Temporal trends in disparities in COVID-19 seropositivity among Canadian blood donors.

BACKGROUND: In Canada's largest COVID-19 serological study, SARS-CoV-2 antibodies in blood donors have been monitored since 2020. No study has analysed changes in the association between anti-N seropositivity (a marker of recent infection) and geographic and sociodemographic characteristics over the pandemic. METHODS: Using Bayesian multi-level models with spatial effects at the census division level, we analysed changes in correlates of SARS-CoV-2 anti-N seropositivity across three periods in which different variants predominated (pre-Delta, Delta and Omicron). We analysed disparities by geographic area, individual traits (age, sex, race) and neighbourhood factors (urbanicity, material deprivation and social deprivation). Data were from 420 319 blood donations across four regions (Ontario, British Columbia [BC], the Prairies and the Atlantic region) from December 2020 to November 2022. RESULTS: Seropositivity was higher for racialized minorities, males and individuals in more materially deprived neighbourhoods in the pre-Delta and Delta waves. These subgroup differences dissipated in the Omicron wave as large swaths of the population became infected. Across all waves, seropositivity was higher in younger individuals and those with lower neighbourhood social deprivation. Rural residents had high seropositivity in the Prairies, but not other regions. Compared to generalized linear models, multi-level models with spatial effects had better fit and lower error when predicting SARS-CoV-2 anti-N seropositivity by geographic region. CONCLUSIONS: Correlates of recent COVID-19 infection have evolved over the pandemic. Many disparities lessened during the Omicron wave, but public health intervention may be warranted to address persistently higher burden among young people and those with less social deprivation.

High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial.

BACKGROUND: Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT. METHODS: This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active). FINDINGS: Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (-7·8% [95% CI -13·6 to -2·0]) and the 30 mg/kg group (-15·4% [-21·4 to -9·4]) than in the standard-dose group. INTERPRETATION: In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. FUNDING: Canadian Institutes of Health Research.

Ethnobotanical survey of medicinal plants used to manage High Blood Pressure and Type 2 Diabetes Mellitus in Bitterfontein, Western Cape Province, South Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this study was to identify and document medicinal plants used to manage High Blood Pressure and Type 2 Diabetes Mellitus in Bitterfontein, Western Cape Province, South Africa. METHODS: One hundred and twelve (112) respondents were interviewed between August 2014 and September 2015 through semi-structured surveys to gather data on the percentage of people who had been diagnosed with High Blood Pressure and/or Type 2 Diabetes Mellitus and to determine the frequency of medicinal plant and allopathic medicine use. Twelve (12) key respondents were subsequently selected, using a non-probability snowball sampling method. They were interviewed in-depth concerning their plant practices and assisted with plant collection. RESULTS: Twenty-four plant (24) species belonging to 15 families were identified for the management of High Blood Pressure and Type 2 Diabetes Mellitus. The most frequently reported families were Asteraceae (20.8%), Lamiaceae (16.67%), Crassulaceae (8.33%) and Aizoaceae (8.33%). The remaining (45.54%) were evenly split over eleven families- Fabaceae, Amaryllidaceae, Anacardiaceae, Capparaceae, Geraniaceae, Apiaceae, Convolvulaceae, Apocynaceae, Rutaceae, Asphodelaceae and Thymelaeaceae. The most commonly used plant species overall was Lessertia frutescens (96.55%). The most frequently used plant parts included leaves (57.63%) roots/bulbs (15.25%) and stems (11.86%), mostly prepared as infusions or decoctions for oral administration. CONCLUSIONS: Medicinal plants are widely used by High Blood Pressure and Type 2 Diabetes Mellitus sufferers. They employ diverse plant species to manage both conditions. In addition, some sufferers often use prescribed allopathic medication, as well as medicinal plants, but at different intervals. Despite high usage the plants identified are not currently threatened (Red Data list status: least concern).

Tulbaghia--A Southern African Phytomedicine.

The phytomedicine Tulbaghia consists of the fresh or dried subterranean organs of various Tulbaghia species. The genus is endemic to Southern Africa and includes about 20 species, of which only T. alliacea and T. capensis are naturally found in the winter rainfall climate area (the Western Cape). The genus forms part of the Alliaceae family and is a geophyte (plants with an underground perennation organ and leaves that die back annually). Their habitat can range from semi-desert to wet and boggy terrain. Wild garlic is most commonly prepared as an infusion or boiled in water and taken orally. Externally, as a medicated bath, wild garlic is used to treat paralysis and rheumatism and to reduce the temperature in a feverish patient. Internally, rhizome or bulb preparations are taken orally to treat fever; as a remedy for colds and influenza, asthma, tuberculosis, and stomach problems; as an antihypertensive; or to expel intestinal worms. It is also used as a prophylactic against winter infections. Rhizome pieces are often placed in castor oil to make eardrops. For fever and high blood pressure, a tea is made from the bulbs or rhizomes and a small cup taken three times daily. The leaves of the plant are used to treat esophageal cancer and may also be eaten as a vegetable. The demand for Tulbaghia in both formal and informal markets has grown exponentially. Sustainable harvesting focuses on only harvesting enough of the plant so that it still has the capacity for self-renewal. However, because both the above-ground and underground parts of Tulbaghia are commonly used in African traditional medicine, destructive harvesting of the whole plant is inevitable, thus necessitating the large-scale organized propagation of these plants. It is therefore important to establish a new strategy for the sustainable harvesting of these plants as commercial crops.

Traditional health practitioners' perceptions, herbal treatment and management of HIV and related opportunistic infections.

BACKGROUND: In South Africa, traditional health practitioners' (THPs) explanatory frameworks concerning illness aetiologies are much researched. However there is a gap in the literature on how THPs understand HIV-related opportunistic infections (OIs), i.e. tuberculosis, candidiasis and herpes zoster. This study aimed to comprehend THPs' understandings of the aforementioned; to ascertain and better understand the treatment methods used by THPs for HIV and OIs, while also contributing to the documentation of South African medicinal plants for future conservation. METHODS: The study was conducted in two locations: Strand, Western Cape where THPs are trained and Mpoza village, Mount Frere, Eastern Cape from where medicinal plants are ordered or collected. Semi-structured interviews were conducted with 53 THPs of whom 36 were diviners (amagrirha: isangoma) and 17 herbalists (inyanga). THPs were selected through a non-probability "snowball" method. Data were analysed using a thematic content analysis approach. An ethnobotanical survey was conducted and plants used to manage HIV and OIs were collected. A complete set of voucher specimens was deposited at the University of the Western Cape Herbarium for identification. Plant names were checked and updated with Kew's online website http://www.theplantlist.org . RESULTS: THPs conceptualise the aetiology of HIV and OIs at two related levels. The first involves the immediate manifestation of the illness/condition because of a viral infection in the blood (HIV), the presence of bacteria in the lungs (tuberculosis), or weakened state of the body making it susceptible to OIs. The presence of OIs is indicative of the probable presence of HIV. The second level of causation affects the first, which includes pollution, changes in cultural sexual norms, witchcraft, environmental factors, and lack of adherence to ancestral rituals. THPs reported using 17 plants belonging to 12 families. Remedies included mixes of up to five plants. CONCLUSION: This study explored the THPs' perspectives on HIV and commonly associated OIs and their herbal treatment methods. THPs generally rely on biomedical diagnosis before treating a client. They also seek guidance from the ancestors for a particular diagnosis, the plants to use for a specific treatment, when to harvest, and how to administer herbal remedies.

A Phase I study of pazopanib in combination with gemcitabine in patients with advanced solid tumors.

PURPOSE: Pazopanib plus gemcitabine combination therapy was explored in patients with advanced solid tumors. METHODS: In a modified 3 + 3 enrollment scheme, oral once-daily pazopanib was administered with intravenous gemcitabine (Days 1 and 8, 21-day cycles). Three protocol-specified dose levels were tested: pazopanib 400 mg plus gemcitabine 1,000 mg/m(2), pazopanib 800 mg plus gemcitabine 1,000 mg/m(2), and pazopanib 800 mg plus gemcitabine 1,250 mg/m(2). Maximum-tolerated dose was based on dose-limiting toxicities during treatment Cycle 1. In the expansion phase, six additional patients were enrolled at the highest tolerable dose level. RESULTS: Twenty-two patients were enrolled. At the highest dose level tested (pazopanib 800 plus gemcitabine 1,250), patients received >80% of their planned dose and the regimen was deemed safe and tolerable. The most common treatment-related adverse events included fatigue, neutropenia, nausea, and decreased appetite. Neutropenia and thrombocytopenia were the most common events leading to dose modifications. Pharmacokinetic interaction between pazopanib and gemcitabine was not observed. One objective partial response at the highest dose was observed in a patient with metastatic melanoma. Prolonged disease stabilization (>12 cycles) was reported in three patients (metastatic melanoma, cholangiocarcinoma, and colorectal carcinoma). CONCLUSION: Combination pazopanib plus gemcitabine therapy is tolerable, with an adverse event profile reflective of that associated with the individual agents. There was no apparent pharmacokinetic interaction with pazopanib plus gemcitabine co-administration, although patient numbers were limited. Further investigation of combined pazopanib plus gemcitabine is warranted.

Can Canada afford a truly pan-Canadian approach to elder care?

This commentary is about Canada's ability to afford a comprehensive pan-Canadian approach to elder care. In redefining the universal public system, a broad and more comprehensive definition of universal public care is needed for those whose physical or mental abilities are impaired. The Scandinavian model affirms that this is both effective and affordable. Comparisons of Canada with other nations in the Organisation for Economic Co-operation and Development on taxation and spending levels reveal that there is room for Canada to increase taxation to fund a Scandinavian model while still having competitive tax and spending rates.

Phase I trial of pazopanib in patients with advanced cancer.

PURPOSE: The safety, pharmacokinetics, and clinical activity of pazopanib (GW786034), an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit, were evaluated in patients with advanced-stage refractory solid tumors. EXPERIMENTAL DESIGN: Patients were enrolled into sequential dose-escalating cohorts (50 mg three times weekly to 2,000 mg once daily and 300-400 mg twice daily). Escalation or deescalation was based on toxicities observed in the preceding dose cohort. Pharmacokinetic and biomarker samples were obtained. Clinical response was assessed every 9 weeks. RESULTS: Sixty-three patients were treated (dose escalation, n = 43; dose expansion, n = 20). Hypertension, diarrhea, hair depigmentation, and nausea were the most frequent drug-related adverse events, the majority of which were of grade 1/2. Hypertension was the most frequent grade 3 adverse event. Four patients experienced dose-limiting toxicities at 50 mg, 800 mg, and 2,000 mg once daily. A plateau in steady-state exposure was observed at doses of >or=800 mg once daily. The mean elimination half-life at this dose was 31.1 hours. A mean target trough concentration (C(24)) >or=15 microg/mL (34 micromol/L) was achieved at 800 mg once daily. Three patients had partial responses (two confirmed, one unconfirmed), and stable disease of >or=6 months was observed in 14 patients; clinical benefit was generally observed in patients who received doses of >or=800 mg once daily or 300 mg twice daily. CONCLUSION: Pazopanib was generally well tolerated and showed antitumor activity across various tumor types. A monotherapy dose of 800 mg once daily was selected for phase II studies.

Impact of post-abortion family planning services on contraceptive use and abortion rate among young women in China: a cluster randomised trial.

OBJECTIVES: To compare two post-abortion family planning (FP) service packages on contraceptive use and repeat abortion rate among young women in three cities in China. METHODS: In this cluster-randomized trial, one FP service package included provision of limited information and referral to existing FP services, and the other, more comprehensive, package consisted--in addition to the above simple package--of individual counselling, free provision of contraceptive materials, and involvement of the male partner. Eight matched pairs of hospitals were certified by centralized randomization. Women undergoing abortion were followed up for six months, and data were collected in two rounds, before and after the intervention. RESULTS: We followed a total of 2336 women younger than 25 years (555 before and 555 after the simple intervention package; 634 before and 592 after the comprehensive intervention package). Both packages increased use of any contraceptive method, but the comprehensive approach also increased use of more effective methods. Odds ratios for consistent and correct use of condoms were 2.32 (95% confidence interval 1.55-3.46) and 2.78 (1.81-4.26), respectively, compared with the simple package. The rates of unwanted pregnancies and repeat abortions were somewhat reduced for both packages, with no significant statistical difference between them. CONCLUSION: Couples who received the comprehensive post-abortion FP service appear to use more effective contraceptive methods and show better compliance.

The need for integrating family planning and postabortion care in China.

OBJECTIVE: To assess the need for integrating postabortion care with family planning services in China. METHOD: We collected data from a clinic-based study of 24 abortion clinics in 3 large cities in China. RESULTS: There was a total of 287 (10.3%) high-risk abortions among the 2780 respondents, 974 (35%) of whom had had repeated abortions and 48.4% had had 2 abortions within 1 year; 63.7% of the current pregnancies resulted from not using contraceptives; 28.8% and 19.8% of these new pregnancies, respectively, were due to the failure of the rhythm or the withdrawal method; only 9.7% of the respondents consistently used condoms; and only 9.1% could identify the correct time of their first ovulation following an abortion. CONCLUSION: Contraceptive neglect and the high rates of repeated and high-risk abortions call for the integration of postabortion care with family planning services in China.

Understanding diversity in impact and responses among HIV/AIDS-affected households: the case of Msinga, South Africa.

To gain a more comprehensive understanding of the impact of HIV and AIDS on rural households in Msinga, South Africa, the sustainable livelihoods framework was adapted. An ethnographic perspective was employed to examine: 1) the impact of HIV/AIDS-related illnesses on people's mind and spirit (the internal environment), and 2) the influence of institutional structures and processes (the external environment), in order to better understand 3) the actions taken by individuals and households in response to HIV and AIDS. Members of three support groups at a local drop-in centre were consulted about the impact of HIV and AIDS on their lives through focus groups, a questionnaire and in-depth interviews. The study shows that the psychosocial impact and associated coping strategies, as well as prevailing gender-based power relations and exclusion from social-exchange networks - which are not (readily) available factors in the sustainable livelihoods framework - affect people's lives in different ways and depend on the specific situation of the individual or household concerned. The study confirms the need to restore a household's resource base and to address psychosocial issues. However, the variation in impact to different households requires a diversified and holistic programme of development interventions.

The gaps in the gaze in South African hospitals.

Analysis of health care systems, especially hospitals, could benefit from Foucault's description of the medical gaze and the panopticon. Foucault's perspective sheds new light on the South African transformation from an oppressive to a more democratic State and is played out in particular ways in hospital settings. Analyses of the South African health care system and its interface with patients in hospitals seldom draw on the work of Foucault, despite its pertinent description of the diffuse and insidious forms of social surveillance (the 'gaze') and processes of 'normalization' brought about in panoptical settings. The gaze has become a metaphor for the processes whereby disciplinary 'technologies', together with the emergence of a normative social science, discipline both the mind and body of the individual, as in my example of a medicalised institutional setting. Transformation from an oppressive State system to a democratic South Africa has impacted in particular ways on the hospital setting. Instead of being subject to the constant surveillance of the gaze of the State or of medicine, there are numerous instances where patients to all intents become 'invisible', and end up beyond its perimeters. In the hospital, as in the heterogeneous South African community, there is a continuous process of adjustment, with patients, services and staff being rotated in an attempt to provide redress and equal access to health services for all. A large, long-standing lack of funds forces the medical staff to make decisions as to who should get access to beds and to optimal care, and this permeates the everyday experience of institutionalisation and care-giving. It also militates against neutral policy objectives, consistent surveillance or a homogenised system of care.

Community violence and PTSD in selected South African townships.

Given the high rates of crime in South Africa's townships, nonpolitical violence out-side the home and its psychological impact on women were investigated within two samples, the primary a help-seeking sample and the secondary a community sample. In the help-seeking sample, two thirds of the women reported having experienced several traumatic events outside the home. Those women displayed a median of 9 PTSD (post-traumatic stress disorder) symptoms, with nearly half meeting all criteria for PTSD. In the community sample, 40 women of color were interviewed at a community festival for women, and again two thirds reported having experienced several traumatic events outside the home during the previous year. These women displayed a median of 8.8 PTSD symptoms, with none meeting all criteria for PTSD. South Africa's distinctive culture of violence is discussed as context for understanding issues of community violence and PTSD among women in its minority townships.