Multiple myeloma incidence, mortality, and prevalence estimates and projections, Australia, 1982-2043: a statistical modelling study.

OBJECTIVES: To examine changes in multiple myeloma incidence and mortality rates during 1982-2018, and to estimate its incidence, mortality, and prevalence for 2019-2043. STUDY DESIGN: Population-based statistical modelling study; analysis of and projections based on Australian Institute of Health and Welfare multiple myeloma incidence, mortality, and survival data. SETTING: Australia, 1982-2018 (historical data) and projections to 2043. MAIN OUTCOME MEASURES: Changes in multiple myeloma incidence and mortality rates, 1982-2018, determined by joinpoint regression analysis (age-standardised to 2021 Australian population); projection of rates to 2043 based on age-period-cohort models; estimated 5- and 30-year prevalence of multiple myeloma (modified counting method). RESULTS: The incidence of multiple myeloma increased during 1982-2018 (eg, annual percentage change [APC], 2006-2018, 1.9%; 95% confidence interval [CI], 1.7-2.2%), but the mortality rate declined during 1990-2018 (APC, -0.4%; 95% CI, -0.5% to -0.2%). The age-standardised incidence rate was projected to increase by 14.9% during 2018-2043, from 8.7 in 2018 to 10.0 (95% CI, 9.4-10.7) new cases per 100 000 population in 2043; the mortality rate was projected to decline by 27.5%, from 4.0 to 2.9 (95% CI, 2.6-3.3) deaths per 100 000 population. The annual number of people newly diagnosed with multiple myeloma was estimated to increase by 89.2%, from 2120 in 2018 to 4012 in 2043; the number of deaths from multiple myeloma was projected to increase by 31.7%, from 979 to 1289. The number of people living with multiple myeloma up to 30 years after initial diagnosis was projected to increase by 163%, from 10 288 in 2018 to 27 093 in 2043, including 13 019 people (48.1%) diagnosed during the preceding five years. CONCLUSION: Although the decline in the mortality rate was projected to continue, the projected increases in the incidence and prevalence of multiple myeloma in Australia over the next 25 years indicate that investment in prevention and early detection research, and planning for prolonged treatment and care, are needed.

Multiple myeloma survival in New South Wales, Australia, by treatment era to 2020.

OBJECTIVE: Australia has relatively high multiple myeloma (MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries; however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales (NSW), Australia. METHODS: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date (1985-1995, chemotherapy only; 1996-2007, autologous stem cell transplantation; and 2008-2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis. RESULTS: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year (1985-2020) study period (31.0% in 1985-1995; 41.9% in 1996-2007; and 56.1% in 2008-2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985-1995 to 68.5% in 2008-2015. Improvements for those > 70 years of age were less pronounced between 1985-1995 and 1996-2007; however, significant improvements were observed for those diagnosed in 2008-2015. Similar overall and age-specific patterns were observed for cause-specific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival (P < 0.0001). CONCLUSIONS: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.

Long-term Outcome of Cryoballoon Ablation in Korean Patients With Atrial Fibrillation: Real-world Experience From the Cryo Global Registry.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF), the most common atrial arrhythmia (AA), is an increasing healthcare burden in Korea. The objective of this sub-analysis of the Cryo Global Registry was to evaluate long-term efficacy, symptom burden, quality of life (QoL), and healthcare utilization outcomes and factors associated with AA recurrence in Korean patients treated with cryoballoon ablation (CBA). METHODS: Patients were treated and followed up according to local standard-of-care in 3 Korean hospitals. Kaplan-Meier estimates were used in analyzing (1) efficacy defined as freedom from ≥30 second recurrence of AA at 24 months, (2) healthcare utilization, and (3) predictors of 24-month AA recurrence. Patient-reported QoL (using European Quality of Life-5 Dimensions-3 Levels) and predefined AF-related symptoms were assessed at baseline and 24-month follow-up. RESULTS: Efficacy was 71.9% in paroxysmal AF (PAF) and 49.3% in persistent AF (PsAF) patients (p<0.01). A larger left atrial diameter (LAD), an increased time from AF diagnosis to CBA, and PsAF were independent predictors of AA recurrence. The percentage of patients with no AF symptoms significantly increased from baseline (24.5%) to 24-month (89.5%) follow-up (p<0.01). Improvement in QoL from baseline to 24 months was not statistically different between AF cohorts. PAF patients experienced greater freedom from repeat ablations (93.9% vs. 81.4%) and cardiovascular hospitalizations (91.3% vs. 72.5%, p<0.001 for both). CONCLUSIONS: In alignment with global outcomes, CBA is an effective treatment for AF in the Korean population, with patients possessing a large LAD and not receiving ablation soon after diagnosis being the most at risk for AA recurrence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02752737.

Cardiogenic Shock and Utilization of Mechanical Circulatory Support in Pregnancy.

Maternal mortality rates are rising in the United States, a trend which is in contrast to that seen in other high-income nations. Cardiovascular disease and hypertensive disorders of pregnancy are consistently the leading causes of maternal mortality both in the United States and globally, accounting for about one-quarter to one-third of maternal and peripartum deaths. A large proportion of cardiovascular morbidity and mortality stems from acquired disease in the context of cardiovascular risk factors, which include obesity, pre-existing diabetes and hypertension, and inequities in care from maternal care deserts and structural racism. Patients may also become pregnant with preexisting structural heart disease, or acquire disease throughout pregnancy (ex: spontaneous coronary artery dissection, peripartum cardiomyopathy), and be at higher risk of pregnancy-related cardiovascular complications. While risk-stratification tools including the modified World Health Organization (mWHO) classification, Cardiac Disease in Pregnancy (CARPREG II) and Zwangerschap bij Aangeboren HARtAfwijking/Pregnancy in Women with Congenital Heart Disease (ZAHARA) have been designed to help physicians identify patients at increased risk for adverse pregnancy outcomes and who may therefore benefit from referral to a tertiary care center, the limitation of these scores is their predominant focus on patients with known preexisting heart disease. As such, identifying patients at risk for pregnancy complications presents a significant challenge, and it is often patients with high-risk cardiovascular substrates prior to or during pregnancy who are at a highest risk for adverse pregnancy outcomes including cardiogenic shock.

Unannotated Open Reading Frame in Saccharomyces cerevisiae Encodes Protein Localizing to the Endoplasmic Reticulum.

There are thousands of unannotated translated open reading frames (ORFs) in the Saccharomyces cerevisiae genome. Previous investigation into one such unannotated ORF, which was systemically labeled YGR016C-A based on its genomic coordinates, showed that replacing the ORF's ATG start codon with AAG led to a change in cellular fitness under different stress conditions (Wacholder et al., 2023). This suggested translation of YGR016C-A plays a role in cellular fitness. Here, we investigate Ygr016c-a's subcellular localization to gain insight into its cellular function. Computational prediction tools, co-expression analysis and fluorescence microscopy suggest that the Ygr016c-a protein localizes to the endoplasmic reticulum.

Compensatory coping and depression in women with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Women with genitourinary pain, a hallmark symptom of interstitial cystitis/bladder pain syndrome (IC/BPS), are at a two- to four-fold risk for depression as compared to women without genitourinary pain. Despite the pervasive impact of IC/BPS on psychological health, there is a paucity of empirical research on understanding the relation between IC/BPS and psychological distress. It has been previously reported that women with overactive bladder use increased compensatory coping and these behaviors are associated with heightened anxiety and stress. However, it is unknown whether a similar pattern emerges in IC/BPS populations, as ICBPS and OAB share many similar urinary symptoms. The current study examined the relationship between compensatory coping behaviors and symptoms of psychological distress in a sample of women with IC/BPS to inform understanding of risk and potential mechanisms for intervention. METHOD: This was a secondary analysis of an observational cohort of women with bladder symptoms. Fifty-five adult women with IC/BPS completed validated assessments of genitourinary symptoms, emotional distress, and bladder coping behaviors. Five compensatory coping behaviors were summed to create a total Bladder Coping Score. Linear regression examined associations between individual coping behaviors, total compensatory coping scores, and other risk variables. RESULTS: Most (93%) participants reported use of at least one compensatory coping behavior. Age, education level, history of vaginal birth, and symptom severity were all associated with greater compensatory coping scores, and anxiety was not. Beyond the influence of symptom severity, higher levels of depression were significantly associated with higher compensatory coping scores. DISCUSSION: Greater compensatory coping was associated with increased depression but not anxiety, suggesting different profiles of coping and psychological distress may exist among different types of bladder dysfunction.

Cryoballoon Catheter Ablation in Korean Patients With Paroxysmal and Persistent Atrial Fibrillation: One Year Outcome From the Cryo Global Registry.

BACKGROUND AND OBJECTIVES: Cryoballoon catheter ablation for the treatment of patients with symptomatic atrial fibrillation (AF) has been adopted globally, but there are limited multicenter reports of 12-month outcomes in the Korean patient population. This analysis evaluated the clinical performance and safety of cryoballoon ablation (CBA) according to standard-of-care practices in Korea. METHODS: This evaluation of Korean patients with AF was conducted within the larger Cryo Global Registry, which is a prospective, multicenter, post-market registry. Freedom from a ≥30-second recurrence of atrial arrhythmias (after a 90-day blanking period until 12 months) and procedural safety were examined in subjects treated with CBA at 3 Korean centers. RESULTS: Overall, 299 patients with AF (60±11 years old, 24.7% female, 50.5% paroxysmal AF) underwent CBA using the Arctic Front Advance cryoballoon. Of those, 298 were followed-up for at least 12 months. Mean procedure-, left atrial dwell- and fluoroscopy time was 76±21 minutes, 56±23 minutes, and 27±23 minutes, respectively. Freedom from AF recurrence at 12 months was 83.9% (95% confidence interval [CI], 76.9-88.9%) in the paroxysmal and 61.6% (95% CI, 53.1-69.0%) in the persistent AF cohort. Rhythm monitoring was performed on average 4.7±1.4 times during the follow-up period. Serious device- or procedure-related adverse events occurred in 2 patients (0.7%). The 12-month Kaplan-Meier estimate of freedom from repeat ablation and cardiovascular-related hospitalization was 93.8% (95% CI, 90.4-96.1%) and 89.7% (95% CI, 85.6-92.7%), respectively. CONCLUSIONS: CBA is an efficient, effective, and safe procedure for the treatment of AF patients when used according to real-world practices in Korea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02752737.

The utility of a safety climate scale among workers with a work-related permanent impairment who have returned to work.

BACKGROUND: Safety climate (SC) is a robust leading indicator of occupational safety outcomes. There is, however, limited research on SC among workers who have returned to work with a work-related permanent impairment. OBJECTIVE: This study examined three propositions: (1) a two-level model of SC (group-level and organization-level SC) will provide the best fit to the data; (2) antecedent factors such as safety training, job demands, supervisor support, coworker support, and decision latitude will predict SC; and (3) previously reported associations between SC and outcomes such as reinjury, work-family conflict, job performance, and job security will be observed. METHOD: A representative cross-sectional survey gathered information about experiences during the first year of work reintegration. About one year after claim closure, 599 interviews with workers were conducted (53.8% response rate). Confirmatory factor analyses were conducted to test the factor structure of the SC construct. Further, researchers used correlation analyses to examine the criterion-related validity. RESULTS: Consistent with general worker populations, our findings suggest the following: (1) the two-factor structure of SC outperformed the single-factor structure in our population of workers with a permanent impairment; (2) correlations demonstrate that workplace safety training, decision latitude, supervisor support, coworker support, and job demands could predict SC; and (3) SC may positively impact reinjury risk, work-family conflict, and may increase job performance and job security. CONCLUSIONS: Our study validated a two-factor SC scale among workers with a history of disabling workplace injury or permanent impairment who have returned to work. Practical applications of this scale will equip organizations with the necessary data to improve working conditions for this population.

Acute Coronary Syndrome in Pregnancy and the Post-Partum Period.

Cardiovascular disease is the leading cause of maternal mortality in the United States. Acute coronary syndrome (ACS) is more common in pregnant women than in non-pregnant controls and contributes to the burden of maternal mortality. This review highlights numerous etiologies of chest discomfort during pregnancy, as well as risk factors and causes of ACS during pregnancy. It focuses on the evaluation and management of ACS during pregnancy and the post-partum period, including considerations when deciding between invasive and non-invasive ischemic evaluations. It also focuses specifically on the management of post-myocardial infarction complications, including shock, and outlines the role of mechanical circulatory support, including veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Finally, it offers additional recommendations for navigating delivery in women who experienced pregnancy-associated myocardial infarction and considerations for the post-partum patient who develops ACS.

A Comparison of High Drug Concentrations in Impaired Driving and Postmortem Casework in Harris County, TX.

Drug-impaired driving is a growing public safety issue. Addressing impairment due to drugs other than ethanol can be challenging for forensic toxicologists as many factors need to be considered including the type of drug(s), drug-drug interaction, the dose(s) and the individual's physiological condition and drug use history. Interpretation of blood drug test results is additionally difficult as drug concentrations in impaired driving cases may overlap levels typically viewed as toxic. This study compares blood concentrations of drugs in impaired driving cases to those in postmortem cases in Houston, TX, from 2014 to 2020. Blood drug concentrations from driving while intoxicated (DWI) or driving under the influence of drugs (DUID) cases submitted to Houston Forensic Science Center (HFSC) and Harris County Institute of Forensic Sciences (HCIFS) were compared to postmortem blood test results from HCIFS. Eight DWI/DUID cases had drugs that exceeded impaired driving concentrations reported in the literature. These drugs included fentanyl (220 ng/mL), oxycodone (680 ng/mL), hydrocodone (310 and 490 ng/mL), clonazepam (330 ng/mL), methamphetamine (3,500 and 7,100 ng/mL) and tetrahydrocannabinol (THC) (160 ng/mL). For oxycodone and hydrocodone, the presented DWI/DUID cases exceeded 91% and 96% of postmortem concentrations, respectively. The 7,100 ng/mL methamphetamine DWI/DUID result was greater than 98% of postmortem cases. The presented DWI/DUID concentrations were higher than all but one postmortem case for clonazepam and higher than all postmortem cases for THC. This study demonstrates that extremely high drug concentrations in DWI/DUID casework blur the line between therapeutic/recreational and toxic concentrations.

Something new and something blue: Responses to novelty in a rodent model of depression and epilepsy comorbidity.

A bidirectional comorbidity exists between depression and epilepsy such that patients with epilepsy are at higher risk for developing depression, and vice versa. Each of these conditions individually can be complicated by behavioral effects that worsen quality of life, but less is known about these interactions within the comorbidity of depression and epilepsy. The SwLo rat has been selectively bred for depression-relevant behaviors and exhibits enhanced limbic seizure susceptibility. This study sought to characterize the effects of novelty and stress on the SwLo rodent model of this comorbidity. It was hypothesized that SwLo rats would exhibit altered responses to novelty, reflected in hyperactivity-, anxiety-, sensation seeking-, and/or compulsive behaviors, and that this would be exacerbated with stress. Compared to the SwHi rat (their depression- and epilepsy-resistant counterparts), SwLo rats showed increased entries in all areas of the Open Field Test and spent significantly more time in the light compartment of the Light-Dark Box. SwLo rats also had a significantly higher number of rearing behaviors in the inner squares of the Open Field Test, the closed arms of the Elevated Plus Maze, and both areas of the Light-Dark Box. They demonstrated increased Nestlet shredding but showed no difference in a marble burying task or in latency to consume food in a novelty suppressed feeding task. Interestingly, restraint stress showed little effect on these behaviors, despite increasing corticosterone levels. Combined, these results suggest an increase in exploratory sensation seeking and hypervigilant information-gathering behaviors in the SwLo rat that are not dependent on corticosterone levels. This shows the utility of this model for studying behavioral effects of comorbid depression and epilepsy and allows for their use in identifying underlying mechanisms or screening treatment strategies for this complex comorbidity.

Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women.

Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman's reproductive history may influence or reveal short- and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) - a novel clinico-pathological entity with heterogeneous clinical presentations.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel entity that emerged in March 2021 following reports of unusual thrombosis after ChAdOx1 nCoV-19, (AstraZeneca) vaccination. Following the recognition of this syndrome, multiple consensus guidelines have been released to risk stratify patients presenting with possible symptoms after ChAdOx1 nCoV-19 vaccination. All guidelines rapidly identify VITT in patients with the complete triad of thrombocytopenia, thrombosis and elevated D-dimers after ChAdOx1 nCoV-19 vaccination. However, with earlier recognition of the associated symptoms, the clinical manifestations are likely to be more heterogeneous and represent an evolving spectrum of disease. In this setting, current guidelines may lack the sensitivity to detect early cases of VITT and risk missed or delayed diagnoses. The broad clinical phenotype and challenges associated with diagnosis of VITT are highlighted in our present case series of four patients with confirmed VITT. Dependent on the guidance used, each patient could have been classified as a low probability of VITT at presentation. The present study highlights the issues associated with the recognition of VITT, the limitations of current guidance and the need for heightened clinical vigilance as our understanding of the pathophysiology of this novel condition evolves.

Azygos Continuation of the Inferior Vena Cava: Potential for Misdiagnosis as Lung Neoplasm.

BACKGROUND: The azygos venous system is an accessory venous pathway supplying an important collateral circulation between the superior and inferior vena cava (IVC). CASE SUMMARY: We report a case of complicated community-acquired pneumonia with interruption of the IVC with azygos continuation that was misdiagnosed as lung neoplasm. DISCUSSION: The aim of this case report is to emphasize the importance of recognizing an enlarged azygos vein at the confluence with the superior vena cava and in the retrocrural space to avoid misdiagnosis as a right-sided para-tracheal mass. The angiographic features and clinical importance of this condition are discussed. LEARNING POINTS: An enlarged azygos vein at the confluence with the superior vena cava and in the retrocrural space can be misdiagnosed as a right-sided para-tracheal mass/neoplasm or retrocrural adenopathy.Biopsy is the most important tool to confirm the diagnosis of malignancy but could be catastrophic in this situation.Re-imaging after treatment for infection and pneumonia could potentially avoid this error.

Delivering Coordinated Cardio-Obstetric Care from Preconception through Postpartum.

Coordinated preconception through postpartum cardio-obstetrics care is necessary to optimize both maternal and fetal health. Maternal mortality in the United States is increasing, largely driven by increasing cardiovascular (CV) disease burden during pregnancy and needs to be addressed emergently. Both for women with congenital and acquired heart disease, CV complications during pregnancy are associated with increased future risk of CV disease. Comprehensive cardio-obstetrics care is a powerful way of ensuring that women's CV risks before and during pregnancy are appropriately identified and treated and that they remain engaged in CV care long term to prevent future CV complications.

Assessment of anxiety in children and adolescents: A comparative study on the validity and reliability of the Spence Children's Anxiety Scale in children and adolescents with anxiety and Autism Spectrum Disorder.

OBJECTIVE: The present study assessed the utility of the Spence Children's Anxiety Scale - Parent Form (SCAS-P) across parents of children with (i) anxiety and (ii) Autism Spectrum Disorder (ASD). METHOD: Parents of children aged 7-18 years with anxiety or ASD completed the SCAS-P. Multiple indicator multiple cause (MIMIC) structural equation modelling was utilized to analyse the data. RESULTS: Analysis revealed different factor structures between the Anxious and ASD groups and evidence for measurement variance across groups in some parts of the SCAS-P. CONCLUSION: Results on the SCAS-P in children with ASD need to be interpreted with caution. Some SCAS-P items cannot be interpreted in the same way in an ASD population compared to neurotypical children with anxiety.