Physician-brief advice for promoting smoking cessation among cancer patients on treatment in low and middle-income countries: a scoping review.

INTRODUCTION: Physician-brief advice has been utilized in high-income countries to promote smoking cessation among cancer patients. Empirical evidence on its effectiveness among cancer patients in low and middle-income countries (LMICs) is lacking. The gap could be due to inadequate training, and competing healthcare priorities, leading to insufficient implementation of targeted smoking cessation interventions in oncology settings. We undertook this scoping review to determine if physician-brief advice is effective in promoting smoking cessation among cancer patients in LMICs. METHODS: We conducted a literature search of all relevant articles across five databases: Cochrane Central Register of Controlled Trials, Cochrane Library (Tobacco Addiction Group trials), World Conference on Lung Cancer proceedings, PubMed, and Google Scholar up to November 2023, using pre-defined inclusion criteria and keywords. The study population was cancer survivors in LMICs, the intervention was smoking cessation advice by a physician in a clinic or oncology center during a consultation, and the outcome was the effect of smoking cessation programs in discontinuing smoking among cancer survivors in LMICs. RESULTS: Overall, out of every 10 cancer patients in LMICs, about seven were smokers, and one-half had received physician-brief advice for smoking cessation. Physician-brief advice was more likely to be delivered to patients with smoking-related cancer (Cohen's d = 0.396). This means that there is a noticeable difference between patients with smoking-related cancer compared to those with cancer unrelated to smoking. Smoking cessation failure was due to the inability to cope with the symptoms of withdrawal, missed smoking cessation clinic visits, mental health disorders, limited time and resources, and minimal patient-physician contact. CONCLUSION: There is very little literature on the frequency of use or the efficacy of physician-brief advice on smoking cessation in LMICs. The literature suggests that cancer patients in LMICs have low self-efficacy to quit smoking, and smoking cessation is rarely part of cancer care in LMICs. Physicians in LMICs should be trained to use motivational messages and good counseling techniques to improve smoking cessation among cancer patients. Policymakers should allocate the resources to implement physician-brief advice and design training programs for physicians focusing on physician-brief advice tailored to cancer patients.

Overall and central obesity and prostate cancer risk in African men.

PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multi-center, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI ≥ 30 kg/m2), 26% and 90% had WC > 97 cm and WHR > 0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive PCa, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR = 1.38, 95% CI 0.99-1.93), and central obesity (WC > 97 cm: OR = 1.60, 95% CI 1.10-2.33; and WHtR > 0.59: OR = 1.68, 95% CI 1.24-2.29) were positively associated with D'Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

Epidemiology of physical inactivity in Nigeria: a systematic review and meta-analysis.

BACKGROUND: Physical activity is crucial to preventing noncommunicable diseases. This study aimed to provide up-to-date evidence on the epidemiology of insufficient physical activity across Nigeria to increase awareness and prompt relevant policy and public health response. METHODS: A systematic literature search of community-based studies on physical inactivity was conducted. We constructed a meta-regression epidemiologic model to determine the age-adjusted prevalence and number of physically inactive persons in Nigeria for 1995 and 2020. RESULTS: Fifteen studies covering a population of 13 814 adults met our selection criteria. The pooled crude prevalence of physically inactive persons in Nigeria was 52.0% (95% CI: 33.7-70.4), with prevalence in women higher at 55.8% (95% CI: 29.4-82.3) compared to men at 49.3% (95% CI: 24.7-73.9). Across settings, prevalence of physically inactive persons was significantly higher among urban dwellers (56.8%, 35.3-78.4) compared to rural dwellers (18.9%, 11.9-49.8). Among persons aged 20-79 years, the total number of physically inactive persons increased from 14.4 million to 48.6 million between 1995 and 2020, equivalent to a 240% increase over the 25-year period. CONCLUSIONS: A comprehensive and robust strategy that addresses occupational policies, town planning, awareness and information, and sociocultural and contextual issues is crucial to improving physical activity levels in Nigeria.

Good Financial Grant Practice: A Tool for Developing and Demonstrating Institutional Financial and Grant Management Capacity in Global Health.

The administration and governance of grant funding across global health organizations presents enormous challenges. Meeting these challenges is crucial to ensuring that funds are used in the most effective way to improve health outcomes, in line with the United Nations' Sustainable Development Goal 3, "Ensure healthy lives and promote well-being for all at all ages." The Good Financial Grant Practice (GFGP) Standard (ARS 1651) is the world's first and, currently, only international standard for the financial governance and management of grant funding. Through consensus building and global harmonization between both low- and middle-income and high-income country players, the GFGP Standard has achieved a leveling impact: GFGP applies equally to, and can be implemented by, all types of organization, regardless of location, size, or whether they predominantly give or receive funding. GFGP can be used as a tool for addressing some of the challenges of the current funding model. Here, we describe our experiences and lessons learned from implementing GFGP across 4 diverse research institutions in India, Nigeria, Colombia, and the Philippines as part of our National Institute for Health Research Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance.

Medication adherence and 24-h blood pressure in apparently uncontrolled hypertensive Nigerian patients.

BACKGROUND: Uncontrolled hypertension is a major risk for major cardiovascular events. While medication adherence determines blood pressure (BP) control, studies on treatment adherence among apparently uncontrolled hypertensives are sorely lacking in sub-Saharan Africa. We report the pattern and correlate of medication adherence among the uncontrolled hypertensive population. MATERIALS AND METHODS: We investigated 148 age- and sex-matched hypertensive adults on anti-hypertensive medication for a minimum of 1 year. Apparent uncontrolled BP was defined as clinic BP ≥140/90 mmHg, whereas 24-h ambulatory BP monitoring was used to determine the true uncontrolled hypertension and other BP phenotypes. Using the 8-item Morisky medication adherence scale participants were classified into high, moderate and low adherence while Modified Morisky Scale was used to assess knowledge and motivation. RESULTS: The mean age and BP were 61 ± 13.3 years and 158/91 mmHg, respectively. High adherence was found in 4.1% of the participants while 68.9% and 27% had moderate and low adherence, respectively. A third had true uncontrolled hypertension. A high proportion of the study participants also had a high motivation (68.9%) and knowledge (89.2%). Medication adherence was associated with motivation (P = 0.0001), knowledge (P = 0.002) and obesity (P = 0.036). Knowledge was an independent determinant of medication adherence with no significant effect on BP control. CONCLUSION: High medication adherence was low and a third had true uncontrolled hypertension. Knowledge was an independent predictor of medication adherence with no significant effect on blood control. High medication adherence rather than moderate adherence, and knowledge are indeed needed for adequate BP control.

A Qualitative Analysis of Selected Stakeholders' Viewpoints on Tobacco Control in Nigeria.

Nigeria is a signatory to the Framework Convention on Tobacco Control. However, tobacco control efforts have been fraught with challenges. These challenges cannot be presumed to be independent of tobacco industry manipulation. We examined submissions and viewpoints from prominent tobacco control stakeholders across social, administrative, and political strata to identify convergence with tobacco industry viewpoints. We illustrate how these convergences pose a threat to effective tobacco control in Nigeria. A thematic analysis of stakeholder viewpoints was conducted on submissions to the national assembly during the Tobacco Control Bill public hearings and various industry documents. Areas of convergence with tobacco industry narratives were then explored. Significant convergence in views was observed between government agencies, social groups, and the tobacco industry. These were for narratives on constitution of a National Tobacco Control Committee, use of automated vending machines, designation of smoking areas, report to regulatory agencies, and negative effect of tobacco control on trade and poverty. There was evidence of tobacco industry interference in tobacco control efforts, which manifested in some prominent tobacco control stakeholders adopting the narratives of the tobacco industry. We advocate a constant watchfulness over the activities of these stakeholders and a proactive engagement with evidence-based antitobacco dialogue.

Improving outcomes in cancer diagnosis, prevention and control: barriers, facilitators and the need for health literacy in Ibadan Nigeria.

BACKGROUND: Cancers constitute a significant public health problem in Nigeria. Breast, cervix and prostate cancers are leading causes of cancer-related deaths. Changing diets, lifestyles, HIV/AIDS and macro-structural factors contribute to cancer morbidity and mortality. Poor health information linking cancer risk to individual behaviors, environmental pollutants and structural barriers undermine prevention/control efforts. Studies suggest increasing health literacy and empowering individuals to take preventive action will improve outcomes and mitigate impact on a weak health system. METHODS: We obtained qualitative data from 80 men, women, and young adults in 11 focus groups to assess beliefs, risk-perceptions, preventive behaviors and perceptions of barriers and facilitators to cancer control in Ibadan, Nigeria and conducted thematic analysis. RESULTS: Participants demonstrated awareness of cancers and mentioned several risk factors related to individual behaviors and the environment. Nonetheless, myths and misconceptions as well as micro, meso and macro level barriers impede prevention and control efforts. CONCLUSION: Developing and implementing comprehensive context-relevant health literacy interventions in community settings are urgently needed.Copyright © 2016 John Wiley & Sons, Ltd.

Assessment of tobacco control efforts in three Sub-Saharan African countries.

BACKGROUND: Tobacco industry's undermining of tobacco control goes on unabated in sub-Saharan African countries, especially in Kenya, Nigeria, and Uganda. The Framework Convention on Tobacco Control (FCTC) contains provisions aimed at curbing these activities. However, the level to which FCTC is implemented and the strength of each country's tobacco control law will determine its usefulness in this regard. We determined the implementation status and strength of tobacco control laws in Kenya, Nigeria, and Uganda. MATERIALS AND METHODS: The World Health Organization and Campaign for Tobacco-Free Kids websites were queried for secondary data related to tobacco control. Sources and data were disambiguated and reported as tables. Composite scores for implementation were computed based on the number of indicators of the articles of the FCTC reported on by each country. Strength of tobacco control law (SoTCL) was computed based on the total number of domains of the laws meeting a defined acceptable standard. Total obtainable score for implementation and SoTCL were 148 and 38, respectively. RESULTS: On the FCTC, Kenya, Nigeria, and Uganda achieved 75, 61.5, and 46.6% implementation, respectively. SoTCL was weakest in the smoke-free domain for Kenya, tobacco advertisement promotion and sponsorship domain for Nigeria, and packaging and labeling domain for Uganda. SoTCL scores were 18 (47.4%), 20 (52.6%), and 34 (89.5%) for Nigeria, Kenya, and Uganda, respectively. CONCLUSION: Kenya, Nigeria, and Uganda will need to strengthen their tobacco control laws through appropriate amendment as well as regulatory mechanisms that guarantee alignment with FCTC and the implementation thereof.

Assessment of Emergency Obstetric Care Services in Ibadan-Ibarapa Health Zone, Oyo State, Nigeria.

Nigeria's high maternal mortality has been attributed to poor utilization of obstetric care services to handle complications of pregnancy and childbirth. But how available are standard emergency obstetric care services? This facility based cross sectional study assessed the availability and accessibility of emergency obstetric care services in Oyo State, Nigeria. Using a multi-stage sampling technique, 61 primary and 10 secondary health care facilities were selected. Data was collected using a structured questionnaire from the heads of the maternity units. Spatial mapping of the facilities was also produced. Results showed availability of comprehensive emergency obstetric care (CEmOC) facilities (0-3.9/500,000 population) was adequate, however a gross lack of basic emergency obstetric care (BEmOC) facilities (0-5.4/500,000 population) was observed, where available, they were clustered in the urban settlements. Prompt action needs to be taken to upgrade basic emergency obstetric care facilities accessible to the larger rural population dwellers to improve maternal health indices.

Enacted and implied stigma for dementia in a community in south-west Nigeria.

BACKGROUND: Dementia is a chronic progressive disease that mostly affects the elderly. There is often a stigma surrounding dementia patients because of poor awareness about the disease. In Nigeria, this stigma and related attitudes have not been fully explored. In this study, we assessed the attitude of people towards demented individuals in a transitional community in Nigeria. METHODS: The study used a mixed methods approach. Focused group discussions exploring the concept of dementia were conducted among six community groups, and quantitative data was obtained from an interviewer-administered questionnaire. A total of 313 respondents were selected with a cluster sampling technique. RESULTS: Only 212 respondents (67.7%) were aware of dementia. 'Memory loss disease', 'ageing disease', 'disease of insanity', 'brain disorder', 'disease of forgetfulness', and 'dull brain' are the common names used to describe dementia in the community. Enacted stigma was evident as 36% of respondents felt dementia was associated with shame and embarrassment in the community. Implied stigma was evident in another third that opined that demented individuals would prefer not to know or let others know that they have the disease. Also, 28% were of the opinion that people do not take those with dementia seriously. Of the 22 (10.4%) that reported having received structured information about dementia, 16 (72.7%) got the information from health facilities. Qualitative data revealed the presence of enacted stigma in the community as some referred to affected individuals by derogatory names such as 'madman'. Some statements from the focus group discussion participants also gave useful insights into the scorn with which demented individuals are sometimes treated. CONCLUSION: The presence of enacted and implied stigma related to dementia within the community calls for concern. More research efforts are needed to unravel the burden of stigma within communities and best practice for stigma-reducing interventions.

Association of depression and anxiety with uncontrolled hypertension: A cross-sectional study in Southwest Nigeria.

Background: Hypertension is a medical condition of public health concern that increases the risk of chronic noncommunicable diseases and mortalities. In recent years, understanding its coexistence with other comorbidities has been the focus of better management. However, the relationship between hypertension and depression or anxiety has been contentious issue, with diverse findings reported by different studies. Understanding this relationship will be crucial for blood pressure control and reducing the mortality associated with hypertension. Therefore, this study was conducted to determine the association between depression or anxiety and hypertension control. Methods: A cross-sectional study was conducted among 321 hypertensive patients accessing care in two hospitals. Depression and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). The relationship between blood pressure control and depression or anxiety was assessed using binary logistic regression. Results: The prevalence of depression and anxiety was 12.1% and 23.1%, respectively. Up to 261 (81.3%) participants had uncontrolled blood pressure. Of these 261 participants, 14.2% and 23.4% had depression and anxiety, respectively. Depression was associated with an increased risk of uncontrolled blood pressure after adjusting for sex, smoking cigarettes, age, marital status, and exercise (odds ratio (OR) = 7.751, 95% confidence interval (CI) = 1.79-43.4, P = 0.011). Conclusion: Depression appears to be independently associated with an increased risk of uncontrolled blood pressure. It is therefore relevant for healthcare providers to assess for depression in patients with hypertension to ensure better hypertensive control.

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men.

Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10-5, r2 < 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.

Factors associated with sexual abstinence among out-of-school females in a transitional town in Oyo State, South-Western Nigeria.

One hundred and forty-three respondents participated in this cross-sectional study and 42 (29.4%) of them had never had sex. About 92% engaged in at least one leisure activity. Factors significantly associated with abstinence follow: living arrangement, type of occupation, mode of earning, self-esteem, alcohol use, and some leisure activities (p < .05). Factors predictive of abstinence were living with parents or other relatives, earning weekly and monthly wages as opposed to daily wages, high self-esteem, and reading of novels during leisure time. Intensified efforts are necessary to enhance the identified protective factors in order to promote abstinence among out-of-school females.

Cigarette health warning label compliance in Nigeria: A multi-city observational study.

INTRODUCTION: Tobacco remains the world's leading preventable cause of death, with the majority of tobacco-caused deaths occurring in low- and middle-income countries. The first global health treaty, the Framework Convention on Tobacco Control (FCTC), outlines a set of policy initiatives that have been demonstrated as effective in reducing tobacco use. Article 11 of the FCTC focuses on using the tobacco package to communicate tobacco-caused harms; it also seeks to restrict the delivery of misleading information on the pack about the product.The objective of his study is to establish a surveillance system for tobacco packs in Nigeria to assess pack compliance with in-country health warning label requirements. The Tobacco Pack Surveillance System (TPackSS) monitors whether required health warnings on tobacco packages are being implemented as intended and identifies pack designs that might violate the communication of harm-related information and undermine the impact of the country's tobacco packaging laws. METHODS: Tobacco cigarette packs were collected in three cities in 2019-2020. The intention was, to the extent possible, to construct a census of 'unique' pack presentations available for purchase in Nigeria. We implemented the TPackSS standardized Protocol for acquiring packs from 36 diverse neighborhoods across three cities. At the time of purchase, data on the price and place of acquisition of each pack were recorded. We photographed packs, coded, and archived them. Each pack was coded for compliance according to the current health warning label laws. Each pack was coded by two independent coders consistently. We routinely measured intercoder reliability and only retained variables for which a good level of reliability was achieved. RESULTS: Across the three cities in Nigeria, the team collected 90 tobacco packs. Overall, 77% of packs evaluated for HWL compliance complied with all the relevant common indicators of HWL compliance. There was a 92% compliance with the location of the HWL (e.g. top or bottom of pack, front or back panel) with in-country requirements. Of the four compliance indicators, the size of the HWL (the minimum required coverage) showed the lowest compliance (31%) (i.e. the HWL was too small on most of the packs). Label elements (such as color contrast or content of warnings) showed 85% compliance overall. CONCLUSIONS: The analysis of the packs showed various levels of compliance with Health Warning Label provisions for Nigeria. Periodic evaluations are required to ensure that minimum requirements are met.

Characteristics and outcomes of patients hospitalized with COVID-19 at a tertiary hospital in Nigeria.

Background: Data regarding the features and outcomes of hospitalized COVID-19 patients in Africa are increasingly available. Objectives: To describe socio-demographic, clinical and laboratory characteristics and outcomes of COVID-19 patients. Methods: A cross-sectional study of 86 adult patients hospitalized with COVID-19 between March and November 2020. Characteristics were described in survivors and non-survivors. Results: Mean age was 60.9±16.1 years, 53(61.6%) were male. Co-morbidities were found in 77(89.5%) patients. On severity, 6(7%) were mild, 23(26.7%) moderate, 51(59.3%) severe and 6(7%) critical. Oxygen saturation and respiratory rate were 71±22% and 38±11/minute in non-survivors and 90±7% and 31±7/minute in survivors respectively (p<0.001, p<0.001)). Overall mortality was 47.7% with no death among patients with mild disease and deaths in all patients with critical disease. Duration of hospitalization was 2.0(1.0-4.5) days in those who died and 12(7.0-15.0) days in those who survived (p<0.001). Of the 42 patients that received dexamethasone, 11(26.2%) died, while 31(73.8%) survived (p=<0.001). Conclusion: Most of the patients had co-morbidities and there was high mortality in patients with severe and critical COVID-19. Mean oxygen saturation was low and respiratory rate high overall. Factors associated with mortality included: Significantly greater hypoxia and tachypnea, less dexamethasone use and shorter hospitalization.

Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction.

We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.

Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Estimating the prevalence of COPD in an African country: evidence from southern Nigeria.

# Background: Though several environmental and demographic factors would suggest a high burden of chronic obstructive pulmonary disease (COPD) in most African countries, there is insufficient country-level synthesis to guide public health policy. # Methods: A systematic search of MEDLINE, EMBASE, Global Health and African Journals Online identified studies reporting the prevalence of COPD in Nigeria. We provided a detailed synthesis of study characteristics, and overall median and interquartile range (IQR) of COPD prevalence in Nigeria by case definitions (spirometry or non-spirometry). # Results: Of 187 potential studies, eight studies (6 spirometry and 2 non-spirometry) including 4,234 Nigerians met the criteria. From spirometry assessment, which is relatively internally consistent, the median prevalence of COPD in Nigeria was 9.2% (interquartile range, IQR: 7.6-10.0), compared to a lower prevalence (5.1%, IQR: 2.2-15.4) from studies based on British Medical Research Council (BMRC) criteria or doctor's diagnosis. The median prevalence of COPD was almost the same among rural (9.5%, IQR: 7.6-10.3) and urban dwellers (9.0%, IQR: 5.3-9.3) from spirometry studies. # Conclusions: A limited number of studies on COPD introduces imprecision in prevalence estimates and presents concerns on the level of response available across different parts of Nigeria, and indeed across many countries in sub-Saharan Africa.

A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19.

Background: The nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19. Methods: This is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286). Results: There was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492-1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2-28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341-2.636, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251-1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797-2,557), above its putative EC90 in 54% of patients. Tizoxanide was undetectable in saliva. Conclusion: Nitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04459286], identifier [NCT04459286].

Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.