Regional adiposity and insulin sensitivity - interactions with menopause and HIV in middle-aged Black African women.

OBJECTIVE: To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women. METHODS: Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative (n = 21); premenopausal women living with HIV (WLWH; n = 11); postmenopausal HIV-negative (n = 42); postmenopausal WLWH (n = 18) underwent the following tests: body composition (dual energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size and mRNA expression of adipokines, inflammation, and estrogen receptors [ER]. RESULTS: Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status. Pooled analysis showed significant models for SI (P = 0.002) and DI (P = 0.003). Higher SI was associated with lower leptin and CD11c expression in aSAT and higher adiponectin in gSAT. Higher DI was associated with higher aSAT and gSAT expression of adiponectin, LPL, ERα, and PPARγ, and lower leptin in aSAT. WLWH had higher expression of adiponectin and lower expression of leptin in both aSAT (P = 0.002 and P = 0.005) and gSAT (P = 0.004 and P = 0.002), respectively, and a larger proportion of smaller cells in aSAT (P < 0.001). CONCLUSION: Insulin sensitivity and beta cell function were distinctively associated with aSAT and gSAT. While menopause did not influence these relationships, HIV had a significant effect on adipose tissue, characterised by variations in cell size distribution and transcript levels within the depots.

Coprevalence and associations of diabetes mellitus and hypertension among people living with HIV/AIDS in Cameroon.

BACKGROUND: The association between HIV infection and increased cardiometabolic risk, attributed to chronic inflammation in people living with HIV (PLWH) and/or antiretroviral therapy (ART) effects, has been inconsistent. In this study, we aimed to assess the associations of HIV-related factors with hypertension (HTN) and type-2 diabetes mellitus (T2DM), and the potential mediation effects of body mass index (BMI) in the associations between ART use and HTN or T2DM in PLWH in Cameroon. METHODS: A cross-sectional study was conducted with 14,119 adult PLWH from Cameroon enrolled in the International epidemiology Databases to Evaluate AIDS (IeDEA) between 2016 and 2021. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg and/or current use of antihypertensive medication, while T2DM was defined as fasting blood sugar ≥ 126 mg/dL and/or use of antidiabetic medications. Univariable and multivariable multinomial logistic regression analyses examined the associations of factors with HTN alone, T2DM alone, and both (HTN + T2DM). Mediation analyses were conducted to assess the potential mediation roles of BMI, while controlling for age, sex, and smoking. RESULTS: Of the 14,119 participants, 9177 (65%) were women, with a median age of 42 (25th-75th percentiles: 35-51) years. Age > 50 years was associated with HTN alone, T2DM alone, and HTN + T2DM compared to the age group 19-29 years. Men had higher odds of having HTN + T2DM. Overweight and obesity were predictors of HTN alone compared to being underweight. WHO stages II and III HIV disease were inversely associated with HTN alone compared to stage I. The odds of diabetes alone were lower with ART use. BMI partially mediated the association between ART use and hypertension, with a proportion of mediation effect of 49.6% (all p < 0.02). However, BMI did not mediate the relationship between ART use and diabetes. CONCLUSIONS: Traditional cardiovascular risk factors were strongly associated with hypertension among PLWH, while HIV-related exposures had smaller associations. BMI partially mediated the association between ART use and hypertension. This study emphasizes the importance of screening, monitoring, and managing HTN and T2DM in older, male, and overweight/obese PLWH. Further research on the associations of HIV disease stage and ART use with HTN and T2DM is warranted.

Pre-Therapeutic Assessment of Older People in Sub-Saharan Africa: Introduction to the Comprehensive Geriatric Assessment.

Objectives: With the ongoing epidemiological transition in sub-Saharan Africa (SSA), conditions that require invasive treatment (surgery, cancer, and anaesthesia, etc.) will become increasingly common. Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic process aimed at identifying older people at risk of negative outcomes. It is important to know whether this approach integrates care management strategies for older people in a context where health services for older people are scarce, and staff members have little training in geriatrics. The current work is a situational analysis on the use of CGA on invasive care (cancer, surgery, etc.) among older people in SSA. Methods: We searched PubMed-MEDLINE and other sources for studies reporting on CGA and conditions requiring invasive treatment in older patients in SSA. Results/Conclusions: We found no study that had comprehensively examined CGA and invasive care in SSA. There is, however, evidence that the offer of invasive care to older people has improved in SSA. Further research is needed to explore the applicability of CGA in SSA. Similarly, more investigations are needed on the role of CGA in the care trajectories of older people in SSA, in terms of outcomes and affordability.

World Heart Federation Roadmap for Secondary Prevention of Cardiovascular Disease: 2023 Update.

Background: Secondary prevention lifestyle and pharmacological treatment of atherosclerotic cardiovascular disease (ASCVD) reduce a high proportion of recurrent events and mortality. However, significant gaps exist between guideline recommendations and usual clinical practice. Objectives: Describe the state of the art, the roadblocks, and successful strategies to overcome them in ASCVD secondary prevention management. Methods: A writing group reviewed guidelines and research papers and received inputs from an international committee composed of cardiovascular prevention and health systems experts about the article's structure, content, and draft. Finally, an external expert group reviewed the paper. Results: Smoking cessation, physical activity, diet and weight management, antiplatelets, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and cardiac rehabilitation reduce events and mortality. Potential roadblocks may occur at the individual, healthcare provider, and health system levels and include lack of access to healthcare and medicines, clinical inertia, lack of primary care infrastructure or built environments that support preventive cardiovascular health behaviours. Possible solutions include improving health literacy, self-management strategies, national policies to improve lifestyle and access to secondary prevention medication (including fix-dose combination therapy), implementing rehabilitation programs, and incorporating digital health interventions. Digital tools are being examined in a range of settings from enhancing self-management, risk factor control, and cardiac rehab. Conclusions: Effective strategies for secondary prevention management exist, but there are barriers to their implementation. WHF roadmaps can facilitate the development of a strategic plan to identify and implement local and national level approaches for improving secondary prevention.

Research for Health Care and Policy on HIV/AIDS: proceedings of the third edition of the Cameroon HIV Research (CAM-HERO) 2022, Kribi, Cameroon, from 1st to 3rd December 2022.

Cameroon is committed to reaching HIV epidemic control through coordinated efforts by the Ministry of Public Health, the National AIDS Control Committee, bilateral/multilateral institutions and implementing partners. The third edition of the Cameroon HIV Research Forum (CAM-HERO) was held in Kribi from December 1st to 3rd, 2022, with the theme "Research for Health Care and Policy on HIV/AIDS." The conference brought together local and international scientists and clinicians, policymakers, and regulatory authorities to 1) disseminate HIV research findings and HIV policy; 2) foster operational research collaboration; 3) build research capacity through training on basics of research methods and CAM-HERO young investigator Awards; and 4) initiate a guideline for promoting HIV/AIDS research in Cameroon. The main activities included training on research methodology and basic principles in bioethics, presentations of selected abstracts, and awards for top research. A total of 35 abstracts (16 oral presentations, 16 posters, and 3 late-breaker-abstracts) were selected for presentation following a rigorous review. The conference ended with evidence-based recommendations and a way-forward statement for the development of a National Guide for HIV/AIDS research in Cameroon, with the aim of improving the quality and quantity of research agenda and projects nationwide.

Uncontrolled Hypertension, Treatment, and Predictors among Hypertensive Out-Patients Attending Primary Health Facilities in Johannesburg, South Africa.

Hypertension is a poorly controlled risk factor for cardiovascular disease in South Africa, particularly among patients receiving care in the public sector who are mostly from low socioeconomic backgrounds. This cross-sectional study investigated uncontrolled hypertension, treatment, and predictors among hypertensive out-patients attending primary health care facilities in Johannesburg, South Africa. The WHO STEPwise approach to the surveillance of non-communicable diseases was used to collect data, including sociodemographic and lifestyle factors, health status, and measurements for anthropometry and blood pressure along with self-reported adherence to treatment, estimated through the general medication adherence scale. Uncontrolled hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg in diagnosed patients receiving anti-hypertensive treatment. Overweight and obesity were defined as a body mass index ≥25 and ≥30 kg/m2, respectively. Logistic regression models were used to assess the predictors of uncontrolled hypertension. Four hundred (n = 400) hypertensive out-patients (mean age: 50 ± 8 years) participated in this study, with most living in poor sociodemographic environments. The prevalence rate of uncontrolled hypertension was 57%. Obesity (62% vs. 42%, p ≤ 0.0001), salt consumption (90% vs. 55%, p ≤ 0.0001), alcohol intake (42% vs. 19%, p ≤ 0.0001), a smoking habit (23% vs. 4%, p ≤ 0.0001), alternative medicine use (51% vs. 40%, p = 0.043), and comorbidities (64% vs. 36%, p ≤ 0.0001) were higher in the uncontrolled group than the controlled group, whereas the prevalence of physical activity (38% vs. 15%, p ≤ 0.0001) was high in the controlled group vs. the uncontrolled. Overall, 85% of the patients moderately adhered to treatment, only 2% exhibited high adherence, and 13% demonstrated low adherence; over half of the patients received tri-therapy treatment. The predictors of uncontrolled hypertension are a number of prescribed antihypertensive therapies [adjusted odds ration = 2.39; 95% confidence interval: 1.48-3.87], treatment adherence [0.46; 0.21-0.97], salt consumption [28.35; 7.87-102.04], physical activity [0.22; 0.13-0.37], current alcohol use [2.10; 1.22-3.61], and current cigarette smoking [4.79; 1.88-12.18]. The high prevalence of uncontrolled hypertension in this study suggests a need to optimize prescriptions, adherence to BP-lowering medications, and lifestyle modifications. The management of comorbidities such as diabetes could offer considerable benefits in controlling blood pressure.

The postulated innocuity of lifetime exposure to aluminium should be reappraised.

Because of its chemical versatility and abundance in nature, aluminium is employed in a myriad of frequently used products - including cosmetics and food additives - and applications - drinking water purification procedures being an example. Despite what its widespread use might suggest, aluminium's harmlessness is a matter of debate in the scientific community. In this article we trace the lines of a growing questioning about the potential mutagenic effects of this metal, due to the data produced over the recent years, and with an eye to the discussions currently underway in this regard between the scientific community, industry, and regulatory bodies.

Pancreatic ß-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress.

Insulin resistance and pancreatic ß-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes (T2D). Beyond the detrimental effects of insulin resistance, inflammation and oxidative stress have emerged as critical features of T2D that define ß-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1ß are consistently associated with ß-cell failure in preclinical models and in people with T2D. Similarly, important markers of oxidative stress, such as increased reactive oxygen species and depleted intracellular antioxidants, are consistent with pancreatic ß-cell damage in conditions of T2D. Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D. The current review explores preclinical and clinical research on the patho-logical implications of inflammation and oxidative stress during the development of ß-cell dysfunction in T2D. Moreover, important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress during ß-cell failure in T2D. Underpinning the clinical relevance of the review, a systematic analysis of evidence from randomized controlled trials is covered, on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improve ß-cell function.

Precision Oncology by Point-of-Care Therapeutic Drug Monitoring and Dosage Adjustment of Conventional Cytotoxic Chemotherapies: A Perspective.

Therapeutic drug monitoring (TDM) of conventional cytotoxic chemotherapies is strongly supported yet poorly implemented in daily practice in hospitals. Analytical methods for the quantification of cytotoxic drugs are instead widely presented in the scientific literature, while the use of these therapeutics is expected to keep going for longer. There are two main issues hindering the implementation of TDM: turnaround time, which is incompatible with the dosage profiles of these drugs, and exposure surrogate marker, namely total area under the curve (AUC). Therefore, this perspective article aims to define the adjustment needed from current to efficient TDM practice for cytotoxics, namely point-of-care (POC) TDM. For real-time dose adjustment, which is required for chemotherapies, such POC TDM is only achievable with analytical methods that match the sensitivity and selectivity of current methods, such as chromatography, as well as model-informed precision dosing platforms to assist the oncologist with dose fine-tuning based on quantification results and targeted intervals.

Prevalence and influences of diabetes and prediabetes among adults living with HIV in Africa: a systematic review and meta-analysis.

INTRODUCTION: In people living with human immunodeficiency virus (PLHIV), traditional cardiovascular risk factors, exposure to HIV per se and antiretroviral therapy (ART) are assumed to contribute to cardiometabolic diseases. Nevertheless, controversy exists on the relationship of HIV and ART with diabetes. To clarify the relationship between HIV and type 2 diabetes, this review determined, in PLHIV in Africa, diabetes and prediabetes prevalence, and the extent to which their relationship was modified by socio-demographic characteristics, body mass index (BMI), diagnostic definitions used for diabetes and prediabetes, and HIV-related characteristics, including CD4 count, and use and duration of ART. METHODS: For this systematic review and meta-analysis (PROSPERO registration CRD42021231547), a comprehensive search of major databases (PubMed-MEDLINE, Scopus, Web of Science, Google Scholar and WHO Global Health Library) was conducted. Original research articles published between 2000 and 2021 in English and French were included, irrespective of study design, data collection techniques and diagnostic definitions used. Observational studies comprising at least 30 PLHIV and reporting on diabetes and/or prediabetes prevalence in Africa were included. Study-specific estimates were pooled using random effects models to generate the overall prevalence for each diagnostic definition. Data analyses used R statistical software and "meta" package. RESULTS: Of the 2614 records initially screened, 366 full-text articles were assessed for eligibility and 61 were selected. In the systematic review, all studies were cross-sectional by design and clinic-based, except for five population-based studies. Across studies included in the meta-analysis, the proportion of men was 16-84%. Mean/median age was 30-62 years. Among 86,412 and 7976 participants, diabetes and prediabetes prevalence rates were 5.1% (95% CI: 4.3-5.9) and 15.1% (9.7-21.5). Self-reported diabetes (3.5%) was lower than when combined with biochemical assessments (6.2%; 7.2%). DISCUSSION: While not statistically significant, diabetes and prediabetes were higher with greater BMI, in older participants, urban residents and more recent publications. Diabetes and prediabetes were not significantly different by HIV-related factors, including CD4 count and ART. CONCLUSIONS: Although HIV-related factors did not modify prevalence, the diabetes burden in African PLHIV was considerable with suboptimal detection, and likely influenced by traditional risk factors. Furthermore, high prediabetes prevalence foreshadows substantial increases in future diabetes in African PLHIV.

Therapeutic Drug Monitoring of Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis: Where Are We Now?

Drugs modulating the cystic fibrosis transmembrane conductance regulator (CFTR) protein, namely ivacaftor, lumacaftor, tezacaftor, and elexacaftor, are currently revolutionizing the management of patients with cystic fibrosis (CF), particularly those with at least one F508del variant (up to 85% of patients). These "caftor" drugs are mainly metabolized by cytochromes P450 3A, whose enzymatic activity is influenced by environmental factors, and are sensitive to inhibition and induction. Hence, CFTR modulators are characterized by an important interindividual pharmacokinetic variability and are also prone to drug-drug interactions. However, these CFTR modulators are given at standardized dosages, while they meet all criteria for a formal therapeutic drug monitoring (TDM) program that should be considered in cases of clinical toxicity, less-than-expected clinical response, drug or food interactions, distinct patient subgroups (i.e., pediatrics), and for monitoring short-term adherence. While the information on CFTR drug exposure-clinical response relationships is still limited, we review the current evidence of the potential interest in the TDM of caftor drugs in real-life settings.

Using a Syndemics Framework to Understand How Substance Use Contributes to Morbidity and Mortality among People Living with HIV in Africa: A Call to Action.

Substance use is increasing throughout Africa, with the prevalence of alcohol, tobacco, cannabis, and other substance use varying regionally. Concurrently, sub-Saharan Africa bears the world's largest HIV burden, with 71% of people living with HIV (PWH) living in Africa. Problematic alcohol, tobacco, and other substance use among PWH is associated with multiple vulnerabilities comprising complex behavioral, physiological, and psychological pathways that include high-risk behaviors (e.g., sexual risk-taking), HIV disease progression, and mental health problems, all of which contribute to nonadherence to antiretroviral therapy. Physiologically, severe substance use disorders are associated with increased levels of biological markers of inflammation; these, in turn, are linked to increased mortality among PWH. The biological mechanisms that underlie the increased risk of substance use among PWH remain unclear. Moreover, the biobehavioral mechanisms by which substance use contributes to adverse health outcomes are understudied in low- and middle-income countries (LMIC). Syndemic approaches to understanding the co-occurrence of substance use and HIV have largely been limited to high-income countries. We propose a syndemic coupling conceptual model to disentangle substance use from vulnerabilities to elucidate underlying disease risk for PWH. This interventionist perspective enables assessment of biobehavioral mechanisms and identifies malleable targets of intervention.

Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number.

Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum-in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues-incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.

Prevalence and determinants of chronic kidney disease in urban adults' populations of northern Cameroon.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem with growing prevalence in sub-Saharan Africa. AIM: Assess the prevalence and determinants of CKD in Garoua and Figuil cities of the North region of Cameroon. METHODS: A cross-sectional survey was conducted from January to June 2018 in the two cities, using a multi-level cluster sampling. All adults with low estimated glomerular filtration rate (eGFR) (< 60 ml/min/1.73 m2) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and/or albuminuria (≥ 30 mg/g) were reviewed three months later. Logistic regression models (accounting for the sampling strategy) were used to investigate the predictors of the outcomes. RESULTS: A total of 433 participants were included, with a mean age (95%CI) of 45.0 (43.4-46.6) years, 212 (48.7%) men, 294 (67.9%) from Garoua and 218 (45.6%) with no formal education. Risk factors for chronic nephropathy were highly prevalent including longstanding use of street medications (52.8%), herbal medicines (50.2%) and non-steroidal anti-inflammatory drugs (50%), alcohol consumption (34.4%), hypertension (33.9%), overweight/obesity (33.6%), hyperuricemia (16.8%), smoking (11.3%) and hyperglycemia (6.5%). The prevalence of CKD was 11.7% overall, 10.7% in Garoua and 13% in Figuil participants. Equivalents figures for CKD G3-5 and albuminuria were 2.8%, 2.0% and 4.5%; and 9.1%, 9.3% and 8.5%, respectively. History of diabetes, increase systolic blood pressure, hyperglycemia and hyperuricemia were predictors of CKD. CONCLUSION: The prevalence of CKD is as high in these northern cities as previously reported in southern cities of Cameroon, driven mostly by known modifiable risk factors of chronic nephropathy.

A Systematic Review of Complications Associated With Percutaneous Native Kidney Biopsies in Adults in Low- and Middle-Income Countries.

INTRODUCTION: Kidney biopsy is an important tool for making diagnoses and for assessing the drug treatment requirements and disease prognosis in the management of kidney diseases. There are variations in the rate of complications associated with kidney biopsies across countries, and this depends on various clinical and technical factors. The aim of this study is to report on complications associated with kidney biopsy performed in low- and middle-income countries. METHODS: Two reviewers searched studies in MEDLINE, Embase, Cochrane Reviews, and African Journals Online. A random effects meta-analysis method was used to pool estimates of complications. RESULTS: We identified 39 studies reporting on 19,500 kidney biopsies with overall complications (major + minor) rate of 14.9% (95% confidence interval = 11.4%-18.7%). Fewer complications were reported in biopsies performed with real-time ultrasound scans compared to those pre-marked using ultrasound or blind procedures (12.4% vs. 14.9% vs. 24.5%; P = 0.037), respectively. Complications, albeit lower for procedures performed with automated needles (13.3%), were not significantly different from those performed with nonautomated needles (17.3%; P = 0.588). Major complications included macroscopic hematuria (1.48%), nephrectomy (0.04%), blood loss requiring red cell transfusion (0.24%), angiographic intervention (0.22%), and death (0.01%). CONCLUSION: Complications associated with kidney biopsy in low- and middle-income countries are low, are comparable to those in other settings, and occur more sparingly when real-time ultrasound techniques or automated kidney biopsy needles are used. This suggests the need to expand the use of this procedure to improve diagnosis of kidney pathologies and choice of therapy when indicated.

The case for early identification and intervention of chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Chronic kidney disease (CKD) causes substantial global morbidity and increases cardiovascular and all-cause mortality. Unlike other chronic diseases with established strategies for screening, there has been no consensus on whether health systems and governments should prioritize early identification and intervention for CKD. Guidelines on evaluating and managing early CKD are available but have not been universally adopted in the absence of incentives or quality measures for prioritizing CKD care. The burden of CKD falls disproportionately upon persons with lower socioeconomic status, who have a higher prevalence of CKD, limited access to treatment, and poorer outcomes. Therefore, identifying and treating CKD at the earliest stages is an equity imperative. In 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a controversies conference entitled "Early Identification and Intervention in CKD." Participants identified strategies for screening, risk stratification, and treatment for early CKD and the key health system and economic factors for implementing these processes. A consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately for high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.

Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance!

Introduction: Broad-spectrum beta-lactams are commonly prescribed for empirical or selective treatment of bacterial infections in children with malignancies. In the immunocompromised, appropriate concentration exposure is crucial to ensure antimicrobial efficacy. Augmented renal clearance (ARC) is increasingly recognized in this population, and raises concern for unmet concentration targets. We conducted a retrospective evaluation of meropenem and piperacillin exposure in our hospital's pediatric hematology-oncology patients. Materials and Methods: We compared trough levels of meropenem and piperacillin in a cohort of unselected pediatric hematology-oncology patients stratified based on their estimated renal function as decreased, normal or with ARC, and on their neutrophil count. Results: Thirty-two children provided a total of 51 meropenem and 76 piperacillin samples. On standard intermittent intravenous regimen, 67% of all trough plasma concentrations were below targeted concentrations. In neutropenic children with bacterial infection, all meropenem and 60% of piperacillin levels were below target. Nearly two-thirds of total samples came from children with ARC. In these patients, antimicrobial exposure was insufficient in 85% of cases (compared to 36% in the decreased or normal renal function groups), despite a dosage sometimes exceeding the maximum recommended daily dose. Under continuous infusion of piperacillin, only 8% of plasma levels were insufficient. Discussion: Intermittent administration of meropenem and piperacillin often fails to ensure sufficient concentration exposure in children treated for malignancies, even at maximal recommended daily dosage. This can in part be attributed to ARC. We recommend thorough assessment of renal function, resolute dosage adjustment, continuous infusion whenever possible and systematic therapeutic drug monitoring.

Rising prevalence, and improved but suboptimal management, of hypertension in South Africa: A comparison of two national surveys.

Aim: To examine the changes in prevalence, awareness, treatment and control of hypertension between 1998 and 2016 in ≥15-year-old South African men and women and the sociodemographic characteristics associated with those changes. Methods: In nationally representative surveys in 1998 and 2016, multi-stage sampling was used to select, interview and collect blood pressure and anthropometric measurements in ≥15-year-old adults. Logistic regression analyses evaluated the independent effects of selected sociodemographic characteristics on hypertension management. Results: Among 13,217 participants in 1998 and 7830 in 2016 (59-60% women in both surveys), hypertension prevalence increased from 27% to 45% in men and 31% to 48% in women. Hypertension increased equally in participants with and without obesity and in daily cigarette smokers vs. their counterparts. Prevalence of awareness among participants with hypertension increased from 7% to 18% (men) and from 17% to 29% (women). Among those aware, hypertension treatment improved markedly from 8% to 85% (men) and from 12% to 82% (women). Hypertension control among those on treatment increased from 17% to 26% (men) and from 21% to 30% (women). Increasing age and survey year were consistently associated with higher prevalence, awareness, treatment and control of hypertension. The richest vs. poorer women, and lower vs. higher educated women were more likely to be treated for hypertension. Conclusions: The high and rising hypertension burden together with suboptimal awareness and control levels warrant greater attention to curb hypertension-related morbidity and mortality in South Africans. Novel strategies involving community-based or workplace hypertension programmes may overcome some barriers to optimal care.

Genomic Instability Is an Early Event in Aluminium-Induced Tumorigenesis.

Genomic instability is generally considered as a hallmark of tumorigenesis and a prerequisite condition for malignant transformation. Aluminium salts are suspected environmental carcinogens that transform mammary epithelial cells in vitro through unknown mechanisms. We report here that long-term culture in the presence of aluminium chloride (AlCl3) enables HC11 normal mouse mammary epithelial cells to form tumours and metastases when injected into the syngeneic and immunocompetent BALB/cByJ strain. We demonstrate that AlCl3 rapidly increases chromosomal structural abnormalities in mammary epithelial cells, while we failed to detect direct modulation of specific mRNA pathways. Our observations provide evidence that clastogenic activity-a well-recognized inducer of genomic instability-might account in part for the transforming abilities of aluminium in mammary epithelial cells.

Protocol for systematic review and meta-analysis: impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases.

INTRODUCTION: Statins, also known as 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, are lipid-lowering agents that are central in preventing or reducing the complications of atherosclerotic cardiovascular disease. Because statins have anti-inflammatory properties, there is considerable interest in their therapeutic potential in other chronic inflammatory conditions. We aim to identify the statin with the greatest ability to reduce systemic inflammation, independent of the underlying disease entity. METHODS AND ANALYSIS: We aim to conduct a comprehensive search of published and peer-reviewed randomised controlled clinical trials, with at least one intervention arm of a Food & Drug Administration-licensed or European Medicines Agency-licensed statin and a minimum treatment duration of 12 weeks. Our objective is to investigate the effect of statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin) on lipid profile, particularly, cholesterol low-density lipoprotein and inflammation markers such as high-sensitive C reactive protein (hsCRP), CRP, tumour necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8, soluble cluster of differentiation 14 (sCD14) or sCD16 in adults, published in the last 20 years (between January 1999 and December 2019). We aim to identify the most potent statin to reduce systemic inflammation and optimal dosing. The following databases will be searched: Medline, Scopus, Web of Science and Cochrane Library of Systematic Reviews. The risk of bias of included studies will be assessed by Cochrane Risk of Bias Tool and Quality Assessment Tool for Quantitative Studies. The quality of studies will be assessed, to show uncertainty, by the Jadad Score. If sufficient evidence is identified, a meta-analysis will be conducted with risk ratios or ORs with 95% CIs in addition to mean differences. ETHICS AND DISSEMINATION: Ethics approval is not required as no primary data will be collected. Results will be presented at conferences and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020169919.