Man's Burden Research Articles

Global trends and projections of occupational trichloroethylene (TCE) exposure-associated kidney cancer: Insights of the Global Burden of Disease (GBD) Study 2021 from 1990 to 2021 and prediction to 2050

BackgroundExposure to trichloroethylene (TCE) in occupations is associated with an increased risk of kidney cancer (KC). However, there is a lack of comprehensive study on the global burden of occupational exposure to TCE-related KC. MethodsEpidemiological data on occupational TCE exposure-associated KC from 1990 to 2021 were obtained from Global Burden of Disease (GBD) 2021 study, including death counts and disability-adjusted life years (DALYs). Global burden of this disease was stratified by genders, age, socio-demographic index (SDI) quintiles, GBD subcontinental regions, and countries. The estimated annual percentage change (EAPC) was calculated to illustrate trends over the last 32 years, and forecasts were conducted to predict the disease burden until 2050. ResultsIn 2021, the global age-standardized death rate (ASDR) of occupational TCE exposure-related KC was 0.0009 (95 %UI: 0.0002–0.0016) per 100,000 persons, and the age-standardized DALY rate (ASDAR) was 0.0284 (95 %UI: 0.0062–0.0522) per 100,000 individuals. The disease showed significant heterogeneity by sex and age, with males bearing a notably higher burden, and the burden being concentrated in the 50–79 year-old group. Major burdens were focused in middle to high-middle SDI regions, especially in Southern Latin America (Uruguay, Argentina, and Chile). Over 32 years, the burden of occupational TCE exposure-associated KC has gradually increased, with projections indicating continued growth to 2050, particularly among males and individuals aged 50–79. Regions like high-middle SDI areas, North America, High-income North America, Southern Sub-Saharan Africa, saw the most significant increases. Correlation analyses indicated a positive association between ASDR and ASDAR with SDI, while EAPC showed a notable negative correlation with SDI. Decomposition analyses reveals three global population determinants that positively contributed to the increase in deaths, but negatively impacted DALYs. ConclusionThis study highlights a significant rising trend of occupational TCE exposure-associated KC from 1990 to 2021 and projected to 2050, with an emphasis on the disease burden in men, elderly population, and middle to high-middle SDI regions, underscoring the impact of occupational TCE exposure on KC.

Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on APOE4 Homozygosity in Alzheimer's Disease.

Sex differences in patterns of cortical thickness and neuropsychiatric symptom (NPS) burden were examined among individuals with Alzheimer's disease (AD) and two copies (homozygote carriers) of the e4 allele of the apolipoprotein gene (APOE). A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within- and between-sex differences in gray-matter cortical thickness and total NPS burden associated with APOE homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial-lateral temporal regions and a greater burden of NPS, relative to both non-homozygous females and homozygous males. These findings support the notion that APOE4 status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally.

Time to level the playing field between men and women — Given similar injury incidence: A two-season analysis of match injuries in elite men and women's (Super League) rugby league

ObjectivesTo compare match injury incidence, severity and burden in men's and women's elite rugby league. DesignA prospective cohort epidemiological study. MethodsTime loss match injury data were collected from all men's (11,301 exposure hours) and women's (5,244 exposure hours) Super League clubs. ResultsInjury incidence and burden were not different between men and women (mean [95 % CI]; 54 [45 to 65] vs. 60 [49 to 74] per 1000 match-hours; p = 0.39, and 2332 [1844 to 2951] vs. 1951 [1560 to 2440] days lost per 1000 match-hours; p = 0.26). However, injury severity was greater for men than women (42 [35–50] vs. 35 [29 to 42]; p = 0.01). Lower limbs accounted for 54 % and 52 % of injuries for men and women, with the head/face the most frequently injured location due to concussion (12 [10 to 15] and 10 [8 to 14] per 1000 match-hours for men and women). Injuries to the knee had the greatest burden for men and women (708 [268–1868] and 863 [320–2328] days lost per 1000 match-hours). Being tackled was the most common injury mechanism for men and women (28 % and 38 %) with greater burden (p < 0.01) than other injury mechanisms. ConclusionsMale and female rugby league players have similar injury incidence and burden; however, injury severity was higher in men. Head/face injuries have the highest injury incidence and knee injuries have the highest burden. These injuries should be the focus for prevention initiatives at a league (via laws), player, and coach level, with equal and specific focus for both men's and women's rugby league players.

Racial Ideologies and Imperial Discourses: A New Historicist Reading of Kipling’s “The White Man’s Burden”

Set against the backdrop of the 19th-century apex of European colonial expansion and formation of New Imperialism, Rudyard Kipling's "The White Man's Burden", composed in 1899, emerges as a cultural artefact reflecting and actively participating in the racial and imperialistic discourses prevalent during this epoch. Generally criticized for perpetuating a one-sided narrative, the poem ignores the violence, exploitation, and cultural disruption wrought by colonial powers and presents an idealized vision of the colonizers' mission without acknowledging the harsh realities faced by the colonized. The present article offers a comprehensive New Historicist examination of Kipling's iconic poem by contextualizing it within the racial and exceptionalist socio-political and pseudoscientific milieu of the late 19th century United Kingdom and the complex web of imperial ideologies prevalent in the Victorian era. By engaging critically with Kipling's poem, this study aims to give insights into the intersections between literature, power, and historical context and offer a nuanced understanding of the legacies of imperialistic ideologies and their implications for our present-day understanding of empire and race.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and itsassociated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, andinterventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

Statistical analysis of disability-adjusted life years for stomach and colorectal cancers in Changning District of Shanghai

Objectives: To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district. Methods: Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods. Results: The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/105 and 597.51/105, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions: The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

The Divine Mandate of Colonialism: Orientalism in Wilkie Collins’s 'The Black Robe'

In postcolonial studies, the missionary is inevitably associated with colonialism. This is explained by the fact that the missionaries’ main task was to spread Christianity by preaching the “blessings of civilisation” and implementing “the white man's burden”. This study adopts Edward W. Said's Orientalist discourse to critique the construct of the representation of indigenous peoples in Wilkie Collins's (1824-1889) The Black Robe (1881). Said's ideas are particularly instrumental in critically analysing the Western (mis)representation of Native Americans as savages who need to be civilised. The Black Robe is a partly epistolary novel revolving around a series of unfortunate events by Lewis Romayne, whose remorse for the accidental murder of a young man haunts him for the rest of his life. This research reveals inconsistencies regarding the author's religious views in the novel. It is argued that while Collins's anti-Catholic sarcasm aims to expose the corruption of religious orders, this attitude does not apply to colonial discourse. Rather, Catholicism is purposefully used as a divisive imperialist tool in the novel, and therefore the missionaries serve as colonial agents who “bless” discriminatory acts of British imperial policy, hence the image of the black robe that represents the colonial legacy consolidating the influence of British imperial power through religion. In The Black Robe, indigenous peoples are described as “bloodthirsty savages” and it is believed that their souls can be saved under the influence of Christianity. This enforcement also represents colonial hegemony, through which American Indians are subjected to social and cultural assimilation. The ideology of white racial supremacy manifests itself in the justification of the colonial missions, which claim that they have legitimate and religious rights over the land and culture of the natives.

Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140,000 subjects.

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant associations with PCa risk, including 16 previously reported proteins and eight novel proteins. Of them, 14 proteins showed negative associations and 10 showed positive associations with PCa risk. For 18 of the identified proteins, potential functional somatic changes of encoding genes were detected in PCa patients in The Cancer Genome Atlas (TCGA). Genes encoding these proteins were significantly involved in cancer-related pathways. We further identified drugs targeting the identified proteins, which may serve as candidates for drug repurposing for treating PCa. In conclusion, this study identifies novel protein biomarker candidates for PCa risk, which may provide new perspectives on the etiology of PCa and improve its therapeutic strategies.

Role of Neck Vessel Doppler in Correlation with Coronary CT Angiography for Assessing Coronary Artery Disease Burden in Diabetic Women and Men

Objectives: With an incidence of 4.1 for women and 6.4 for men/1000 person-years, cardiovascular disease is the primary cause of morbidity and mortality for both men and women worldwide.[1] In asymptomatic patients, subclinical atherosclerosis has been detected utilising several non-invasive methods, such as computed tomography (CT) coronary angiography and Neck Vessel Doppler (NVD) to test coronary calcification. The goal of the present study was to assess the role of NVD in correlation with coronary CT angiography (CCTA) in assessing the coronary artery disease (CAD) burden in diabetic women and men patients. Materials and Methods: This study was conducted on 30 female patients and 30 male patients aged 40–60 years, who were referred for CCTA for suspected CAD at Nizam’s Institute of Medical Sciences Hospital, Hyderabad. This study was an observational and prospective study of diabetes mellitus patients. All subjects underwent NVD and CCTA scan on the same day. Carotid intimal media thickness (CIMT) was considered the largest of the two separate values (left and right CIMT). The analysis examined factors associated with coronary artery calcification defined as a coronary artery calcium (CAC) score &gt;0. Results: The mean age at assessment was 52.6 years in the diabetic male group and 53.7 in the diabetic female group. 63% of the study population was also hypertensive in the male group and 77% of the study population was also hypertensive in the female group. Mean CIMT was 1.01 mm in the diabetic male group and 1.02 mm in the diabetic female group. Twenty-two (73.3%) patients in the diabetic male group had a CAC score &gt;0, of which 4 (18.18%) had severe coronary artery calcification (CAC score &gt;400 Au), 7 (31.81%) had moderate coronary artery calcification (CAC score 100–400 Au), 11 (50%) had mild coronary artery calcification (CAC score 1-99 Au), and 8 out of 30 (26.67%) had no coronary artery calcification (CAC score &lt;0 Au). Twenty (66.67%) patients in the diabetic female group had a CAC score &gt;0, of which 2 (10%) had severe coronary artery calcification (CAC score &gt;400 Au), 7 (35%) had moderate coronary artery calcification (CAC score 100–400 Au), 11 (55%) had mild coronary artery calcification (CAC score 1-99Au) and 10 out of 30 (33.33%) had no coronary artery calcification (CAC score &lt;0 Au). Mean CIMT and carotid plaque were significantly associated with CAC (P = 0.046 and P = 0.026, respectively, in the diabetic male’s group and P = 0.008 and P = 0.011, respectively, in the diabetic female’s group). The significance was more profound in the diabetic female group when compared to the diabetic male group. Conclusion: NVD giving various surrogate parameters such as CIMT and plaque, in correlation with CCTA (CAC score), can play a significant role in assessing the CAD burden in men and women with diabetes and hypertension, thereby helping the clinician to assess the future risk for stroke or myocardial ischemic events to take active interventions.

Associations of alcohol intake with subclinical carotid atherosclerosis in 22,000 Chinese adults

Background and aimsWe investigated the causal relevance of alcohol intake with measures of carotid artery thickness and atherosclerosis in Chinese adults. MethodsThe study included 22,384 adults from the China Kadoorie Biobank, with self-reported alcohol use at baseline and resurvey, carotid artery ultrasound measurements, and genotyping data for ALDH2-rs671 and ADH1B-rs1229984. Associations of carotid intima media thickness (cIMT), any carotid plaque, and total plaque burden (derived from plaque number and size) with self-reported (conventional analyses) and genotype-predicted mean alcohol intake (Mendelian randomization) were assessed using linear and logistic regression models. ResultsOverall 34.2% men and 2.1% women drank alcohol regularly at baseline. Mean cIMT was 0.70 mm in men and 0.64 mm in women, with 39.1% and 26.5% having carotid plaque, respectively. Among men, cIMT was not associated with self-reported or genotype-predicted mean alcohol intake. The risk of plaque increased significantly with self-reported intake among current drinkers (odds ratio 1.42 [95% CI 1.14–1.76] per 280 g/week), with directionally consistent findings with genotype-predicted mean intake (1.21 [0.99–1.49]). Higher alcohol intake was significantly associated with higher carotid plaque burden in both conventional (0.19 [0.10–0.28] mm higher per 280 g/week) and genetic analyses (0.09 [0.02–0.17]). Genetic findings in women suggested the association of genotype-predicted alcohol with carotid plaque burden in men was likely to due to alcohol itself, rather than pleiotropic genotypic effects. ConclusionsHigher alcohol intake was associated with a higher carotid plaque burden, but not with cIMT, providing support for a potential causal association of alcohol intake with carotid atherosclerosis.

EPH30 Burden of HPV-Associated Cancers Among Men in Ecuador, 2015-2019

In Latin America, the human papillomavirus (HPV) attributable fraction (AF) in cancers of the penis, anus, and head and neck (H&N) are estimated in 50%, 88%, and 25%, respectively. The HPV-AF of these cancers could be eliminated if HPV infection is prevented (e.g.vaccination). In Ecuador, the HPV vaccination program targets only 9-10-year girls. Since data on HPV-associated cancer burden in men are not available in Ecuador, we assessed real-world evidence using local databases.

Differences in the global exposure, mortality and disability of low bone mineral density between men and women: the underestimated burden in men

Talking about osteoporosis, we tend to focus on post-menopause women who are at increased risk due to estrogen depletion, while less attention has been paid to the disease in men. Currently, there is a lack of understanding about the difference of osteoporosis incidence and burden by sex. In this study, we used data from the Global Burden of Disease Study 2019 (GBD 2019) to compare the difference in the prevalence and burden of low bone mineral density (LBMD) between men and women, by location, year, age and socio-demographic index. We found the prevalence of LBMD was higher in women than in men. However, the age standardized mortality rate was greatly higher in men than in women. Using disability-adjusted life year (DALY) to measure the burden, we also observed higher age standardized DALY rate in men. Using sociodemographic index (SDI) as the measure of social development level, we found that higher mortality and DALY rates were mainly seen in middle and high SDI countries. Falls were the leading cause for of deaths and disabilities in both men and women with LBMD, followed by transport injuries. Fall-related mortality was higher in women, while transport injuries caused more deaths and disabilities in men. Conclusively, more attention should be paid to osteoporosis in men, and related policies, clinical practices, and guidelines are in need to reduce the burden of LBMD and osteoporosis in men.

Nasopharyngeal Carcinoma Burden and Its Attributable Risk Factors in China: Estimates and Forecasts from 1990 to 2050.

Nasopharyngeal carcinoma (NPC) is an uncommon and aggressive malignant head and neck cancer, which is highly prevalent in southern and southwestern provinces in China. The aim of this study was to examine the disease burden and risk factors of nasopharyngeal carcinoma in China from 1990 to 2019 and to predict the incidence trends from 2020 to 2049. All data were extracted from the 2019 Global Burden of Disease (GBD) study. Joinpoint regression and age-period-cohort (APC) models were chosen to analyze prevalence trends. The temporal trends and age distribution of risk factors were also analyzed descriptively. Bayesian APC models were used to predict the prevalence from 2020 to 2049. The results indicate a higher disease burden in men and older adults. Their attributable risk factors are smoking, occupational exposure to formaldehyde, and alcohol use. We predict that the incidence will be on the rise in all age groups between 2020 and 2049, with the highest incidence in people aged 70 to 89 years. In 2049, the incidence rate is expected to reach 13.39 per 100,000 (50-54 years), 16.43 (55-59 years), 17.26 (60-64 years), 18.02 (65-69 years), 18.55 (70-74 years), 18.39 (75-79 years), 19.95 (80-84 years), 23.07 (85-89 years), 13.70 (90-94 years), and 6.68 (95+ years). The findings of this study might deserve consideration in China's NPC prevention and control policy design.

The Burden of Disease in Germany at the National and Regional Level.

.Summary measures such as disability-adjusted life years (DALY) are becoming increasingly important for the standardized assessment of the burden of disease due to death and disability. The BURDEN 2020 pilot project was designed as an independent burden-of-disease study for Germany, which was based on nationwide data, but which also yielded regional estimates. DALY is defined as the sum of years of life lost due to death (YLL) and years lived with disability (YLD). YLL is the difference between the age at death due to disease and the remaining life expectancy at this age, while YLD quantifies the number of years individuals have spent with health impairments. Data are derived mainly from causes of death statistics, population health surveys, and claims data from health insurers. In 2017, there were approximately 12 million DALY in Germany, or 14 584 DALY per 100 000 inhabitants. Conditions which caused the greatest number of DALY were coronary heart disease (2321 DALY), low back pain (1735 DALY), and lung cancer (1197 DALY). Headache and dementia accounted for a greater disease burden in women than in men, while lung cancer and alcohol use disorders accounted for a greater disease burden in men than in women. Pain disorders and alcohol use disorders were the leading causes of DALY among young adults of both sexes. The disease burden rose with age for some diseases, including cardiovascular diseases, dementia, and diabetes mellitus. For some diseases and conditions, the disease burden varied by geographical region. The results indicate a need for age- and sex-specific prevention and for differing interventions according to geographic region. Burden of disease studies yield comprehensive population health surveillance data and are a useful aid to decision-making in health policy.

Worldwide cancer statistics of adults over 75 years old in 2019: a systematic analysis of the global burden of disease study 2019

Background and purposeCancer has become one of the major killers of humanity due to the number of people over the age of 75 increasing with population ageing. The aim of this study was to analyse the incidence and mortality rates in people over 75 of 29 cancer types in 204 countries and regions, as well as the trends from 1990 to 2019.MethodsTwenty-nine cancer types were collected from the Global Burden of Disease (GBD) 2019 database(https://vizhub.healthdata.org/gbd-results/). We collected global cancer data for 2019 in terms of sex, age, sociodemographic index (SDI), region, etc. The estimated annual percentage change (EAPC) was calculated to assess the trend of the cancer incidence and mortality rate from 1990 to 2019.ResultsIn 2019, the number of new cancer cases and deaths among people 75 and older was almost 3 and 4.5 times that of 1990, respectively. From 1990 to 2019, there was a slow rise in incidence and a slight decline in mortality. There were significant differences in the cancer burden based on sex, age, region, and SDI. The cancer burden in men was higher than in women. In addition, the cancer burden varied from region to region. The highest cancer burden occurred in high-income North America. In addition, the higher the SDI was, the greater the burden of cancer. The incidence of cancer in high SDI was approximately seven times that of low SDI, and the trend of increase in high SDI was obvious. However, the trend of mortality in high SDI was decreasing, while it was increasing in low SDI.ConclusionsThe present study focused on the cancer burden in adults over 75 years old. The findings in the study could serve as the basis for an analysis of the types of cancers that are most prevalent in different regions. This is beneficial for strategies of prevention and treatment according to the characteristics of different countries and regions to reduce the burden of cancer in older adults.

SC8 - Reliability of 68Ga-PSMA PET/CT in assessing real nodal burden in men with cN1 disease: clinical implications for patient counselling and multi-modal treatments

SC8 - Reliability of 68Ga-PSMA PET/CT in assessing real nodal burden in men with cN1 disease: clinical implications for patient counselling and multi-modal treatments

“Send Forth the Very Best Ye Breed”: Captain Frederick S. Wild and the War in the Philippines, 1899–1902

“Send Forth the Very Best Ye Breed”: Captain Frederick S. Wild and the War in the Philippines, 1899–1902

ON INTERSEMIOTIC SHIFT IN JUNGLE BOOK: FROM PAPER TO SCREEN

Translation theorists, see “translation as an active reconstitution of a foreign text mediated by irreducible linguistic, discursive and ideological differences of the target language culture.” Children's literature requires essential adjustments according to the receiving culture audience. Taking the connotation of adaptation as intersemiotic translation into account,the study centers on the classic animation series that went on air --- The Jungle Book in Hindi --- on Indian television in October 1989. The series was an adaptation of Rudyard Kipling's The Jungle Book. Several modifications took place in Kipling's sinister original text. Anime makes an attempt to negotiate between colonial undertones and domestication of the tale,posing a question on the authoritative voice of “White Man's Burden.”.Foucault stresses that the author's function historically changes over time.“Adaptation”--- usually viewed as “free translation”--- is an ambivalent activity that gives enough freedom to ensure what Walter Benjamin calls “the after-life of the original”.

Population benefits of addressing programmatic and social determinants of gender disparities in tuberculosis in Viet Nam: A modelling study.

High prevalence of infectious tuberculosis among men suggests potential population-wide benefits from addressing programmatic and social determinants of gender disparities. Utilising a sex-stratified compartmental transmission model calibrated to tuberculosis burden estimates for Viet Nam, we modelled interventions to increase active case finding, to reduce tobacco smoking, and to reduce alcohol consumption by 2025 in line with national and global targets. For each intervention, we examined scenarios differentially targeting men and women and evaluated impact on tuberculosis morbidity and mortality in men, women, and children in 2035. Active case finding interventions targeting men projected greater reductions in tuberculosis incidence in men, women, and children (16.2%, uncertainty interval, UI, 11.4-23.0%, 11.8%, UI 8.0-18.6%, and 21.5%, UI 16.9-28.5%, respectively) than those targeting women (5.2%, UI 3.8-7.1%, 5.4%, UI 3.9-7.3%, and 8.6%, UI 6.9-10.7%, respectively). Projected reductions in tuberculosis incidence for interventions to reduce male tobacco smoking and alcohol consumption were greatest for men (17.4%, UI 11.8-24.7%, and 11.0%, UI 5.4-19.4%, respectively), but still substantial for women (6.9%, UI 3.8-12.5%, and 4.4%, UI 1.9-10.6%, respectively) and children (12.7%, UI 8.4-19.0%, and 8.0%, UI 3.9-15.0%, respectively). Comparable interventions targeting women projected limited impact, with declines of 0.3% (UI 0.2%-0.3%) and 0.1% (UI 0.0%-0.1%), respectively. Addressing programmatic and social determinants of men's tuberculosis burden has population-wide benefits. Future interventions to increase active case finding, to reduce tobacco smoking, and to reduce harmful alcohol consumption, whilst not ignoring women, should focus on men to most effectively reduce tuberculosis morbidity and mortality in men, women, and children.

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1

BackgroundTalazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations. ObjectiveTo evaluate patient-reported health-related quality of life (HRQoL) and pain in patients who received talazoparib in the TALAPRO-1 study, with a special interest in patients harboring breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. Design, setting, and participantsTALAPRO-1 is a single-arm, phase 2 study in men with mCRPC DDR alterations either directly or indirectly involved in HRR, who previously received one to two taxane-based chemotherapy regimens for advanced prostate cancer and whose mCRPC progressed on one or more novel hormonal agents. Outcome measurements and statistical analysisMen completed the European Quality-of-life Five-dimension Five-level scale (EQ-5D-5L), EQ-5D visual analog scale (VAS), and Brief Pain Inventory—Short Form at predefined time points during the study. The patient-reported outcome (PRO) population included men who completed a baseline and one or more postbaseline assessments before study end. Longitudinal mixed-effect models assuming an unstructured covariance matrix were used to estimate the mean (95% confidence interval [CI]) change from baseline for pain and general health status measurements among all patients and patients with BRCA1/2 mutations. Results and limitationsIn the 97 men in the PRO population treated with talazoparib (BRCA1/2, n = 56), the mean (95% CI) EQ-5D-5L Index improved (all patients, 0.05 [0.01, 0.08]; BRCA1/2 subset, 0.07 [0.03, 0.10]), as did the EQ-5D VAS scores (all patients, 5.42 [2.65, 8.18]; BRCA1/2 subset, 4.74 [1.07, 8.41]). Improvements in the estimated overall change from baseline (95% CI) in the mean worst pain were observed in all patients (–1.08 [–1.52, –0.65]) and the BRCA1/2 subset (–1.15 [–1.67, –0.62]). The probability of not having had experienced deterioration of worst pain by month 12 was 84% for all patients and 83% for the BRCA1/2 subset. ConclusionsIn heavily pretreated men with mCRPC and DDR/HRR alterations, talazoparib was associated with improved HRQoL in all patients and the BRCA1/2 subset. In both patient groups, worst pain improved from baseline and the probability of not experiencing a deterioration in worst pain with talazoparib was high. Patient summaryWe show that talazoparib was associated at least with no change or improvements in health-related quality of life (HRQoL) and pain burden in men with metastatic castration-resistant prostate cancer and DNA damage response/homologous recombination repair gene alterations in the TALAPRO-1 study. These findings in patient-reported HRQoL and pain complement the antitumor activity and tolerability profile of talazoparib.