Multinational, Multicenter Evaluation of Prostate Cancer Tissue in Sub-Saharan Africa: Challenges and Opportunities.

PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.

Analysis, treatment modality and demographic characteristics of urolithiasis patients visiting Korle-Bu Teaching Hospital in Ghana.

Background: Globally urolithiasis is on the rise and gradually becoming a public health concern due to the associated complications. This study reviewed the demographic characteristics, the chemical composition of stones, treatment modality and duration of hospitalisation of urolithiasis patients at Korle-Bu Teaching Hospital, Accra, Ghana. Materials and Methods: This was a retrospective study conducted between March 2019 and April 2022. Data from consecutive patients treated for urolithiasis were used for this study. Data on demographic characteristics, stones chemical composition, urine factors, urolithiasis treatment modality and duration of hospital stay after therapy were collated and analysed using descriptive and inferential approaches. Results: The age of the patients ranged from 2 to 75 years with a mean of 45 (±13.4). The predominant age group for stone formation was 30-39 years - 52(26.3%). Urolithiasis was common among patients in the formal employment sector: 81(40.9%). All stones had two or more chemical compositions, with the combination of calcium oxalate monohydrate, calcium oxalate dihydrate and uric acid being the predominant stone type: 88(57.5%). Ureteroscopy with semi-rigid and Percutaneous nephrolithotomy were the predominant treatment modalities: 105(53.0%) and 74(37.4%), respectively. Escherichia coli was responsible for most urinary tract infections in urolithiasis patients 8(4.0%) and the least duration of hospital stay after the procedure was associated with the use of semi-rigid ureteroscope as the treatment modality with a median duration of 2 days (1-2 days) with P < 0.0001. Conclusions: Urolithiasis was predominant among professionals in the formal sector. All stones were mixed with Calcium oxalate monohydrate, calcium oxalate dihydrate, and uric acid combination being the majority. Ureteroscopy with semi-rigid and percutaneous nephrolithotomy were the common treatment modality.

Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma.

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10-6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10-8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10-6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.

Compliance with cocoa quality management practices in Ghana; To what extent are cocoa farmers complying?

Despite the fact that adhering to cocoa quality management practices (QMPs) is crucial to satisfy consumer food safety standards and receive premium cocoa pricing, evidence of cocoa farmers' compliance with these recommended QMPs is scanty in Ghana. The purpose of this study was to assess the extent and antecedents of farmers' compliance with six QMPs including pest and disease, harvesting and pod storage, pod breaking and bean removal, fermentation, drying, and bagging and storage practices in Ghana. Data from 200 farmers was solicited and analyzed using a compliance index as well as a seemingly unrelated regression (SURE) model to account for cross-correlation effects among six recommended QMPs. The results show an overall index of 2.46, implying that the cocoa farmers moderately comply with the six QMPs. Specifically, compliance levels for fermentation (index = 2.90) and drying (index = 2.92) practices are high, while farmers showed low compliance with bagging and storage practices (index = 1.33). The SURE model exhibits heterogeneous covariates that influence farmers' compliance across the six QMPs. However, extension access, sex of the farmer, and to some extent awareness of quality management practices, as well as education, are significant determinants of compliance across all six quality management practices. These findings have implications for strengthening the Extension Services Division of COCOBOD and gender mainstreaming of cocoa quality improvement training to address the challenges of women cocoa farmers.

Autosomal dominant polycystic kidney disease with ectopic unilateral multicystic kidney: a case report.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder and the fourth cause of death of end-stage renal disease. The disease has a prevalence of 1:400-1:1000 accounting for 10% of patients on dialysis. In most ADPKD patients, bilateral kidneys are similarly affected, with numerous fluid-filled cysts arising from different nephron segments. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic. CASE PRESENTATION: We report a case of a 46-year-old Ghanaian male patient who presented with left flank pain and hematuria with high BP and deranged renal function. Abdominal ultrasonography showed both kidneys to be larger than normal and had multiple cysts of varying sizes with the right kidney located in the right iliac fossa. Follow up Abdominopelvic computer tomographic scan (CT-Scan) without contrast showed enlarged kidneys with the renal parenchyma replaced by innumerable cyst of varying sizes. The right kidney was ectopically located in the right aspect of the pelvis. A diagnosis of ADPKD with right pelvic ectopic multicystic kidney was made. He was put on antihypertensives, analgesia for the left flank pain and to have follow up at the urology and nephrology departments. CONCLUSION: In most ADPKD patients, bilateral kidneys are similarly affected. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic.

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.

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.

Multiple bladder calculi after radical prostatectomy due to bladder neck stenosis in a patient with hypertrophic scar: A case report.

INTRODUCTION AND IMPORTANCE: Bladder calculi after radical prostatectomy is rare and usually associated with migrated clips into the bladder forming a nidus. We present a patient with multiple bladder calculi resulting from bladder neck stenosis after radical prostatectomy causing bothersome lower urinary tract symptoms. He had an associated hypertrophic scar. CASE PRESENTATION: A 60-year-old man of African ancestry presented with recent onset of irritative urinary symptoms three years after radical prostatectomy. Abdomen pelvic ultrasound and pelvic X-ray revealed a urinary bladder calculus. Examination of the previous radical prostatectomy scar found him to have a hypertrophic scar. He had urethroscopy with bladder neck incision for bladder neck stenosis and cystolithotomy with resolution of the symptoms. CLINICAL DISCUSSION: The presentation was that of dysuria and frequency three years after radical prostatectomy. The cause of the symptoms was diagnosed after an abdomen pelvic ultrasound and pelvic X-ray as multiple bladder calculi. This is a rare finding with the few reported cases associated with clips that migrated to the urinary bladder forming a nidus for the calculi. This was of consideration in the case presented, however, the findings at urethroscopy revealed bladder neck stenosis suggesting stasis as possible cause of the bladder calculi. The symptoms resolved after bladder neck incision and cystolithotomy. CONCLUSION: In addition to clips forming a nidus for calculi in the urinary bladder after radical prostatectomy, bladder neck stenosis being the cause of urinary bladder calculi should be considered in a patient with hypertrophic scar.

Determinants of Mortality among Patients Managed for Prostate Cancer: Experience from Korle Bu Teaching Hospital in Ghana.

Background: Over the past two decades, diagnosis and treatment approaches for men with prostate cancer have changed dramatically, with improvements in established prostate cancer treatments and new treatment strategies. However, In sub-Saharan African countries, there is a paucity of data on the characteristics and treatment of men who eventually die from Prostate Cancer (PCa). We used the clinical records of patients who died from PCa to describe the natural history and treatment PCa patients in Ghana. Methods: From 2013 to 2022, the medical records of 234 men who died of PCa at a tertiary hospital in Ghana were prospectively collected and retrospectively analysed. Results: The mean age at death was 71.6 years, and the median was 72.5 years. 51.3% died within 24 months of diagnosis, 23.0% between 2 and 5 years after diagnosis, and a quarter survived for more than 5 years. Over 80% presented with advanced disease, characterised by high prostate-specific antigen (PSA) levels, a high T stage on DRE, and evidence of metastasis. 43.6% presented with haemoglobin levels below 10ng/dl at diagnosis. These patients had the worst outcome, with 73% dying less than 2 years after diagnosis. The 5-yr survival rate of patients who presented with metastatic disease was 21.2 %. Over 80% were treated with bilateral total orchidectomy, with less than 10% receiving treatment intensification with the newer generation antiandrogens or chemotherapy. Conclusion: Our analysis shows that patients who die from PCa have aggressive disease, are diagnosed at an advanced stage, and are relatively younger than in Western countries. There is also a slow uptake of newer treatment strategies for metastatic prostate cancer. These results confirm literature suggesting that blacks have poorer outcomes due to the disease's aggressive nature. Further research is needed to understand the mechanisms and also define appropriate management for metastatic PCa in sub-Saharan Africa.

Safe duration of silicon catheter replacement in urological patients.

Objectives: This study compared the infection rates, degree of encrustation, symptoms, and complications in patients regarding the duration of urethral catheterisation (three weeks, six weeks, and eight weeks). Design: A cross-sectional study with stratified simple random sampling. Setting: Urology Unit, Korle Bu Teaching Hospital. Participants: One hundred and thirty-seven male patients with long-term urinary catheters. Interventions: Participants were grouped into 3 weeks, 6 weeks, and 8 weeks duration of catheter replacements. Primary outcomes measures: Symptoms due to the urinary catheters, urinalysis, urine and catheter tip cultures, sensitivity, and catheter encrustations were assessed. Results: Eighty-six patients had a primary diagnosis of benign prostatic hyperplasia (BPH), 35 had urethral strictures,13 had prostate cancer, two had BPH and urethral strictures, and one participant had bladder cancer. There was no difference in the symptoms the participants in the different groups experienced due to the urinary catheters (p > 0.05). The frequency of occurrence of complications (pyuria, p = 0.784; blocked catheter, p=0.097; urethral bleeding, p=0.148; epididymo-orchitis, p=0.769 and bladder spasms, p=1.000) showed no differences in the three groups. There was no statistical difference in the urinalysis for the three groups (p>0.05) and the degree of encrustations (3 weeks: 0.03 ± 0.06, 6 weeks: 0.11±0.27 and eight weeks: 0.12 ±0.27) with p=0.065. Conclusions: In this study, the duration of urinary catheterisation using silicone Foley's catheters did not influence the complication and symptom rates; hence silicon catheters can be placed in situ for up to 8 weeks before replacement instead of the traditional three-weekly change. Funding: Enterprise Computing Limited.

Circulating trans fatty acids are associated with prostate cancer in Ghanaian and American men.

The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer. Blood levels of circulating fatty acids vary significantly between the three population groups, particularly trans, omega-3 and omega-6 fatty acids. FADS1/2 germline genetic variants and lifestyle factors explain some of the variation in fatty acid levels, with the FADS1/2 locus showing population-specific associations, suggesting differences in their control by germline genetic factors. All trans fatty acids, namely elaidic, palmitelaidic, and linoelaidic acids, associated with an increase in the odds of developing prostate cancer, independent of ancestry, geographic location, or potential confounders.

Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry.

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.

Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry.

Genome-wide polygenic risk scores (GW-PRS) have been reported to have better predictive ability than PRS based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer risk variants from multi-ancestry GWAS and fine-mapping studies (PRS 269 ). GW-PRS models were trained using a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls used to develop the multi-ancestry PRS 269 . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California/Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI=0.635-0.677) in African and 0.844 (95% CI=0.840-0.848) in European ancestry men and corresponding prostate cancer OR of 1.83 (95% CI=1.67-2.00) and 2.19 (95% CI=2.14-2.25), respectively, for each SD unit increase in the GW-PRS. However, compared to the GW-PRS, in African and European ancestry men, the PRS 269 had larger or similar AUCs (AUC=0.679, 95% CI=0.659-0.700 and AUC=0.845, 95% CI=0.841-0.849, respectively) and comparable prostate cancer OR (OR=2.05, 95% CI=1.87-2.26 and OR=2.21, 95% CI=2.16-2.26, respectively). Findings were similar in the validation data. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the multi-ancestry PRS 269 constructed with fine-mapping.

Linkage between working conditions and wellbeing: Insight from migrant and native farmhands on Ghana's cocoa farms.

Working conditions and wellbeing (quality of life) could be linked, and they in turn enhance social and economic development. Nevertheless, working conditions of farmhands have largely been ignored in policy and research. We explored working conditions of migrant and native farmhands on Ghana's cocoa farms, and implications on wellbeing, using primary data from 600 respondents. Multidimensional Poverty Index, Department for International Development sustainable livelihood approach, World Food Programme asset score, Zellner's seemingly unrelated regression and multinomial logistic regression were adopted. Living standards, resilience, health and asset ownership of farmhands were generally low. Natives had higher living standards than migrants. However, migrants had better food security, and were more resilient to shocks than natives. Working and living conditions like years as a farmhand, closeness to social amenities, years migrant had stayed in community, type of migrant, being joined by a household member, working hours and days, type of agreement, category of farmhand, bonuses, satisfaction with working conditions, and income influence living standards, resilience, health and asset ownership. Thus, there is a link between working conditions and wellbeing of cocoa farmhands. Farmhands should be given long-term contracts, bonuses/incentives and personal protective equipment (PPE) by cocoa farmers. Government and private agencies should provide social amenities/infrastructure in cocoa-growing communities. Farmhands should do their own farms and join associations.

Safe duration of silicon catheter replacement in urological patients

Objectives: This study compared the infection rates, degree of encrustation, symptoms, and complications in patients regarding the duration of urethral catheterisation (three weeks, six weeks, and eight weeks). Design: A cross-sectional study with stratified simple random sampling Setting: Urology Unit, Korle Bu Teaching Hospital Participants: One hundred and thirty-seven male patients with long-term urinary catheters Interventions: Participants were grouped into 3 weeks, 6 weeks, and 8 weeks duration of catheter replacementsPrimary outcomes measures: Symptoms due to the urinary catheters, urinalysis, urine and catheter tip cultures, sensitivity, and catheter encrustations were assessed. Results: Eighty-six patients had a primary diagnosis of benign prostatic hyperplasia (BPH), 35 had urethral strictures,13 had prostate cancer, two had BPH and urethral strictures, and one participant had bladder cancer. There was no difference in the symptoms the participants in the different groups experienced due to the urinary catheters (p > 0.05). The frequency of occurrence of complications (pyuria, p = 0.784; blocked catheter, p=0.097; urethral bleeding, p=0.148; epididymo-orchitis, p=0.769 and bladder spasms, p=1.000) showed no differences in the three groups. There was no statistical difference in the urinalysis for the three groups (p>0.05) and the degree of encrustations (3 weeks: 0.03 ± 0.06, 6 weeks: 0.11±0.27 and eight weeks: 0.12 ±0.27) with p=0.065. Conclusions: In this study, the duration of urinary catheterisation using silicone Foley's catheters did not influence the complication and symptom rates; hence silicon catheters can be placed in situ for up to 8 weeks before replacement instead of the traditional three-weekly change.

Modelling of vertical integration in commercial poultry production of Ghana: A count data model analysis.

Poultry production has significant potential to reduce protein deficiency, food insecurity and poverty in Ghana. However, limited vertical integration and high cost of production in the sector have stifled growth and exposed poultry farms in the country to many risks, leading to poor business performance. This study uses cross-sectional data from 102 commercial poultry farms to assess the determinants of vertical integration in the Ghanaian poultry industry by employing zero-inflated Poisson (ZIP) and Zero-inflated Negative Binomial (ZINB) models. The results show that one in every four poultry farms in the country are vertically integrated, either partially or fully. The ZINB model, which best fits the data, reveals that the degree of vertical integration in the poultry business is significantly influenced by a set of personal (education, occupation, and farming experience) and farm level (land tenure, flock size, production cost, and farm revenue) characteristics as well as institutional factors (credit access, extension access and membership of association). The paper discusses the implications of these findings and provides appropriate recommendations for strengthening the poultry industry in Ghana.

Occurrence and significance of fluoroquinolone-resistant and ESBL-producing Escherichia coli and Klebsiella pneumoniae complex of the rectal flora in Ghanaian patients undergoing prostate biopsy.

Background: Reports suggest that fluoroquinolone (FQ)-resistant and ESBL-producing rectal flora are associated with infectious complications in men undergoing transrectal ultrasound-guided prostate needle biopsy (TRUS-B). Objectives: We investigated the relationship between carriage of FQ-resistant and ESBL-producing Escherichia coli and Klebsiella pneumoniae complex of the rectal flora, and the 30 day incidence rate of post-TRUS-B infectious complications. Methods: From 1 January 2018 to 30 April 2019, rectal swabs of 361 patients were cultured pre-TRUS-B for FQ-resistant and ESBL-producing flora. Patients were followed up for 30 days for infectious complications post-biopsy. Multivariable logistic regression analyses were used to identify risk factors. Results: Overall, 86.4% (n = 312/361) and 62.6% (n = 226/361) of patients carried FQ-resistant and ESBL-producing E. coli and K. pneumoniae complex, respectively. Approximately 60% (n = 289/483) of the FQ-resistant and 66.0% (n = 202/306) of the ESBL-positive isolates exhibited in vitro resistance to the pre-biopsy prophylactic antibiotic regimen of levofloxacin and gentamicin. Amikacin and meropenem were the most effective antibiotics against the MDR rectal E. coli and K. pneumoniae complex (78.7% and 84.3%, respectively). The 30 day incidence rate for post-biopsy infections was 3.1% (n = 11/361), with an overall high probability (96.9%) of staying free of infections within the 30 day period post-TRUS-B. Antibiotic use in the previous 3 months was a risk factor for rectal carriage of FQ-resistant and ESBL-positive isolates. Rectal colonization by ESBL-positive E. coli and K. pneumoniae complex comprised an independent risk factor for post-biopsy infectious complications. Conclusions: The findings suggest that a change in prophylactic antibiotics to a more targeted regimen may be warranted in our institution.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

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.