Annual Report to the Nation on the Status of Cancer, part 2: Early assessment of the COVID-19 pandemic's impact on cancer diagnosis.

BACKGROUND: With access to cancer care services limited because of coronavirus disease 2019 control measures, cancer diagnosis and treatment have been delayed. The authors explored changes in the counts of US incident cases by cancer type, age, sex, race, and disease stage in 2020. METHODS: Data were extracted from selected US population-based cancer registries for diagnosis years 2015-2020 using first-submission data from the North American Association of Central Cancer Registries. After a quality assessment, the monthly numbers of newly diagnosed cancer cases were extracted for six cancer types: colorectal, female breast, lung, pancreas, prostate, and thyroid. The observed numbers of incident cancer cases in 2020 were compared with the estimated numbers by calculating observed-to-expected (O/E) ratios. The expected numbers of incident cases were extrapolated using Joinpoint trend models. RESULTS: The authors report an O/E ratio <1.0 for major screening-eligible cancer sites, indicating fewer newly diagnosed cases than expected in 2020. The O/E ratios were lowest in April 2020. For every cancer site except pancreas, Asians/Pacific Islanders had the lowest O/E ratio of any race group. O/E ratios were lower for cases diagnosed at localized stages than for cases diagnosed at advanced stages. CONCLUSIONS: The current analysis provides strong evidence for declines in cancer diagnoses, relative to the expected numbers, between March and May of 2020. The declines correlate with reductions in pathology reports and are greater for cases diagnosed at in situ and localized stage, triggering concerns about potential poor cancer outcomes in the coming years, especially in Asians/Pacific Islanders. PLAIN LANGUAGE SUMMARY: To help control the spread of coronavirus disease 2019 (COVID-19), health care organizations suspended nonessential medical procedures, including preventive cancer screening, during early 2020. Many individuals canceled or postponed cancer screening, potentially delaying cancer diagnosis. This study examines the impact of the COVID-19 pandemic on the number of newly diagnosed cancer cases in 2020 using first-submission, population-based cancer registry database. The monthly numbers of newly diagnosed cancer cases in 2020 were compared with the expected numbers based on past trends for six cancer sites. April 2020 had the sharpest decrease in cases compared with previous years, most likely because of the COVID-19 pandemic.

Enhancing involvement of people with multiple sclerosis in clinical trial design.

BACKGROUND: Although often overlooked, patient and public involvement (PPI) is vital when considering the design and delivery of complex and adaptive clinical trial designs for chronic health conditions such as multiple sclerosis (MS). METHODS: We conducted a rapid review to assess current status of PPI in the design and conduct of clinical trials in MS over the last 5 years. We provide a case study describing PPI in the development of a platform clinical trial in progressive MS. RESULTS: We identified only eight unique clinical trials that described PPI as part of articles or protocols; nearly, all were linked with funders who encourage or mandate PPI in health research. The OCTOPUS trial was co-designed with people affected by MS. They were central to every aspect from forming part of a governance group shaping the direction and strategy, to the working groups for treatment selection, trial design and delivery. They led the PPI strategy which enabled a more accessible, acceptable and inclusive design. CONCLUSION: Active, meaningful PPI in clinical trial design increases the quality and relevance of studies and the likelihood of impact for the patient community. We offer recommendations for enhancing PPI in future MS clinical trials.

Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy.

BACKGROUND: Gut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal ß-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH. METHODS: Eighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1-3-ß-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed. RESULTS: Plasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median. Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses. CONCLUSION: In this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.

Bone marrow- or adipose-mesenchymal stromal cell secretome preserves myocardial transcriptome profile and ameliorates cardiac damage following ex vivo cold storage.

BACKGROUND: Heart transplantation, a life-saving approach for patients with end-stage heart disease, is limited by shortage of donor organs. While prolonged storage provides more organs, it increases the extent of ischemia. Therefore, we seek to understand molecular mechanisms underlying pathophysiological changes of donor hearts during prolonged storage. Additionally, considering mesenchymal stromal cell (MSC)-derived paracrine protection, we aim to test if MSC secretome preserves myocardial transcriptome profile and whether MSC secretome from a certain source provides the optimal protection in donor hearts during cold storage. METHODS AND RESULTS: Isolated mouse hearts were divided into: no cold storage (control), 6 h cold storage (6 h-I), 6 h-I + conditioned media from bone marrow MSCs (BM-MSC CM), and 6 h-I + adipose-MSC CM (Ad-MSC CM). Deep RNA sequencing analysis revealed that compared to control, 6 h-I led to 266 differentially expressed genes, many of which were implicated in modulating mitochondrial performance, oxidative stress response, myocardial function, and apoptosis. BM-MSC CM and Ad-MSC CM restored these gene expression towards control. They also improved 6 h-I-induced myocardial functional depression, reduced inflammatory cytokine production, decreased apoptosis, and reduced myocardial H2O2. However, neither MSC-exosomes nor exosome-depleted CM recapitulated MSC CM-ameliorated apoptosis and CM-improved mitochondrial preservation during cold ischemia. Knockdown of Per2 by specific siRNA abolished MSC CM-mediated these protective effects in cardiomyocytes following 6 h cold storage. CONCLUSIONS: Our results demonstrated that using MSC secretome (BM-MSCs and Ad-MSCs) during prolonged cold storage confers preservation of the normal transcriptional "fingerprint", and reduces donor heart damage. MSC-released soluble factors and exosomes may synergistically act for donor heart protection.

A Recombinant Dimethylarginine Dimethylaminohydrolase-1-Based Biotherapeutics to Pharmacologically Lower Asymmetric Dimethyl Arginine, thus Improving Postischemic Cardiac Function and Cardiomyocyte Mitochondrial Activity.

High serum levels of asymmetric dimethyl arginine (ADMA) are associated with cardiovascular disease and mortality. Pharmacological agents to specifically lower ADMA and their potential impact on cardiovascular complications are not known. In this study, we aimed to investigate the effect of specific lowering of ADMA on myocardial response to ischemia-reperfusion injury (I/R) and direct effects on cardiomyocyte function. Effects of recombinant dimethylarginine dimethylaminohydrolase (rDDAH)-1 on I/R injury were determined using isolated mouse heart preparation. Respiration capacity and mitochondrial reactive oxygen species (ROS) generation were determined on mouse cardiomyocytes. Our results show that lowering ADMA by rDDAH-1 treatment resulted in improved recovery of cardiac function and reduction in myocardial infarct size in mouse heart response to I/R injury (control 22.24 ±4.60% versus rDDAH-1 15.90 ±4.23%, P < 0.01). In mouse cardiomyocytes, rDDAH-1 treatment improved ADMA-induced dysregulation of respiration capacity and decreased mitochondrial ROS. Furthermore, in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes with impaired contractility under hypoxia and high ADMA, rDDAH-1 treatment improved recovery and beating frequency (P < 0.05). rDDAH-1 treatment selectively modified I/R-induced myocardial cytokine expression, resulting in reduction in proinflammatory cytokine IL-17A (P < 0.001) and increased expression of anti-inflammatory cytokines IL-10 and IL-13 (P < 0.01). Further in vitro studies showed that IL-17A was the predominant and common cytokine modulated by ADMA-DDAH pathway in heart, cardiomyocytes, and endothelial cells. These studies show that lowering ADMA by pharmacological treatment with rDDAH-1 reduced I/R injury, improved cardiac function, and ameliorated cardiomyocyte bioenergetics and beating activity. These effects may be attributable to ADMA lowering in cardiomyocytes and preservation of cardiomyocyte mitochondrial function. SIGNIFICANCE STATEMENT: The pathological role of asymmetric dimethyl arginine (ADMA) has been demonstrated by its association with cardiovascular disease and mortality. Currently, pharmacological drugs to specifically lower ADMA are not available. The present study provides the first evidence that lowering of ADMA by recombinant recombinant dimethylarginine dimethylaminohydrolase (rDDAH)-1 improved postischemic cardiac function and cardiomyocyte bioenergetics and beating activity. Our studies suggest that lowering of ADMA by pharmacologic treatment offers opportunity to develop new therapies for the treatment of cardiovascular and renal disease.

Annual report to the nation on the status of cancer, part 1: National cancer statistics.

BACKGROUND: The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States. METHODS: Data on new cancer diagnoses during 2001-2018 were obtained from the North American Association of Central Cancer Registries' Cancer in North America Incidence file, which is comprised of data from Centers for Disease Control and Prevention-funded and National Cancer Institute-funded, population-based cancer registry programs. Data on cancer deaths during 2001-2019 were obtained from the National Center for Health Statistics' National Vital Statistics System. Five-year average incidence and death rates along with trends for all cancers combined and for the leading cancer types are reported by sex, racial/ethnic group, and age. RESULTS: Overall cancer incidence rates were 497 per 100,000 among males (ranging from 306 among Asian/Pacific Islander males to 544 among Black males) and 431 per 100,000 among females (ranging from 309 among Asian/Pacific Islander females to 473 among American Indian/Alaska Native females) during 2014-2018. The trend during the corresponding period was stable among males and increased 0.2% on average per year among females, with differing trends by sex, racial/ethnic group, and cancer type. Among males, incidence rates increased for three cancers (including pancreas and kidney), were stable for seven cancers (including prostate), and decreased for eight (including lung and larynx) of the 18 most common cancers considered in this analysis. Among females, incidence rates increased for seven cancers (including melanoma, liver, and breast), were stable for four cancers (including uterus), and decreased for seven (including thyroid and ovary) of the 18 most common cancers. Overall cancer death rates decreased by 2.3% per year among males and by 1.9% per year among females during 2015-2019, with the sex-specific declining trend reflected in every major racial/ethnic group. During 2015-2019, death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, with the steepest declines (>4% per year) reported for lung cancer and melanoma. Five-year survival for adenocarcinoma and neuroendocrine pancreatic cancer improved between 2001 and 2018; however, overall incidence (2001-2018) and mortality (2001-2019) continued to increase for this site. Among children (younger than 15 years), recent trends were stable for incidence and decreased for mortality; and among, adolescents and young adults (aged 15-39 years), recent trends increased for incidence and declined for mortality. CONCLUSIONS: Cancer death rates continued to decline overall, for children, and for adolescents and young adults, and treatment advances have led to accelerated declines in death rates for several sites, such as lung and melanoma. The increases in incidence rates for several common cancers in part reflect changes in risk factors, screening test use, and diagnostic practice. Racial/ethnic differences exist in cancer incidence and mortality, highlighting the need to understand and address inequities. Population-based incidence and mortality data inform prevention, early detection, and treatment efforts to help reduce the cancer burden in the United States.

Cosmological milestones, conformal frameworks and quiescent cosmology.

To understand the nature of the birth of our Universe and its eventual demise is a driving force in theoretical physics and astronomy and, indeed, for humanity. A zoo of definitions has appeared in the literature to catalogue different types of cosmological milestones such as 'Big Bangs', 'Big Crunches', 'Big Rips', 'Sudden Singularities', 'Bounces' and 'Turnarounds'. Quiescent cosmology is the notion that the Universe commenced in a Big Bang that was highly regular and smooth, and evolved away from this initial isotropy and homogeneity due to gravitational attraction. The quiescent cosmology concept meshes well with Penrose's ideas regarding gravitational entropy and the clumping of matter, and the associated Weyl Curvature Hypothesis. Conformal frameworks, such as the Isotropic Past Singularity (IPS), have been devised to encapsulate initial and final states for the Universe which are in accordance with these programmes. These geometric definitions are independent of models, coordinates and the equation of state of the source of the gravitational field. Much of the research on cosmological milestones has been focussed on the FRW solutions, many of which possess initial singularities which are isotropic Big Bangs. We analyse here the relationship between cosmological milestones and conformal frameworks for these solutions. We establish the general properties of FRW models which admit these conformal frameworks, including whether they satisfy various energy conditions, and are therefore physically reasonable. These results inform future development of the quiescent cosmology program. This article is part of the theme issue 'The future of mathematical cosmology, Volume 1'.

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of navitoclax.

The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax-d8, was achieved with a Waters Acquity UPLC BEH C18 column using isocratic flow over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5-5,000 ng/ml and proved to be accurate (89.5-104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at -70°C was at least 34 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose.

The Families First Program to Prevent Child Abuse: Results of a Cluster Randomized Controlled Trial in West Java, Indonesia.

The Families First parenting program is a 10-week paraprofessional-administered adaptation of the Positive Discipline in Everyday Parenting program for West Java, Indonesia. It has not been tested in a randomized controlled trial. The objective was to evaluate the effects of Families First on physical and emotional punishment. We conducted a cluster randomized controlled trial and randomly assigned 20 rural and urban villages in West Java, Indonesia, to intervention or waitlist. Caregivers of children aged 0-7 years in intervention villages received Families First. Between 2017 and 2018, measurements were taken before randomization, immediately post-intervention, and 6 months post-intervention. Primary outcome was presence versus absence of caregiver-reported physical or emotional punishment immediately post-intervention. Intention-to-treat regression models accounted for clustering within villages and were run to compare between groups. Participants and study personnel could not be blinded. There were 374 caregivers in the 10 intervention villages and 362 in the 10 waitlist villages included in the trial and in outcome analyses. The intervention did not result in a lower proportion of intervention families using punishment immediately post-intervention (odds ratio [OR] for physical or emotional punishment immediately post intervention = 1.20 (95% CI 0.79-1.82). There were no significant differences for positive and involved parenting, setting limits, and opinion on discipline, but caregivers in the intervention group had significantly lower odds of using positive discipline (OR = 0.65 (95% CI 0.53-0.80). Families First did not prevent punishment in a setting with low levels of reported punishment but should be tested in a setting with higher levels or among people selected for risk or presence.

Sex as Biological Variable in Cardiac Mitochondrial Bioenergetic Responses to Acute Stress.

Cardiac dysfunction/damage following trauma, shock, sepsis, and ischemia impacts clinical outcomes. Acute inflammation and oxidative stress triggered by these injuries impair mitochondria, which are critical to maintaining cardiac function. Despite sex dimorphisms in consequences of these injuries, it is unclear whether mitochondrial bioenergetic responses to inflammation/oxidative stress are sex-dependent. We hypothesized that sex disparity in mitochondrial bioenergetics following TNFα or H2O2 exposure is responsible for reported sex differences in cardiac damage/dysfunction. Methods and Results: Cardiomyocytes isolated from age-matched adult male and female mice were subjected to 1 h TNFα or H2O2 challenge, followed by detection of mitochondrial respiration capacity using the Seahorse XF96 Cell Mito Stress Test. Mitochondrial membrane potential (ΔΨm) was analyzed using JC-1 in TNFα-challenged cardiomyocytes. We found that cardiomyocytes isolated from female mice displayed a better mitochondrial bioenergetic response to TNFα or H2O2 than those isolated from male mice did. TNFα decreased ΔΨm in cardiomyocytes isolated from males but not from females. 17ß-estradiol (E2) treatment improved mitochondrial metabolic function in cardiomyocytes from male mice subjected to TNFα or H2O2 treatment. Conclusions: Cardiomyocyte mitochondria from female mice were more resistant to acute stress than those from males. The female sex hormone E2 treatment protected cardiac mitochondria against acute inflammatory and oxidative stress.

Induced abortions in women with systemic lupus erythematosus.

OBJECTIVES: To determine the rates of induced abortions in women with systemic lupus erythematosus (SLE) compared to women from the general population and assess disease-related predictors of induced abortion in women with SLE. METHODS: We identified women with SLE (15-45 years) and determined the number of induced abortions, using Quebec's administrative databases. We calculated the standardized incidence ratio (SIR) using general population rates. We also performed a nested-case control analysis to investigate predictors of induced abortions in SLE women (such as teratogenic immunosuppressive and corticosteroid exposures). RESULTS: Among 2508 women with SLE, we observed 293 induced abortions [incidence rate of 17.1 induced abortions per 1000 person-years (95% CI 15.2, 19.2)]. There was no clear difference in the number of induced abortions among women with SLE versus women from the general population (SIR 1.10; 95% CI 0.98, 1.24). In the multivariable analysis, we did not observe higher rates of induced abortions among women exposed to teratogenic immunosuppressives [rate ratio (RR) 0.37; 95% CI 0.13, 1.07] or using corticosteroids (RR 0.67; 95% CI 0.39, 1.16). CONCLUSION: Our findings suggest that women with SLE have a similar rate of induced abortions as compared to the general population. This raises some concerns as unplanned pregnancies in SLE women can lead to adverse maternal and fetal outcomes. Our results should prompt further research on family planning counselling in women with SLE.

Immunotherapy for small cell lung cancer: established applications and novel approaches.

Small cell lung cancer (SCLC) is a devastating disease that has a case fatality rate of more than 90% despite best available treatments. As a result, patients with SCLC are in critical need of improved therapeutic approaches. Immunotherapies, in particular immune checkpoint inhibitors (ICIs), have transformed the treatment of many cancers and are of great interest in SCLC. In recent years, the addition of anti-programmed death ligand 1 (PD-L1) inhibitors to frontline platinum-based chemotherapy in extensive-stage SCLC has improved survival, and combination chemoimmunotherapy is now approved as the standard of care. ICIs are also under investigation in other settings, including as consolidation therapy in limited-stage SCLC following chemoradiation and in combination with chemoradiation. PD-L1 expression and tumor mutational burden are not reliably associated with ICI benefit in SCLC, and predictive biomarkers of ICI response in SCLC are actively sought. Novel immunotherapeutic approaches are under investigation in SCLC. Rational targets and combinations, which stem from investigations of SCLC biology and the immune tumor microenvironment, include combinations with inhibitors of TIGIT or LAG3; targeting alternative signaling pathways, such as DNA damage repair; and co-targeting SCLC-specific tumor antigens, such as fucosyl-GM1 and DLL3. This review summarizes approaches to immunotherapy in SCLC, including current evidence and approvals, as well as key questions and future directions.

The Pandemic's Toll-A Case for Clinician Support.

Healthcare providers perform lifesaving work in unusually stressful work environments due to the challenges and related risks of battling the unprecedented COVID-19 pandemic. The potential personal and professional toll is substantial. This article describes how one healthcare facility benefited from existing peer support resources to address workforce well-being, ensuring that resources were available to support workforce resilience throughout the protracted COVID response.

Annual report to the nation on the status of cancer, part II: Progress toward Healthy People 2020 objectives for 4 common cancers.

BACKGROUND: The Centers for Disease Control and Prevention, the American Cancer Society, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States and to address a special topic of interest. Part I of this report focuses on national cancer statistics, and part 2 characterizes progress in achieving select Healthy People 2020 cancer objectives. METHODS: For this report, the authors selected objectives-including death rates, cancer screening, and major risk factors-related to 4 common cancers (lung, colorectal, female breast, and prostate). Baseline values, recent values, and the percentage change from baseline to recent values were examined overall and by select sociodemographic characteristics. Data from national surveillance systems were obtained from the Healthy People 2020 website. RESULTS: Targets for death rates were met overall and in most sociodemographic groups, but not among males, blacks, or individuals in rural areas, although these groups did experience larger decreases in rates compared with other groups. During 2007 through 2017, cancer death rates decreased 15% overall, ranging from -4% (rural) to -22% (metropolitan). Targets for breast and colorectal cancer screening were not yet met overall or in any sociodemographic groups except those with the highest educational attainment, whereas lung cancer screening was generally low (<10%). Targets were not yet met overall for cigarette smoking, recent smoking cessation, excessive alcohol use, or obesity but were met for secondhand smoke exposure and physical activity. Some sociodemographic groups did not meet targets or had less improvement than others toward reaching objectives. CONCLUSIONS: Monitoring trends in cancer risk factors, screening test use, and mortality can help assess the progress made toward decreasing the cancer burden in the United States. Although many interventions to reduce cancer risk factors and promote healthy behaviors are proven to work, they may not be equitably applied or work well in every community. Implementing cancer prevention and control interventions that are sustainable, focused, and culturally appropriate may boost success in communities with the greatest need, ensuring that all Americans can access a path to long, healthy, cancer-free lives.

Annual report to the nation on the status of cancer, part I: National cancer statistics.

BACKGROUND: The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States. METHODS: Data on new cancer diagnoses during 2001 through 2016 were obtained from the Centers for Disease Control and Prevention-funded and National Cancer Institute-funded population-based cancer registry programs and compiled by the North American Association of Central Cancer Registries. Data on cancer deaths during 2001 through 2017 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in incidence and death rates for all cancers combined and for the leading cancer types by sex, racial/ethnic group, and age were estimated by joinpoint analysis and characterized by the average annual percent change during the most recent 5 years (2012-2016 for incidence and 2013-2017 for mortality). RESULTS: Overall, cancer incidence rates decreased 0.6% on average per year during 2012 through 2016, but trends differed by sex, racial/ethnic group, and cancer type. Among males, cancer incidence rates were stable overall and among non-Hispanic white males but decreased in other racial/ethnic groups; rates increased for 5 of the 17 most common cancers, were stable for 7 cancers (including prostate), and decreased for 5 cancers (including lung and bronchus [lung] and colorectal). Among females, cancer incidence rates increased during 2012 to 2016 in all racial/ethnic groups, increasing on average 0.2% per year; rates increased for 8 of the 18 most common cancers (including breast), were stable for 6 cancers (including colorectal), and decreased for 4 cancers (including lung). Overall, cancer death rates decreased 1.5% on average per year during 2013 to 2017, decreasing 1.8% per year among males and 1.4% per year among females. During 2013 to 2017, cancer death rates decreased for all cancers combined among both males and females in each racial/ethnic group, for 11 of the 19 most common cancers among males (including lung and colorectal), and for 14 of the 20 most common cancers among females (including lung, colorectal, and breast). The largest declines in death rates were observed for melanoma of the skin (decreasing 6.1% per year among males and 6.3% among females) and lung (decreasing 4.8% per year among males and 3.7% among females). Among children younger than 15 years, cancer incidence rates increased an average of 0.8% per year during 2012 to 2016, and cancer death rates decreased an average of 1.4% per year during 2013 to 2017. Among adolescents and young adults aged 15 to 39 years, cancer incidence rates increased an average of 0.9% per year during 2012 to 2016, and cancer death rates decreased an average of 1.0% per year during 2013 to 2017. CONCLUSIONS: Although overall cancer death rates continue to decline, incidence rates are leveling off among males and are increasing slightly among females. These trends reflect population changes in cancer risk factors, screening test use, diagnostic practices, and treatment advances. Many cancers can be prevented or treated effectively if they are found early. Population-based cancer incidence and mortality data can be used to inform efforts to decrease the cancer burden in the United States and regularly monitor progress toward goals.

Relationships between cognition, function, and quality of life among HIV+ Canadian men.

OBJECTIVE: To estimate the extent to which HIV-related variables, cognition, and other brain health factors interrelate with other HIV-associated symptoms to influence function, health perception, and QOL in older HIV+ men in Canada. DESIGN: Cross-sectional structural equation modelling (SEM) of data from the inaugural visit to the Positive Brain Health Now Cohort. SETTING: HIV clinics at 5 Canadian sites. SUBJECTS: 707 men, age ≥ 35 years, HIV+ for at least one year, without clinically diagnosed dementia. MAIN OUTCOME MEASURES: Five latent and 21 observed variables from the World Health Organization's biopsychosocial model for functioning and disability and the Wilson-Cleary Model were analysed. SEM was used to link disease factors to symptoms, impairments, function, health perception, and QOL with a focus on cognition. RESULTS: QOL was explained directly by depression, social role, health perception, social support, and quality of the environment. Measured cognitive performance had direct effects on activity/function and indirect effects on participation, HP and QOL, acting through self-reported cognitive difficulties and meaningful activities. CONCLUSION: The biopsychosocial model showed good fit, with RMSEA < 0.05. This is the first time the full model has been tested in HIV. All of the domains included in the model are theoretically amenable to intervention and many have evidence-based interventions that could be harnessed to improve QOL.

Spontaneous renal fornix rupture in pregnancy and the post partum period: a systematic review of outcomes and management.

BACKGROUND: Spontaneous renal fornix rupture (SRFR) causing urinoma is an uncommon but serious condition in pregnancy. Limited information is available to describe the natural history and outcomes to guide appropriate treatment. The aim of this study was to determine the natural history and outcomes of SRFR to determine appropriate management recommendations. METHODS: A systematic review of literature databases was performed, using the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) checklist from 1950 - April 2020. Inclusion criteria included any urinary extravasation from the kidney or ureter during pregnancy, or in the 8 weeks following delivery, confirmed via imaging or surgery. Haematomas and non-confirmed cases were excluded. RESULTS: A total of 1579 records were originally identified, of which 39 case reports were appropriate for inclusion. SRFR was most commonly reported during the first pregnancy (72%), 19/30 during the third trimester and 9 in the post-natal period. All patients presented with pain, with haematuria positive on urine dipstick in only 36% of 26 reported cases. Ultrasound was the most frequently used imaging modality, resulting in a diagnosis in 42% of cases. All cases reported on treatment procedures including ureteric stents (46%), percutaneous drain (15%), conservative management (15%), nephrostomy (13%) and ureteral catherization (10%). Long term urological outcomes were positive, however women suffering SRFR were significantly more likely to undergo pre-term labour. CONCLUSION: While selected cases may be successfully managed conservatively, urinary diversion, through ureteric stents, should be considered the management of choice in these individuals. Clinicians should be mindful of an increased risk of premature delivery and its' associated negative fetal outcomes.

An Evaluation of Nurses' Perception and Confidence After Implementing a Workplace Aggression and Violence Prevention Training Program.

Workplace violence is highly prevalent for nurses, often going unreported. Regrettably, the very patients and visitors being cared for often perpetrate the majority of violence. This article's purpose is to describe how an institution implemented a workplace violence prevention training program designed to increase nurses' perception and confidence with aggressive and violent events. Evaluation of this quality improvement program posttraining was positive, suggesting this approach may influence nurses' abilities to prevent and manage these events.

Pathological Responses of Cardiac Mitochondria to Burn Trauma.

Despite advances in treatment and care, burn trauma remains the fourth most common type of traumatic injury. Burn-induced cardiac failure is a key factor for patient mortality, especially during the initial post-burn period (the first 24 to 48 h). Mitochondria, among the most important subcellular organelles in cardiomyocytes, are a central player in determining the severity of myocardial damage. Defects in mitochondrial function and structure are involved in pathogenesis of numerous myocardial injuries and cardiovascular diseases. In this article, we comprehensively review the current findings on cardiac mitochondrial pathological changes and summarize burn-impaired mitochondrial respiration capacity and energy supply, induced mitochondrial oxidative stress, and increased cell death. The molecular mechanisms underlying these alterations are discussed, along with the possible influence of other biological variables. We hope this review will provide useful information to explore potential therapeutic approaches that target mitochondria for cardiac protection following burn injury.

A contemporary, nationwide analysis of surgery and radiotherapy treatment for prostate cancer.

OBJECTIVE: To characterize national clinical practice trends in the treatment of prostate cancer (PCa) in Australia. PATIENTS AND METHODS: Population-level data were extracted from existing Medicare Benefits Schedule data for radical prostatectomy (RP) and brachytherapy (2002-2016), as well as external beam radiotherapy (EBRT; 2012-2016). Treatment rates were calculated relative to whole and PCa populations among privately treated patients. Overall age-related and geographical trends were analysed. RESULTS: The use of RP and low-dose-rate (LDR) brachytherapy increased between 2002 and 2009, but subsequently decreased to 124 and 6.9 per 100 000 men, respectively, in 2016. More dramatic decreases were observed for men aged <65 years. From 2012, rates of RP (15% drop) and LDR brachytherapy (58% drop) decreased, while the use of EBRT remained steady, falling by 5% to 42 per 100 000 men in 2016. Overall treatment increased in the age group 75-84 years, with the rate of RP increasing by 108%. CONCLUSION: National claims data indicate there has been a reduction in PCa treatment since 2009, which is mostly attributable to a reduction in the treatment of younger patients and reduced use of brachytherapy. RP is most commonly used and its use is rising in men aged >65 years.