Why is a small sample size not enough?

BACKGROUND: Clinical studies are often limited by resources available, which results in constraints on sample size. We use simulated data to illustrate study implications when the sample size is too small. METHODS AND RESULTS: Using 2 theoretical populations each with N = 1000, we randomly sample 10 from each population and conduct a statistical comparison, to help make a conclusion about whether the 2 populations are different. This exercise is repeated for a total of 4 studies: 2 concluded that the 2 populations are statistically significantly different, while 2 showed no statistically significant difference. CONCLUSIONS: Our simulated examples demonstrate that sample sizes play important roles in clinical research. The results and conclusions, in terms of estimates of means, medians, Pearson correlations, chi-square test, and P values, are unreliable with small samples.

Differences in Rural Versus Urban Patients With Prostate Cancer in Diagnosis and Treatment: An Analysis of a Population-Based Cohort.

PURPOSE: Patients living in rural communities have greater barriers to cancer care and poorer outcomes. We hypothesized that rural patients with prostate cancer have less access and receive different treatments compared with urban patients. METHODS: We used a population-based prospective cohort, the North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study, to compare differences in prostate cancer diagnosis, access to care, and treatment in patients by geographic residence. The 2013 rural-urban continuum code (RUCC) was used to determine urban (RUCC 1-3) versus rural (RUCC 4-9) location of residence. RESULTS: Patients with rural residence comprised 25% of the cohort (364 of 1,444); they were less likely to be White race and had lower income and educational attainment. Rural patients were more likely to have <12 cores on biopsy (47.1% v 35.7%; P < .001) and less likely (40.8% v 47.6%; P = .04) to receive multidisciplinary consultation. We observed significant differences in treatment between urban and rural patients, including rural patients receiving less active surveillance or observation (22.6% v 28.7%), especially in low-risk cancer (33.2% v 40.7%). On multivariable analysis that adjusted for patient and diagnostic factors, rural residence was associated with less use of active surveillance or observation over radical treatment (ie, surgery or radiation therapy; odds ratio, 0.49 v urban; P < .001) in patients with low-risk cancer. CONCLUSION: Patients with prostate cancer who live in rural versus urban areas experience several differences in care that are likely clinically meaningful, including fewer cores in the diagnostic biopsy, less utilization of multidisciplinary consultation, less use of active surveillance, or observation for low-risk disease. Future studies are needed to assess the efficacy of interventions in mitigating these disparities.

A targeted fluorescent nanosensor for ratiometric pH sensing at the cell surface.

The correlation between altered extracellular pH and various pathological conditions, including cancer, inflammation and metabolic disorders, is well known. Bulk pH measurements cannot report the extracellular pH value at the cell surface. However, there is a limited number of suitable tools for measuring the extracellular pH of cells with high spatial resolution, and none of them are commonly used in laboratories around the world. In this study, a versatile ratiometric nanosensor for the measurement of extracellular pH was developed. The nanosensor consists of biocompatible polystyrene nanoparticles loaded with the pH-inert reference dye Nile red and is surface functionalized with a pH-responsive fluorescein dye. Equipped with a targeting moiety, the nanosensor can adhere to cell membranes, allowing direct measurement of extracellular pH at the cell surface. The nanosensor exhibits a sensitive ratiometric pH response within the range of 5.5-9.0, with a calculated pKa of 7.47. This range optimally covers the extracellular pH (pHe) of most healthy cells and cells in which the pHe is abnormal, such as cancer cells. In combination with the nanosensors ability to target cell membranes, its high robustness, reversibility and its biocompatibility, the pHe nanosensor proves to be well suited for in-situ measurement of extracellular pH, even over extended time periods. This pH nanosensor has the potential to advance biomedical research by improving our understanding of cellular microenvironments, where extracellular pH plays an important role.

High-volume prostate biopsy core involvement is not associated with an increased risk of cancer recurrence following 5-fraction stereotactic body radiation therapy monotherapy.

PURPOSE: Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS: A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS: From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS: With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation.

Purpose: Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. Methods and materials: A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan-Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. Results: A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Conclusion: Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity.

Evaluation of a New Cystoscopic Cryocatheter and Method for the In Situ Destruction of Bladder Cancer: Preliminary In Vivo Study.

Purpose: To assess the ability to deliver full-thickness bladder wall cryoablation through a cystoscopic approach using a new closed-loop 6F cryocatheter and thermal dose-controlled protocol. Materials and Methods: Evaluations were conducted using a chronic porcine model wherein 10 lesions/animal were created throughout the bladder (bladder wall, trigone region, ureteral orifice, and distal ureter). A 6F cryocatheter was passed through the working channel of a flexible cystoscope. Single 1- and 1.5-minute freeze protocols in a saline environment were evaluated and resultant lesion size was determined. A laparoscopic approach was utilized to observe the transmural extension of the ice propagation. Results: Studies demonstrated the generation of transmural lesions characterized by full-thickness histologic necrosis after freezing for 1.5 minutes regardless of tissue thickness (range 2-12 mm). All animals were found to have good overall health (maintained weight, appetite, mobility, and energy levels) throughout the recovery period. No significant deviations were noted in complete blood count and serum chemistry bloodwork except for elevated creatine kinase levels. Importantly, no fistulas or perforations were noted. Conclusions: The cryocatheter was able to rapidly and effectively freeze the bladder wall through a cystoscopic approach. The results showed the ability to consistently ablate an ∼1 cm diameter and up to 1.2 cm deep using a single 1.5-minute freeze protocol. Analysis of the ablation efficacy revealed ∼80% destruction within the frozen mass. Although further testing and refinement are needed, these studies demonstrate the potential of this new approach to provide a next-generation strategy for the treatment of bladder cancer.

Ticagrelor vs Clopidogrel in Acute Myocardial Infarction Patients With a History of Ischemic Stroke.

OBJECTIVE: To investigate whether use of ticagrelor compared to clopidogrel is associated with different risks for thrombotic events or major bleeding among acute myocardial infarction (AMI) patients with a prior history of acute ischemic stroke. PATIENTS AND METHODS: This retrospective cohort study used the Health and Welfare Database in Taiwan. Stroke patients prescribed ticagrelor plus aspirin or clopidogrel plus aspirin after a primary hospitalization for AMI between July 1, 2013, and December 31, 2018, were included. Inverse probability of treatment weighting was applied to balance covariates between treatment groups. The primary effectiveness outcome included a composite measure of AMI, acute ischemic stroke, or all-cause mortality. The primary safety outcome included a composite measure of intracranial hemorrhage (ICH) and major gastrointestinal bleeding. The secondary effectiveness and safety outcomes comprised each of the individual components that make up the primary effectiveness and safety outcomes, respectively. RESULTS: A total of 1691 eligible patients were included in the study, of whom 734 (43.4%) received ticagrelor plus aspirin and 957 received clopidogrel plus aspirin. There were no significant differences observed in the primary and secondary effectiveness outcomes between the two study groups. However, the use of ticagrelor was associated with a higher risk of ICH (ticagrelor: 8.68 per 1000 person-year; clopidogrel: 2.17 per 1,000 person-year; HR, 3.34; 95% CI, 1.27 to 8.81, P = .01) compared with clopidogrel. CONCLUSION: In AMI patients with a history of acute ischemic stroke, the risks of cardiovascular events were comparable between ticagrelor plus aspirin and clopidogrel plus aspirin. However, ticagrelor was associated with a higher risk of ICH. Ticagrelor should be used cautiously in AMI patients with a history of acute ischemic stroke.

Stereotactic Body Radiation Therapy for the Curative Treatment of Prostate Cancer in Ultralarge (≥100 cc) Glands.

PURPOSE: Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS: We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS: Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS: With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.

Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Telehealth use and perceptions among prostate cancer survivors.

BACKGROUND: Reasons underlying disparities in telehealth use among cancer survivors are unknown. METHODS: We surveyed a sociodemographically diverse population-based cohort of 487 prostate cancer survivors regarding their use and perceptions of telehealth during the COVID-19 pandemic. RESULTS: Overall, only 28.5% of survivors had used telehealth at the time of survey and just 10% felt care through telehealth is comparable to that of an in-person visit. Still, over 55% felt telehealth is a good option for initial consultations or basic care and 15% felt more likely to use telehealth since the pandemic. After adjusting for other socioeconomic factors, survivors with lower education (≤high school vs. any college) had marginally lower use of telehealth (risk ratio [RR], 0.65 [95% CI, 0.42-1.01]) and lower probability of feeling more likely to use telehealth since the pandemic (RR, 0.39 [95% CI, 0.20-0.77]). CONCLUSIONS: Differences in survivor perceptions of telehealth by education level highlight new insights underlying disparities in telehealth use and potential targets for interventions.

Income level and treatment selection in prostate cancer: analysis of a North Carolina population-based cohort.

BACKGROUND: Disparities in treatment selection based on socioeconomic status for prostate cancer exist. However, the association between patient-level income with treatment selection priorities and treatment received has not been studied. METHODS: A population-based cohort of 1382 individuals with newly diagnosed prostate cancer was enrolled throughout North Carolina prior to treatment. Patients self-reported household income and were asked about the importance of 12 factors contributing to their treatment decision-making process. Diagnosis details and primary treatment received were abstracted from medical records and cancer registry data. RESULTS: Patients with lower income were diagnosed with more advanced disease (P < .01). Cure was deemed to be "very important" by more than 90% of patients at all income levels. However, patients with lower vs higher household income were more likely to rate factors beyond cure as "very important" such as cost (P < .01), effect on daily activities (P = .01), duration of treatment (P < .01), recovery time (P < .01), and burden on family and friends (P < .01). On multivariable analysis, high vs low income was associated with increased utilization of radical prostatectomy (odds ratio = 2.01, 95% confidence interval = 1.33 to 3.04; P < .01) and decreased use of radiotherapy (odds ratio = 0.48, 95% confidence interval = 0.31 to 0.75; P < .01). CONCLUSIONS: New insights from this study on the association between income and treatment decision-making priorities provide potential avenues for future interventions to reduce disparities in cancer care.

Cardiovascular disease prevention and management of pre-existent cardiovascular disease in a cohort of prostate cancer survivors.

PURPOSE: Cardiovascular disease (CVD) is a common cause of mortality among men with prostate cancer. However, receipt of preventive care and management of pre-existent CVD has not been well studied in prostate cancer survivors. METHODS: This study examined a prospective cohort of men newly diagnosed with localized prostate cancer between 2011 and 2013 throughout North Carolina linked to Medicare and private insurance claims and clinical data from the Veterans Affairs (VA). In patients without pre-existent CVD, the primary outcome was a composite measure of annual preventive care (blood glucose screening, cholesterol level testing, and ≥ 1 primary care provider visit). In patients with pre-existent CVD, the primary outcome was annual cardiologist visit; blood glucose, cholesterol level testing, and primary care visits were also assessed. RESULTS: Our sample comprised 492 patients successfully linked to insurance claims and/or VA data, among whom 103 (20.9%) had pre-existent CVD. Receipt of preventive care declined from 52.7% (95% confidence interval [CI], 47.7 to 57.6%) during the first year after prostate cancer diagnosis to 40.8% (95% CI: 33.7 to 48.4%) during the third year. Among patients with pre-existent CVD, only 23.4% (95% CI: 13.6 to 37.2%) visited a cardiologist in all 3 years. Black men were more likely than White men to visit a cardiologist the first year (risk ratio [RR] = 1.72, 95% CI: 1.10 to 2.71). CONCLUSION: In a population-based cohort of prostate cancer survivors, receipt of CVD preventive care declined over time, and frequency of cardiologist-led management of pre-existent CVD was low. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to improve clinical strategies for reducing cardiovascular risk and managing pre-existent CVD in prostate cancer survivors.

An Evaluation of Sexual Function in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia in Men Treated with the Temporarily Implanted Nitinol Device.

Purpose: To document the effect of the temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Israel) on sexual function from a multicenter, randomized, single-blinded, sham-controlled trial. Materials and Methods: Men were randomized 2:1 between iTind and sham procedure arms. The iTind was placed for 5-7 days and an 18F Foley catheter was inserted and removed for the iTind and sham group, respectively. Patients were assessed at baseline, 3, and 12 months postoperatively using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF). Unblinding occurred at 3 months. Results: We studied 185 men with a mean age of 61.1 ± 6.5 years. There was no difference in SHIM or total IIEF between iTind and sham at 3 months or in the iTind arm at 12 months compared with baseline. Men in the iTind arm without erectile dysfunction at baseline showed an improvement in total IIEF score of +6.07 ± 21.17 points (p = 0.034) at 12 months, in addition to an improvement in ejaculatory function. SHIM scores remained unchanged in all groups, regardless of age, prostate volume, or baseline erectile function. Conclusion: No changes were observed in sexual and ejaculatory function of patients with iTind regardless of a man's age, prostate volume, and baseline sexual function. Clinicaltrials.gov: NCT02506465.

Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics.

Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 µm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability.

Androgen Deprivation Therapy for Prostate Cancer: Focus on Cognitive Function and Mood.

Prostate cancer is the second leading cause of cancer death in men in the United States. Androgen deprivation therapy (ADT) is currently the primary treatment for metastatic prostate cancer, and some studies have shown that the use of anti-androgen drugs is related to a reduction in cognitive function, mood changes, diminished quality of life, dementia, and possibly Alzheimer's disease. ADT has potential physiological effects such as a reduction in white matter integrity and a negative impact on hypothalamic functions due to the lowering of testosterone levels or the blockade of downstream androgen receptor signaling by first- and second-generation anti-androgen drugs. A comparative analysis of prostate cancer patients undergoing ADT and Alzheimer patients identified over 30 shared genes, illustrating common ground for the mechanistic underpinning of the symptomatology. The purpose of this review was to investigate the effects of ADT on cognitive function, mood, and quality of life, as well as to analyze the relationship between ADT and Alzheimer's disease. The evaluation of prostate cancer patient cognitive ability via neurocognitive testing is described. Future studies should further explore the connection among cognitive deficits, mood disturbances, and the physiological changes that occur when hormonal balance is altered.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Patients with Bacillus Calmette­Guérin (BCG)­unresponsive non­muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell­activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan­Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan­Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer­specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Antipsychotic Use in Early Pregnancy and the Risk of Maternal and Neonatal Complications.

OBJECTIVE: To assess the association between antipsychotic use in early pregnancy and the risk of maternal and neonatal metabolic complications. METHODS: We conducted a population-based retrospective cohort study (January 1, 2010, to December 31, 2016) using the Health and Welfare Database in Taiwan. Pregnant women (18 to 49 years of age) were grouped as antipsychotic users (ie, received oral antipsychotic monotherapy during the first 20 weeks of pregnancy) and nonusers. Antipsychotic users were further categorized into first-generation antipsychotic and second-generation antipsychotic users. Propensity score methods, including matching and inverse probability of treatment weighting, were used to balance covariates. Conditional logistic regression and Cox proportional hazards models were used to compare risks of maternal (gestational diabetes mellitus, preterm birth) and neonatal (low birth weight [LBW], macrosomia) outcomes. RESULTS: Antipsychotic users had a notably higher risk of preterm birth compared with nonusers (adjusted HR, 1.29; 95% CI, 1.04 to 1.60), but the risk of gestational diabetes mellitus (HR, 1.21; 95% CI, 0.94 to 1.56), LBW (odds ratio [OR], 1.07; 95% CI, 0.84 to 1.37), and macrosomia (OR, 1.36; 95% CI, 0.63 to 2.92) did not differ between the two groups. Among women who received antipsychotics, the odds of LBW were significantly higher in second-generation antipsychotic users compared with first-generation antipsychotic users (adjusted OR, 1.32; 95% CI, 1.04 to 1.68). CONCLUSION: This study found that using antipsychotics in early pregnancy did not result in a greater risk of metabolic complications both for mothers and newborns. For women requiring treatment with antipsychotics during pregnancy, they should be monitored for the risk of preterm birth and low infant birth weight.

Effect of Prostate Volume and Minimum Tumor Temperature on 4-Year Quality-of-Life After Focal Cryoablation Compared with Active Surveillance in Men with Prostate Cancer.

Background: The purpose of this study is to analyze quality-of-life (QoL) metrics in men treated with focal cryoablation (FC) compared with active surveillance (AS) for localized prostate cancer over a 4-year follow-up period. We further investigated the effect of prostate size and minimum tumor temperature on QoL outcomes. Methods: An Institutional Review Board-approved database was reviewed for patients who underwent FC or AS. QoL questionnaire responses were collected and scores were analyzed for differences between FC and AS, between prostate volume <50 cc and ≥50 cc, and "cold" (<-78°C) and "warm" (≥-78°C) tumor temperatures. Results: One hundred forty-eight AS and 60 FC patients were included. Compared with AS, no significant difference existed in urinary function (UF) measured by Expanded Prostate Cancer Index Composite (EPIC) (p = 0.593) and International Prostate Symptom Score (IPSS) (p = 0.241), bowel habits (p = 0.370), or anxiety (p = 0.672) across time post-FC. FC had significantly worse sexual function (SF) compared with AS measured by EPIC (p < 0.0001) and International Index of Erectile Function (IIEF) (p < 0.0001). Patients with prostate volume <50 cc did not demonstrate differences between AS and FC in UF on EPIC (p = 0.459) or IPSS (p = 0.628), but FC patients had worse SF on EPIC (p < 0.001) and IIEF (p < 0.001). FC patients with a prostate volume ≥50 cc had better UF measured by IPSS (p < 0.05) and similar SF on EPIC (p = 0.162) and IIEF (p = 0.771) compared with AS. UF over time measured by EPIC (0.825) and IPSS (p = 0.658) was the same between AS, "warm," and "cold" FC groups. AS had significantly better SF than the "warm" and "cold" FC groups on EPIC (p < 0.001) and IIEF (p < 0.05). Conclusions: No differences were found in anxiety, urinary, or bowel function between AS and FC. Despite differences in SF, patients with larger prostates had no difference in SF and improved UF compared with AS. Future studies with larger cohorts are needed.

The Johns Hopkins University Center for Systems Science and Engineering COVID-19 Dashboard: data collection process, challenges faced, and lessons learned.

On Jan 22, 2020, a day after the USA reported its first COVID-19 case, the Johns Hopkins University Center for Systems Science and Engineering (JHU CSSE) launched the first global real-time coronavirus surveillance system: the JHU CSSE COVID-19 Dashboard. As of June 1, 2022, the dashboard has served the global audience for more than 30 consecutive months, totalling over 226 billion feature layer requests and 3·6 billion page views. The highest daily record was set on March 29, 2020, with more than 4·6 billion requests and over 69 million views. This Personal View reveals the fundamental technical details of the entire data system underlying the dashboard, including data collection, data fusion logic, data curation and sharing, anomaly detection, data corrections, and the human resources required to support such an effort. The Personal View also covers the challenges, ranging from data visualisation to reporting standardisation. The details presented here help develop a framework for future, large-scale public health-related data collection and reporting.

Effectiveness and Safety of Clopidogrel vs Aspirin in Elderly Patients With Ischemic Stroke.

OBJECTIVE: To evaluate the risks of recurrent stroke and major bleeding events with clopidogrel and aspirin use among patients aged 80 years or older. PATIENTS AND METHODS: This retrospective cohort study was conducted using the Full Population Data of the Health and Welfare Database in Taiwan. Patients aged 80 years or older who received monotherapy with clopidogrel or aspirin following hospitalization for primary acute ischemic stroke between January 1, 2009, and December 31, 2018, were included. Inverse probability of treatment weighting was used to balance measured covariates between clopidogrel and aspirin users. Measured outcomes included recurrent acute ischemic stroke, acute myocardial infarction, composite cardiovascular events (recurrent stroke or acute myocardial infarction), intracranial hemorrhage, major gastrointestinal tract bleeding, and composite major bleeding events (intracranial hemorrhage or major gastrointestinal tract bleeding). RESULTS: A total of 15,045 patients were included in the study, 1979 of whom used clopidogrel and 13,066 who used aspirin following hospitalization for primary acute ischemic stroke. Clopidogrel use was associated with significantly lower risk of recurrent acute ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.83 to 0.96; P=.002), composite cardiovascular events (HR, 0.88; 95% CI, 0.82 to 0.95; P<.001), intracranial hemorrhage (HR, 0.71; 95% CI, 0.56 to 0.90; P=.005), and composite major bleeding events (HR, 0.89; 95% CI, 0.80 to 0.99; P=.04) compared with aspirin use. CONCLUSION: In patients aged 80 years or older with primary acute ischemic stroke, clopidogrel users had lower risks of recurrent stroke and the composite cardiovascular events compared with aspirin users. Clopidogrel users also had lower risks of intracranial hemorrhage and the composite major bleeding events compared with aspirin users.