CYP2B6*6 genotype specific differences in artemether‐lumefantrine disposition in healthy volunteers

Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of the antimalarial drugs artemether and lumefantrine. Here we investigated the effect of CYP2B6*6 on the plasma pharmacokinetics of artemether, lumefantrine, and their metabolites in healthy volunteers. Thirty healthy and previously genotyped adult volunteers—15 noncarriers (CYP2B6*1/*1) and 15 homozygote carriers (CYP2B6*6/*6)—selected from a cohort of 150 subjects from the Ilorin metropolitan area were administered the complete 3‐day course of artemether and lumefantrine (80 and 480 mg twice daily, respectively). Intensive pharmacokinetic sampling was conducted at different time points before and after the last dose. Plasma concentrations of artemether, lumefantrine, dihydroartemisinin, and desbutyllumefantrine were quantified using validated liquid chromatography–mass spectrometric methods. Pharmacokinetic parameters were evaluated using noncompartmental analysis. Artemether clearance of CYP2B6*6/*6 volunteers was nonsignificantly lower by 26% (ratios of geometric mean [90% CI]; 0.74 [0.52‐1.05]), and total exposure (the area under the plasma concentration‐time curve from time 0 to infinity [AUC0‐∞]) was greater by 35% (1.35 [0.95‐1.93]) when compared with those of *1/*1 volunteers. Similarly, assuming complete bioconversion from artemether, the dihydroartemisinin AUC0‐∞ was 22% lower. On the contrary, artemether‐to‐dihydroartemisinin AUC0‐∞ ratio was 73% significantly higher (1.73 [1.27‐2.37]). Comparison of lumefantrine exposure and lumefantrine‐to‐desbutyllumefantrine metabolic ratio of *6/*6 with corresponding data from *1/*1 volunteers showed no differences. The increased artemether‐to‐dihydroartemisinin metabolic ratio of *6/*6 volunteers is unlikely to result in differences in artemether‐lumefantrine efficacy and treatment outcomes. This is the first study in humans to associate CYP2B6*6 genotype with artemether disposition

Insights about Cannabis and Psychosis Using Video Games for Young People with a First Episode of Psychosis, Particularly Those from Black Racialized Communities: Protocol for a Mixed Methods Study

Background: Cannabis use disorder among young people with a first episode of psychosis contributes to relapse, hospitalization, and impaired functioning. However, few studies have examined what young people with early phase psychosis, particularly those from Black racialized communities, understand or appreciate about this relationship, even though they may be at risk. There are no formally tested knowledge translation strategies that disseminate these research findings for young people with emerging psychosis from Black racialized communities. Objective: This study aims to conceptualize what young people with early phase psychosis/cannabis use disorder understand about the relationship between cannabis and psychosis, focusing on people from racialized backgrounds. This study also aims to assess whether the knowledge translation product, the “Back to Reality Series,” increases awareness of the impact of cannabis use on psychosis from the perspectives of young people with emerging psychosis and cannabis use disorder from Black African and Caribbean communities. Methods: Qualitative analysis will reveal themes from qualitative interviews about cannabis and psychosis from the perspectives of young people with emerging psychosis and cannabis use disorder from Black African and Caribbean communities. Perceptions before and after exposure to the Back to Reality Series will be qualitatively analyzed. A control game will be used for comparison, and scores on a quiz after playing the Back to Reality Series will be quantitatively analyzed to establish whether the Back to Reality Series raises awareness of the effects of cannabis on psychosis. An advisory council involving young people from Black communities, family members, and clinicians will bring community perspectives to this research. Results: We began recruiting participants for this study in September 2021. We will complete data collection on demographic and clinical factors, qualitative interviews, and quantitative assessments of the Back to Reality Series. Conclusions: The voices of young people from racialized backgrounds will generate preliminary data to inform early psychosis programs, addressing cannabis use in this population. The findings may advance the use of a new knowledge translation product that deals with gaps in knowledge about cannabis use for people experiencing early phase psychosis, particularly those from racialized communities

Functioning in older adults with bipolar disorder: A report on recommendations by the International Society of bipolar disorder (ISBD) older adults with bipolar disorder (OABD) task force

Objectives: Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve the clinical outcomes of this population. Methods: Through a series of virtual meetings, experts from eight countries in the International Society of Bipolar Disorder (ISBD) on OABD task force developed recommendations for the assessment of psychosocial functioning. Results: We present (1) a conceptualization of functioning in OABD and differences compared with younger patients; (2) factors related to functioning in OABD; (3) current measures of functioning in OABD and their strengths and limitations; and, (4) other potential sources of information to assess functioning. Conclusions: The task force created recommendations for assessing functioning in OABD. Current instruments are limited, so measures specifically designed for OABD, such as the validated FAST-O scale, should be more widely adopted. Following the proposed recommendations for assessment can improve research and clinical care in OABD and potentially lead to better treatment outcomes

Functioning in older adults with bipolar disorder: A report on recommendations by the International Society of bipolar disorder (ISBD) older adults with bipolar disorder (OABD) task force

OBJECTIVES: Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve the clinical outcomes of this population. METHODS: Through a series of virtual meetings, experts from eight countries in the International Society of Bipolar Disorder (ISBD) on OABD task force developed recommendations for the assessment of psychosocial functioning. RESULTS: We present (1) a conceptualization of functioning in OABD and differences compared with younger patients; (2) factors related to functioning in OABD; (3) current measures of functioning in OABD and their strengths and limitations; and, (4) other potential sources of information to assess functioning. CONCLUSIONS: The task force created recommendations for assessing functioning in OABD. Current instruments are limited, so measures specifically designed for OABD, such as the validated FAST-O scale, should be more widely adopted. Following the proposed recommendations for assessment can improve research and clinical care in OABD and potentially lead to better treatment outcomes

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Global, regional, and national burden of tuberculosis, 1990–2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study

Background Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016. Methods We analysed 15 943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate. Findings Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9·02 million (95% uncertainty interval [UI] 8·05–10·16) and the number of tuberculosis deaths was 1·21 million (1·16–1·27). Among HIV-positive individuals, the number of incident cases was 1·40 million (1·01–1·89) and the number of tuberculosis deaths was 0·24 million (0·16–0·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (–1·3% [–1·5 to −1·2]) than mortality did (–4·5% [–5·0 to −4·1]) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was −4·0% (–4·5 to −3·7) and mortality was −8·9% (–9·5 to −8·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13·7 for incidence and 14·9 for mortality), and the lowest ratios were in high-income North America (0·4 for incidence) and Oceania (0·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67·3 for incidence and 73·0 for mortality), and high-income North America had the lowest ratios (0·4 for incidence and 0·5 for mortality). Interpretation If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV

A longitudinal cohort study of symptoms and other concerns among Nigerian people with stages 3–5 chronic kidney diseases: study protocol

Background: The burden of symptoms and other concerns in chronic kidney disease (CKD) is known to be high, adversely affecting the quality of life of the growing number of those with this condition in developing countries. In this paper, we describe the protocol of a longitudinal observational study among people living with CKD. The study is developed to assess the bio-psychosocial factors associated with palliative care symptoms and concerns, and pattern of health services usage among Nigerians with stages 3–5 CKD. The overall objective is to establish the evidence-base for advocacy and policy formulation, treatment guidelines, care and services, and future clinical trial studies.Methods: This is a multi-center study to investigate the longitudinal course of symptoms and other concerns among patients with stages 3–5 CKD in Nigeria. Interviewer administered and self-report measures at baseline (T0) and 3-month (T1) address socio-demographic characteristics, clinical-illness related information, palliative care-related symptoms and other concerns, pattern of formal or informal service usage, and bio psychosocial measures including estimated glomerular filtration rate (eGFR), anxiety, depression, quality of life, functioning, social support and spiritual wellbeing.Discussion: This study represents the first longitudinal investigation of palliative care symptoms and concerns among people with CKD in Nigeria. It includes early stages of CKD in compliance with best practices, and a comprehensive range of bio-psychosocial outcomes to understand how these factors are associated with symptoms. This study will provide evidence for how best to integrate palliative care into management of CKD to improve care and quality of life of people with CKD. The study team welcomes collaborations with both national and international researchers