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MedRxiv : the Preprint Server For... Apr 2024Deep learning models for variant pathogenicity prediction can recapitulate expert-curated annotations, but their performance remains unexplored on actual disease...
Deep learning models for variant pathogenicity prediction can recapitulate expert-curated annotations, but their performance remains unexplored on actual disease phenotypes in a real-world setting. Here, we apply three state-of-the-art pathogenicity prediction models to classify hereditary breast cancer gene variants in the UK Biobank. Predicted pathogenic variants in , and , but not and were associated with increased breast cancer risk. We explored gene-specific score thresholds for variant pathogenicity, finding that they could improve model performance. However, when specifically tasked with classifying variants of uncertain significance, the deep learning models were generally of limited clinical utility.
PubMed: 38633773
DOI: 10.1101/2024.04.05.24305402 -
Cancer Medicine Apr 2024Evidence of the impact of the COVID-19 pandemic on cancer prevention and control is growing, but little is known about patient-level factors associated with delayed...
PURPOSE
Evidence of the impact of the COVID-19 pandemic on cancer prevention and control is growing, but little is known about patient-level factors associated with delayed care. We analyzed data from a survey focused on Iowan cancer patients' COVID-19 experiences in the early part of the pandemic.
METHODS
Participants were recruited from the University of Iowa Holden Comprehensive Cancer Center's Patients Enhancing Research Collaborations at Holden (PERCH) program. We surveyed respondents on demographic characteristics, COVID-19 experiences and reactions, and delays in any cancer-related health care appointment, or cancer-related treatment appointments. Two-sided significance tests assessed differences in COVID-19 experiences and reactions between those who experienced delays and those who did not.
RESULTS
There were 780 respondents (26% response), with breast, prostate, kidney, skin, and colorectal cancers representing the majority of respondents. Delays in cancer care were reported by 29% of respondents. In multivariable-adjusted models, rural residents (OR 1.47; 95% CI 1.03, 2.11) and those experiencing feelings of isolation (OR 2.18; 95% CI 1.37, 3.47) were more likely to report any delay, where experiencing financial difficulties predicted delays in treatment appointments (OR 5.72; 95% CI 1.96, 16.67). Health insurance coverage and concern about the pandemic were not statistically significantly associated with delays.
CONCLUSION
These findings may inform cancer care delivery during periods of instability when treatment may be disrupted by informing clinicians about concerns that patients have during the treatment process. Future research should assess whether delays in cancer care impact long-term cancer outcomes and whether delays exacerbate existing disparities in cancer outcomes.
Topics: Humans; COVID-19; Delayed Diagnosis; Delivery of Health Care; Health Services Accessibility; Iowa; Neoplasms; Pandemics; Time-to-Treatment; Male; Female; Adolescent; Adult; Middle Aged; Aged; Aged, 80 and over
PubMed: 38629238
DOI: 10.1002/cam4.7183 -
Frontiers in Public Health 2024Benign prostatic hyperplasia (BPH) is a prevalent condition in older men, causing significant morbidity. Despite recent progress, essential concerns of the disease...
BACKGROUND
Benign prostatic hyperplasia (BPH) is a prevalent condition in older men, causing significant morbidity. Despite recent progress, essential concerns of the disease remain under-researched. This study aims to assess knowledge and estimate self-reported prevalence of BPH in Saudi Arabian men. Understanding BPH prevalence in Saudi Arabia is essential for healthcare planning, resource allocation, public awareness, early detection, intervention, research, and addressing regional variations.
METHOD
A cross-sectional study was conducted from February to May 2022 using a validated questionnaire. Univariate and multivariate statistical methods assessed knowledge of BPH among 559 adult Saudi men (mean age: 47.2 years) and its association with demographic variables.
RESULTS
The self-reported prevalence rate of BPH for Saudi Arabian men was 12.0%. Most adults (74.2%) were aware that BPH is a risk factor for prostate cancer and 75% were aware of the increased risk of BPH in older people. Furthermore, 44.5% of participants associated nocturia with BPH, while 76.6% related urinary tract infection (UTI) with BPH. The study demonstrated a significant association between BPH awareness and marital status ( = 0.02), level of education (p = 0.02), and employment status ( = 0.04).
CONCLUSION
While men in Saudi Arabia generally had sufficient knowledge about BPH, there was a knowledge gap regarding certain risk factors like obesity and cardiac diseases. To address this, an educational program should be developed for both the general population and those at high risk of BPH.
Topics: Male; Adult; Humans; Aged; Middle Aged; Saudi Arabia; Prostatic Hyperplasia; Cross-Sectional Studies; Self Report; Prevalence
PubMed: 38628856
DOI: 10.3389/fpubh.2024.1271816 -
PloS One 2024To analyse trends in urinary tract infection (UTIs) hospitalisation among patients adults 18-65 aged in Spain from 2000-2015. (Observational Study)
Observational Study
OBJECTIVE
To analyse trends in urinary tract infection (UTIs) hospitalisation among patients adults 18-65 aged in Spain from 2000-2015.
METHODS
Retrospective observational study using the Spanish Hospitalisation Minimum Data Set (CMBD), with codifications by the International Classification of Diseases (ICD-9). Variables: Type of UTIs (pyelonephritis, prostatitis, cystitis and non-specific-UTIs), sex, age (in 5 categories: 18-49 and 50-64 years in men, and 18-44, 45-55 and 56-64 years in women), comorbidity, length of stay, costs and mortality associated with admission. The incidence of hospitalisation was studied according to sex, age group and type of UTIs per 100,000. Trends were identified using Joinpoint regression.
RESULTS
From 2000-2015, we found 259,804 hospitalisations for UTIs (51.6% pyelonephritis, 7.5% prostatitis, 0.6% cystitis and 40.3% non-specific UTIs). Pyelonephritis predominated in women and non-specific UTIs in men. The hospital stay and the average cost (2,160 EUR (IQR 1,7872,540 were greater in men. Overall mortality (0.4%) was greater in non-specific UTIs. More women were admitted (rates of 79.4 to 81.7) than in men (30.2 to 41). The greatest increase was found in men aged 50-64 years (from 59.3 to 87). In the Joinpoint analysis, the incidence of pyelonephritis increased in women [AAPC 2.5(CI 95% 1.6;3.4)], and non-specific UTIs decreased [AAPC -2.2(CI 95% -3.3;-1.2)]. Pyelonephritis decreased in men [AAPC -0.5 (CI 95% -1.5;0.5)] and non-specific UTIs increased [AAPC 2.3 (CI 95% 1.9;2.6)] and prostatitis increased [AAPC 2.6 (CI 95% 1.4;3.7)].
CONCLUSIONS
The urinary infection-related hospitalisation rate in adults in Spain increased during the period 2000-2015. Pyelonephritis predominated in women and non-specific UTIs in men. The highest hospitalisation rates occurred in the women but the greatest increase was found in men aged 65-74. The lenght of stay and cost were higher in men.
Topics: Adult; Female; Humans; Male; Cystitis; Hospitalization; Prostatitis; Pyelonephritis; Spain; Urinary Tract Infections; Retrospective Studies
PubMed: 38626199
DOI: 10.1371/journal.pone.0298931 -
Translational Cancer Research Mar 2024Coronavirus disease 2019 (COVID-19) manifest differently depending on patients' background and pre-existing conditions. It remains unclear how African Americans with...
BACKGROUND
Coronavirus disease 2019 (COVID-19) manifest differently depending on patients' background and pre-existing conditions. It remains unclear how African Americans with cancer have been affected in comparison to those without. In this study, we aim to identify demographic, clinical, and laboratory markers associated with mortality in COVID-19 patients with cancer.
METHODS
We reviewed all COVID-19 hospitalized patients' records from Dec. 2019 to Oct. 2021 at Howard University Hospital. Patients having a history of, or active, cancer were reviewed. Clinical, treatment, lab test values, and pathological data were extracted. Univariable and multivariable analyses were conducted on the entire cohort as well as on cases and controls separately, using SPSS software.
RESULTS
Out of 512 COVID-19 infected patients, 49 had cancer, either active or history of cancer (cases) and 463 COVID-19 were cancer-free (controls), allowing for comparison. African American race was predominant in both cases and controls, 83.7% and 66.7% respectively. Cancer patients were older than non-cancer patients (mean age: 70.6 56.3 years) and had an increased length of hospital stay (mean 13.9 9.4 days). Mortality is significantly higher among cancer patients (n=10, 20.4%, P=0.03) compared to non-cancer COVID-19 patients (n=41, 8.9%). Among cancer patients, breast cancer was more prevalent in females and prostate cancer in males (54% and 52%, respectively). A comparison of patients with active previous cancer showed no significant difference in the clinical outcome, death discharge (P=0.34). A higher reduction in albumin level in cancer cases, from the time of admission to day 5, was significantly associated with death during the hospital stay compared to those discharged (n=24, 49.0%, P<0.001). In controls, lymphopenia (n=436, 94.2%, P=0.05), aspartate aminotransferase (AST) (n=59, 12.7%, P=0.008) and albumin (n=40, 8.6%, P=0.02) have shown an association with increased mortality.
CONCLUSIONS
Albumin level has an inverse relationship with clinical outcomes among all COVID-19 infected cancer patients. Reduction in albumin level during the hospital stay, particularly in COVID-19 cancer patients should be considered as a predictor of mortality. Further research with a large cohort size is needed to verify and identify other predictors of outcomes in COVID-19 patients with cancer.
PubMed: 38617523
DOI: 10.21037/tcr-23-166 -
Chinese Medical Journal Jun 2024Given the recent updates in cancer burden estimates by GLOBOCAN 2022, this study was undertaken to provide pertinent perspectives within the context of the Human...
BACKGROUND
Given the recent updates in cancer burden estimates by GLOBOCAN 2022, this study was undertaken to provide pertinent perspectives within the context of the Human Development Index (HDI) and major world economies.
METHODS
Datasets sourced from GLOBOCAN encompassed cancer cases and deaths across all cancer types in 2022, alongside projections up to 2050. Cancer incidences and deaths of the top 10 cancers within China and four distinct HDI-classified regions were compared using descriptive analyses. Age-standardized incidence rates (ASIRs) and mortality rates (ASMRs) worldwide for the most prevalent cancers in 2022 across ten largest economies and four-tier HDIs were examined. The top five cancer types concerning both incidence and mortality in China were delineated by sex and age group.
RESULTS
In males, prostate cancer predominated in countries with low, high (except China), and very high HDI. Prostate and liver cancers were prominent causes of death in countries with low HDI. In females, breast and cervical cancers predominated in countries with low-to-medium HDI. Lung and colorectal cancer incidence and deaths increased with high HDI for both sexes. ASIRs and ASMRs for breast, prostate, lung, and colorectal cancers in the top 10 economies were higher than the global average. However, liver, stomach, and cervical cancers in most Western countries exhibited lower rates. In China, hematologic malignancies (43%) were prevalent among children aged 0-14 years, whereas thyroid cancer led among adolescents and young adults aged 15-39 years. Regarding incidence and mortality, lung cancer predominated for individuals over 40 years, except for females aged 40-59 years, in whom breast cancer predominated. Projected trends indicated substantial increases in new cancer cases (76.6%) and deaths (89.7%) over the next three decades.
CONCLUSIONS
Infection- and poverty-related cancer burdens are offset by increased prostate, breast, colorectal, and lung cancer incidence associated with rapid societal and economic transitions. Cancer incidence and mortality patterns in China feature characteristics of developed and developing countries, necessitating tailored, evidence-based, and comprehensive strategies for effective cancer prevention and control.
Topics: Humans; Male; Neoplasms; Female; Incidence; China; Socioeconomic Factors; Adult; Middle Aged
PubMed: 38616547
DOI: 10.1097/CM9.0000000000003140 -
Canadian Urological Association Journal... Apr 2024We aimed to compare holmium laser enucleation of the prostate (HoLEP) outcomes in patients with and without neurologic diseases (ND).
INTRODUCTION
We aimed to compare holmium laser enucleation of the prostate (HoLEP) outcomes in patients with and without neurologic diseases (ND).
METHODS
A prospectively maintained database of patients undergoing HoLEP from January 2021 to April 2022 was reviewed. The following NDs were included: diabetes-related neuropathy/neurogenic bladder, Parkinson's disease, dementia, cerebrovascular accident, multiple sclerosis, traumatic brain injury, transient ischemic attack, brain/spinal tumors, myasthenia gravis, spinal cord injury, and other. Statistical analysis was performed using t-tests, Chi-squared, and binomial tests (p<0.05).
RESULTS
A total of 118 ND patients were identified with 135 different neurologic diseases. ND patients were more likely to have indwelling catheters (57% vs. 39%, p=0.012) and urinary tract infections (UTIs) preoperatively (32% vs. 19%, p=0.002). Postoperatively, ND patients were more likely to fail initial trial of void (20% vs. 8.1%, p<0.001) and experience an episode of acute urinary retention (16% vs. 8.5%, p=0.024). Within 90 days postoperative, the overall complication rate was higher in the ND group (26% vs. 13%, p=0.001). Within the ND group, 30/118 (25%) had ≥1 UTI within 90 days preoperative, which decreased to 10/118 (8.7%) 90 days postoperative (p<0.001). At last followup (mean 6.7 months [ND] vs. 5.4 months [non-ND], p=0.03), four patients (4.4%) in the ND group required persistent catheter/clean intermittent catheterization compared to none in the non-ND group (p=0.002).
CONCLUSIONS
Patients with ND undergoing HoLEP are more likely to experience postoperative retention and higher complication rates compared to non-ND patients. While UTI rates are higher in this population, HoLEP significantly reduced three-month UTI and catheterization rates.
PubMed: 38587977
DOI: 10.5489/cuaj.8683 -
Cureus Mar 2024Urethroplasty using a buccal mucosa graft (BMG) and a preputial skin flap (PSF) are two common techniques used for the treatment of anterior urethral stricture. The...
BACKGROUND
Urethroplasty using a buccal mucosa graft (BMG) and a preputial skin flap (PSF) are two common techniques used for the treatment of anterior urethral stricture. The present study compared the efficacy of these two techniques on the basis of success rate, preservation of sexual function, and complications.
MATERIALS AND METHODS
This prospective, randomized, interventional study was conducted on adult male patients diagnosed with non-obliterative anterior urethral strictures of length >2 cm from August 2021 to December 2022. Pre-operative and post-operative work-up done included assessment of the International Prostate Symptom Score (IPSS), Quality of Life (QOL), International Index of Erectile Function (IIEF) Score, Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EJD), Bother score, Urethral Stricture Surgery-Patient-Related Outcome Measure (USS-PROM), and peak urinary flow rate (Qmax) for each patient. Post-operative values for each score were compared with pre-operative values.
RESULTS
Out of 31 patients, 16 underwent BMG urethroplasty, and 15 underwent PSF urethroplasty. The most common cause of stricture in both groups was idiopathic (35.5% and 53.3%). A statistically significant increase in IIEF score was observed in the BMG group in comparison to the PSF group (P<0.0001). The mean IPPS score in USS-PROM has shown a significant drop in BMG (19.6 vs. 17.3; P = 0.020). Hemoglobin drop was significantly higher in PSF than in BMG (2.6 vs. 1.9; P = 0.011). A higher incidence of surgical site infection was reported in the PSF group than in the BMG group (46.7% vs. 12.5%). The average operative time for surgery was higher in PSF than in BMG (154.8 min vs. 145.0 min), respectively. Each group had one patient with a recurrence.
CONCLUSION
Both techniques are equally good for urethral reconstruction (UR); however, improvement of sexual function is more in favor of the BMG urethroplasty group.
PubMed: 38586660
DOI: 10.7759/cureus.55732 -
Lancet (London, England) May 2024Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and...
Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.
BACKGROUND
Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations.
METHODS
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds.
FINDINGS
The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles.
INTERPRETATION
Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Humans; Life Expectancy; Cause of Death; Global Burden of Disease; Female; COVID-19; Male; Aged; Middle Aged; Adult; Child, Preschool; Infant; Global Health; Adolescent; Young Adult; Child; Aged, 80 and over; SARS-CoV-2; Infant, Newborn; Pandemics
PubMed: 38582094
DOI: 10.1016/S0140-6736(24)00367-2 -
Scientific Reports Apr 2024Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated...
Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p < 0.001) at a rate of 77.9%, but no significant difference was observed when compared to group 4. In the relationship between TWIST1/Vimentin methylation and clinicopathological features of BC patients from our center, we found there was no significant association between TWIST1/Vimentin status and proteinuria and/or hematuria, and hypermethylation of TWIST1 / VIM genes was found in both high and low tumor grade and in both non-muscle invasive bladder cancer (stages Tis, Ta, or T1) and muscle-invasive bladder cancer (stage T2 or above). In the multivariable analysis for cancer detection, a positive TWIST1/Vimentin methylation were significantly linked to a heightened risk of BC. Moreover, TWIST1/Vimentin promoter methylation demonstrated an ability to detect BUC in urine samples with a sensitivity of 78% and a specificity of 83%. Our findings reveal that hypermethylation of the TWIST1/Vimentin promoter occurs in bladder urothelial carcinoma, and its high sensitivity and specificity suggest its potential as a screening and therapeutic biomarker for urothelial carcinoma of the bladder.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urinary Bladder; Vimentin; Biomarkers, Tumor; DNA Methylation; Nuclear Proteins; Twist-Related Protein 1
PubMed: 38575639
DOI: 10.1038/s41598-024-58586-7