year survival probability was 89% and 77%, respectively. Among the seroconversion cohort, the 3-year immunological AIDS free probability was 76%. Due to multicollinearity, separate models were built for IDU, hepatitis C and ethnicity. A history of IDU (HR, 3.0; 95%CI, 1.2-7.1), hepatitis C coinfection (HR, 2.9; 95%CI, 1.2-6.9), baseline CD4 counts (HR, 0.95; 95%CI, 0.92-0.98, per ever 10 unit increase), ever on ART, and year of diagnosis were significant predictors of progression to immunological AIDS among the seroprevalent cohort. Age at diagnosis, sex and ethnicity were not. For survival, only treatment use was a significant predictor (HR, 0.34; 95%CI, 0.1-0.8). Hepatitis C coinfection was marginally significant (p=0.067), while a history of IDU, ethnicity, gender, age at diagnosis, and year of diagnosis were not. Among the seroconversion cohort, no predictors of progression to immunological AIDS were identified. Ethnicity, hepatitis C coinfection and history of IDU could not be assessed. Conclusion: Our study found that IDU, HCV coinfections, baseline CD4 counts, and ART use were significant predictors of disease progression. This highlights the need for increased testing and early detection and for targeted interventions for these particularly vulnerable populations to slow disease progression

Effectiveness of Home Visiting Programs on Child Outcomes: A Systematic Review

http://www.biomedcentral.com/1471-2458/13/17Background: The effectiveness of paraprofessional home-visitations on improving the circumstances of disadvantaged families is unclear. The purpose of this paper is to systematically review the effectiveness of paraprofessional home-visiting programs on developmental and health outcomes of young children from disadvantaged families. Methods: A comprehensive search of electronic databases (e.g., CINAHL PLUS, Cochrane, EMBASE, MEDLINE) from1990 through May 2012 was supplemented by reference lists to search for relevant studies. Through the use of reliable tools, studies were assessed in duplicate. English language studies of paraprofessional home-visiting programs assessing specific outcomes for children (0-6 years) from disadvantaged families were eligible for inclusion in the review. Data extraction included the characteristics of the participants, intervention, outcomes and quality of the studies. Results: Studies that scored 13 or greater out of a total of 15 on the validity tool (n = 21) are the focus of this review. All studies are randomized controlled trials and most were conducted in the United States. Significant improvements to the development and health of young children as a result of a home-visiting program are noted for particular groups. These include: (a) prevention of child abuse in some cases, particularly when the intervention is initiated prenatally; (b) developmental benefits in relation to cognition and problem behaviours, and less consistently with language skills; and (c) reduced incidence of low birth weights and health problems in older children, and increased incidence of appropriate weight gain in early childhood. However, overall home-visiting programs are limited in improving the lives of socially high-risk children who live in disadvantaged families. Conclusions: Home visitation by paraprofessionals is an intervention that holds promise for socially high-risk families with young children. Initiating the intervention prenatally and increasing the number of visits improves development and health outcomes for particular groups of children. Future studies should consider what dose of the intervention is most beneficial and address retention issues.</p

Differences in Rate of Perceived Exertion and Workload Intensity in Males and Females during Submaximal Arm and Leg Ergometry

International Journal of Exercise Science 15(4): 1222-1235, 2022. Purpose: Arm ergometry (AE) is necessitated for individuals unable to perform leg ergometry (LE) exercise. This study explored gender differences in RPE and workload (WL) during AE and LE at submaximal target heart rates (THR). Methods: 35 healthy college-aged individuals were randomly allocated to begin exercise on either AE or LE. Participants exercised on both modes with increasing WL to achieve submaximal THRs of 110, 120, 130, 140 and 150 beats per minute (bpm). Factorial ANOVAs tested for differences in RPE and WL. Results: No significant differences were found in RPE between genders, as well as between arm and leg exercise (p \u3e 0.001). For WL, a significant main effect was found for mode with LE greater than AE (p \u3c 0.001), and gender, with males greater than females (p \u3c 0.001). A significant interaction effect was also found for HR and mode, with a greater increase in WL during LE compared to AE in both genders (p = 0.001). Conclusions: Exercise specialists typically prescribe exercise based on a chosen THR. The results of this study provide meaningful data on mean RPE and WL responses that a given THR elicits for ergometry. The finding of no differences in RPE between AE and LE informs the clinician that at any given submaximal THR, similar RPE scores can be expected during AE and LE. Further research is warranted to investigate differences in wider populations

County-level hurricane exposure and birth rates: application of difference-in-differences analysis for confounding control

Abstract Background Epidemiological analyses of aggregated data are often used to evaluate theoretical health effects of natural disasters. Such analyses are susceptible to confounding by unmeasured differences between the exposed and unexposed populations. To demonstrate the difference-in-difference method our population included all recorded Florida live births that reached 20 weeks gestation and conceived after the first hurricane of 2004 or in 2003 (when no hurricanes made landfall). Hurricane exposure was categorized using ≥74 mile per hour hurricane wind speed as well as a 60 km spatial buffer based on weather data from the National Oceanic and Atmospheric Administration. The effect of exposure was quantified as live birth rate differences and 95 % confidence intervals [RD (95 % CI)]. To illustrate sensitivity of the results, the difference-in-differences estimates were compared to general linear models adjusted for census-level covariates. This analysis demonstrates difference-in-differences as a method to control for time-invariant confounders investigating hurricane exposure on live birth rates. Results Difference-in-differences analysis yielded consistently null associations across exposure metrics and hurricanes for the post hurricane rate difference between exposed and unexposed areas (e.g., Hurricane Ivan for 60 km spatial buffer [−0.02 births/1000 individuals (−0.51, 0.47)]. In contrast, general linear models suggested a positive association between hurricane exposure and birth rate [Hurricane Ivan for 60 km spatial buffer (2.80 births/1000 individuals (1.94, 3.67)] but not all models. Conclusions Ecological studies of associations between environmental exposures and health are susceptible to confounding due to unmeasured population attributes. Here we demonstrate an accessible method of control for time-invariant confounders for future research

Differential Role of gp130-Dependent STAT and Ras Signalling for Haematopoiesis Following Bone-Marrow Transplantation

INTRODUCTION: Bone marrow transplantation (BMT) is a complex process regulated by different cytokines and growth factors. The pleiotropic cytokine IL-6 (Interleukin-6) and related cytokines of the same family acting on the common signal transducer gp130 are known to play a key role in bone marrow (BM) engraftment. In contrast, the exact signalling events that control IL-6/gp130-driven haematopoietic stem cell development during BMT remain unresolved. METHODS: Conditional gp130 knockout and knockin mice were used to delete gp130 expression (gp130(ΔMx)), or to selectively disrupt gp130-dependent Ras (gp130(ΔMxRas)) or STAT signalling (gp130(ΔMxSTAT)) in BM cells. BM derived from the respective strains was transplanted into irradiated wildtype hosts and repopulation of various haematopoietic lineages was monitored by flow cytometry. RESULTS: BM derived from gp130 deficient donor mice (gp130(ΔMx)) displayed a delayed engraftment, as evidenced by reduced total white blood cells (WBC), marked thrombocytopenia and anaemia in the early phase after BMT. Lineage analysis unravelled a restricted development of CD4(+) and CD8(+) T-cells, CD19(+) B-cells and CD11b(+) myeloid cells after transplantation of gp130-deficient BM grafts. To further delineate the two major gp130-induced signalling cascades, Ras-MAPK and STAT1/3-signalling respectively, we used gp130(ΔMxRas) and gp130(ΔMxSTAT) donor BM. BMT of gp130(ΔMxSTAT) cells significantly impaired engraftment of CD4(+), CD8(+), CD19(+) and CD11b(+) cells, whereas gp130(ΔMxRas) BM displayed a selective impairment in early thrombopoiesis. Importantly, gp130-STAT1/3 signalling deficiency in BM grafts severely impaired survival of transplanted mice, thus demonstrating a pivotal role for this pathway in BM graft survival and function. CONCLUSION: Our data unravel a vital function of IL-6/gp130-STAT1/3 signals for BM engraftment and haematopoiesis, as well as for host survival after transplantation. STAT1/3 and ras-dependent pathways thereby exert distinct functions on individual bone-marrow-lineages

Characteristics of gay, bisexual and other men who have sex with men with multiple diagnoses of infectious syphilis in British Columbia, Canada, 2005-2014

Background: Infectious syphilis has increased substantially over the past decade. Targeting limited public health resources toward subpopulations with multiple reinfections may have a large impact in reducing onward transmission within a community. Methods: A chart review was conducted for individuals with 4 or more infectious syphilis diagnoses between 2005 and 2014 (the top 1% of all syphilis diagnoses in British Columbia, Canada). We characterized the sociodemographics, partner notification outcomes and social network. Results: Between 2005 and 2014, there were 30 individuals with 4 or more syphilis diagnoses, accounting for 139 diagnoses. All were men who have sex with men and 29 (96%) were human immunodeficiency virus–positive. Of the 139 diagnoses, 65% occurred in the early latent stage of infection, 22% in the secondary stage, and 14% in the primary stage. The median number of sexual partners per diagnosis was 5 (range, 1–50). Among the 838 partners reported, 79% were notifiable, 53% were notified, and 23% were reported to be tested or treated. Sexual network mapping showed that almost half of the members of this group could be linked to one another either directly or indirectly via partners over 10 years. Social network mapping demonstrated high connectivity, with 4 venues associated with almost two thirds of the study population. Conclusions: The connectivity and recurrent diagnoses in this study population suggest potential benefits of targeted interventions to individuals with multiple diagnoses and their partners. Our study highlights the need for enhanced care, increased syphilis testing frequency, and exploring alternative preventative methods among individuals with syphilis rediagnoses to reduce syphilis incidence

Hemodynamic evaluation of anesthetized baboons and piglets by transpulmonary thermodilution: Normal values and interspecies differences with respect to xenotransplantation

Background Transpulmonary thermodilution is well established as a tool for in-depth hemodynamic monitoring of critically ill patients during surgical procedures and intensive care. It permits easy assessment of graft function following cardiac transplantation and guides post-operative volume and catecholamine therapy. Since no pulmonary catheter is needed, transpulmonary thermodilution could be useful in experimental cardiac pig-to-baboon xenotransplantation. However, normal values for healthy animals have not yet been reported. Here, we present data from piglets and baboons before xenotransplantation experiments and highlight differences between the two species and human reference values. Methods Transpulmonary thermodilution from baboons (body weight 10-34 kg) and piglets (body weight 10-38kg) were analyzed. Measurements were taken in steady state after induction of general anesthesia before surgical procedures commenced. Cardiac index (CI), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), parameters quantifying cardiac filling (global end-diastolic volume index, GEDI), and pulmonary edema (extravascular lung water, ELWI) were assessed. Results Preload, afterload, and contractility parameters clearly correlated with total body weight or body surface area. Baboons had lower CI values than weight-matched piglets (4.2 +/- 0.9l/min/m(2) vs 5.3 +/- 1.0/min/m(2), P < .01). MAP and SVRI were higher in baboons than piglets (MAP: 99 +/- 22 mm Hg vs 62 +/- 11 mm Hg, P < .01;SVRI: 1823 +/- 581 dyn*s/cm(5)*m(2) vs 827 +/- 204 dyn*s/cm(5)*m(2), P < .01). GEDI and ELWI did differ significantly between both species, but measurements were within similar ranges (GEDI: 523 +/- 103 mL/m(2) vs 433 +/- 78 mL/m(2), P < .01;ELWI: 10 +/- 3 mL/kg vs 11 +/- 2 mL/kg, P < .01). Regarding adult human reference values, CI was similar to both baboons and piglets, but all other parameters were different. Conclusions Parameters of preload, afterload, and contractility differ between baboons and piglets. In particular, baboons have a much higher afterload than piglets, which might be instrumental in causing perioperative xenograft dysfunction and post-operative myocardial hypertrophy after orthotopic pig-to-baboon cardiac xenotransplantation. Most transpulmonary thermodilution-derived parameters obtained from healthy piglets and baboons lie outside the reference ranges for humans, so human normal values should not be used to guide treatment in those animals. Our data provide reference values as a basis for developing algorithms for perioperative hemodynamic management in pig-to-baboon cardiac xenotransplantation