Evaluating the Impact of a Pharmacist-Led Antimicrobial Stewardship Intervention at Discharge in a Community, Nonteaching Hospital.

INTRODUCTION: Approximately 30% to 50% of hospital discharge antimicrobials are inappropriate. Limited data exist on approaches to improve antimicrobial prescribing practices at the time of discharge from a community hospital. Objective: To assess the impact of a comprehensive pharmacist-led antimicrobial stewardship intervention at discharge. METHODS: We conducted a quasi-experimental, pre-post study. A biphasic intervention took place on 2 medicine units from November 2019 to May 2020 at a community hospital. Baseline data were collected, followed by prescriber education on antimicrobial stewardship to both units (education phase). Next, a pharmacist-led intervention took place on one unit (intervention phase). The primary outcome was composite appropriateness of an oral antimicrobial prescribed to an adult at the time of discharge, defined by narrow spectrum of activity, dosing, and duration of therapy. The primary outcome was assessed using Fisher exact test. RESULTS: Baseline composite appropriateness was 30% (n = 12) on the control unit and 30.8% (n = 20) on the intervention unit. From baseline to posteducation, no significant change in composite appropriateness was found on the control (30% to 26.7%, P = 0.256) or intervention (30.8% to 19.4%, P = 0.09) unit. There was no significant difference between the education to intervention phase (26.7% vs 35%, P = 0.254) on the control unit. On the intervention unit, a significant difference in composite appropriateness was found from the education to intervention phase (19.4% vs 47.8%, P = 0.017). CONCLUSION AND RELEVANCE: A pharmacist-led intervention improved appropriateness of oral antimicrobials prescribed at discharge. One-time education was insufficient for improving antimicrobial stewardship.

Temperature Management and Health-Related Quality of Life in Children 3 Years After Cardiac Arrest.

OBJECTIVES: Therapeutic hypothermia minimizes neuronal injury in animal models of hypoxic-ischemic encephalopathy with greater effect when used sooner after the insult. Clinical trials generally showed limited benefit but are difficult to perform in a timely manner. In this clinical study, we evaluated the association between the use of hypothermia (or not) and health-related quality of life among survivors of pediatric cardiac arrest as well as overall mortality. DESIGN: Single-center, retrospectively identified cohort with prospective assessment of health-related quality of life. SETTING: PICU of a pediatric hospital. PATIENTS: Children with either out-of-hospital or in-hospital cardiac arrest from January 2012 to December 2017. INTERVENTIONS: Patients were assigned into two groups: those who received therapeutic hypothermia at less than or equal to 35°C and those who did not receive therapeutic hypothermia but who had normothermia targeted (36-36.5°C). The primary outcome was health-related quality of life assessment and the secondary outcome was PICU mortality. MEASUREMENTS AND MAIN RESULTS: We studied 239 children, 112 (47%) in the therapeutic hypothermia group. The median (interquartile range) of lowest temperature reached in the 48 hours post cardiac arrest in the therapeutic hypothermia group was 33°C (32.6-33.6°C) compared with 35.4°C (34.7-36.2°C) in the no therapeutic hypothermia group (p < 0.001). At follow-up, 152 (64%) were alive and health-related quality of life assessments were completed in 128. Use of therapeutic hypothermia was associated with higher lactate and lower pH at baseline. After regression adjustment, therapeutic hypothermia (as opposed to no therapeutic hypothermia) was associated with higher physical (mean difference, 15.8; 95% CI, 3.5-27.9) and psychosocial scores (13.6 [5.8-21.5]). These observations remained even when patients with a temperature greater than 37.5°C were excluded. We failed to find an association between therapeutic hypothermia and lower mortality. CONCLUSIONS: Out-of-hospital or in-hospital cardiac arrest treated with therapeutic hypothermia was associated with higher health-related quality of life scores despite having association with higher lactate and lower pH after resuscitation. We failed to identify an association between use of therapeutic hypothermia and lower mortality.

Exploratory descriptive analysis of opioid prescribing prevalence of nurse practitioners and the specialties associated with the top prescribers.

BACKGROUND: Opioid prescription drug abuse is increasingly becoming a concern beyond the United States. Little is known regarding nurse practitioners' opioid prescribing patterns or settings. AIM: To examine nurse practitioners' opioid prescription patterns. METHODS: We conducted a retrospective cross-sectional descriptive study of the 2016 Medicare Part D Prescriber Public Use File and analysed the association between the number of nurse practitioners and the number of opioid prescriptions. We conducted Web searches on the top 1% of prescribers to obtain the specialty areas in which nurse practitioners worked. RESULTS: There was no significant correlation between the prevalence of nurse practitioners and the opioid prescription rates among the states in the United States. Most nurse practitioners do not prescribe opioids. Opioid prescription is highly concentrated among nurse practitioners, as 1% of nurse practitioners account for one third of opioids prescribed by nurse practitioners. Most of the top 1% opioid prescribers practice in specialty care with board-certified pain medicine physicians. CONCLUSIONS: The prevalence of nurse practitioners is not likely a significant contributing factor to the opioid epidemic. Rather than increased scrutiny of opioid prescribing, a better approach to curb the opioid crisis might be to facilitate collaboration among physicians, nurse practitioners and patients.

An examination of opioid prescription for Medicare Part D patients among family practice prescribers.

BACKGROUND: In the USA, opioid overdose accounted for more than 60% of drug overdose deaths in 2015. Of these deaths, 40% were due to use of prescription opioids. OBJECTIVES: The aims of the study were to (i) study family medicine physician opioid-prescribing rate and duration of prescription, (ii) study the distribution of prescription by medication potency, (iii) study opioid-prescribing trends in health care shortage areas and (iv) study the association between extreme high prescribing rates and medical board discipline. METHODS: This is a retrospective cross-sectional study of the 2015 Medicare Part D claim data. RESULTS: Family practitioners have opioid prescription rates (5.6%) similar to medical subspecialists (6.0%), but lower than pain specialists (53.2%) and surgical specialists (36.6%). Family practitioners have an average opioid prescription duration (21.5 days) similar to medical subspecialists (23.1 days) and pain specialists (27.1 days), but longer than surgical specialists (8.9 days). Family practitioners tend to prescribe lower potency opioids. Family practitioners in rural health care shortage areas have a higher opioid prescription rate than other family practitioners (6.5% versus 5.6%). Among the 52 family practitioners who prescribed opioids as frequently as pain specialists, 26 of the 52 (50%) were certified in pain management or worked with a partner certified in pain management. Of the other 26 family practitioners, 3 (12%) had medical board disciplinary actions regarding opioid prescription. CONCLUSIONS: While monitoring extreme prescribers is important and needs to be continued, the next step in policies to reduce prescription opioids will require systemic change, especially providing support for family practitioners in rural health care shortage areas.

Clinical Effects of Nitric Oxide Added to the Oxygenator of Children on Extracorporeal Membrane Oxygenation: Pre-Post Cohort Study.

Nitric oxide (NO) can be safely delivered through the sweep gas to the oxygenator of an extracorporeal membrane oxygenation (ECMO) circuit. It has theoretical benefits such as preventing platelet adhesion to surfaces, mitigating inflammatory response and protection against ischemia-reperfusion injury. In this uncontrolled before-after study of children on ECMO, the outcomes of those who received NO were compared with those who did not. Among 393 ECMO runs (from 337 patients), 192 of 393 (49%) received NO and 201 of 393 (51%) did not. The use of NO was associated with a 37% reduction in circuit change (adjusted risk ratio [aRR]: 0.63, 95% confidence interval [CI]: 0.42-0.93). The aRR (95% CI) for risk of neurologic injury was 0.72 (0.47-1.11). We observed potential heterogeneity of treatment effect for the risk of neurologic injury in children who had cardiac surgery: the risk with NO was lower in those who had cardiac surgery (aRR: 0.50, 95% CI: 0.26-0.96). There was no difference in survival between the study groups. In children managed with NO delivered through the ECMO circuit, we report a reduction in observed rate of circuit change and lower risk of neurologic injury in children who underwent cardiac surgery. Nitric oxide therapy on ECMO warrants prospective evaluation in children.

A Continuing Pharmacy Education (CPE) Program Assessing Cannabidiol (CBD) Knowledge and Confidence Among Practicing Pharmacists.

Background: Increased patient utilization of cannabidiol (CBD) leads to potential drug interactions with various medications and questions posed to pharmacists. Objective: To quantify the knowledge gap of pharmacists on CBD and CBD-containing products and assess the degree a continuing pharmacy education (CPE) program alters pharmacist confidence and competency on CBD knowledge. Methods: A 1-h CPE activity was offered as a home study from May 9, 2022, through September 30, 2022. Subjects were practicing pharmacy preceptors in Alabama who completed the pre-survey and post-survey for inclusion in matched-pair analyses. The primary outcome measure was participant score improvement between the pre-post surveys. Secondary measures involved pre-post comparisons on self-rated Likert questions concerning participant confidence in counseling, answering drug information questions, and ensuring patient safety regarding CBD. Results: A total of 124 participants completed the course. After matched pairing, 64 and 56 individuals were included in the knowledge-based and confidence ranking analyses, respectively. Participant scoring improved on the knowledge-based questions between the pre-post surveys (50.0% vs 87.8%, P < .001). There was a significant confidence improvement of participants from baseline on counseling patients about prescription or over-the-counter CBD products, answering questions from other healthcare professionals about these products, and ensuring patient safety while using these products (Average 5-level Likert scale increases of 1.75, 1.73, 1.70, respectively; all P < .001). Conclusion: Implementation of a CPE program improved practicing pharmacists' knowledge on information about CBD, which lead to increased competency on counseling patients, answering drug information questions, and promoting patient safety.

Reliable Detection of Eczema Areas for Fully Automated Assessment of Eczema Severity from Digital Camera Images.

Assessing the severity of eczema in clinical research requires face-to-face skin examination by trained staff. Such approaches are resource-intensive for participants and staff, challenging during pandemics, and prone to inter- and intra-observer variation. Computer vision algorithms have been proposed to automate the assessment of eczema severity using digital camera images. However, they often require human intervention to detect eczema lesions and cannot automatically assess eczema severity from real-world images in an end-to-end pipeline. We developed a model to detect eczema lesions from images using data augmentation and pixel-level segmentation of eczema lesions on 1,345 images provided by dermatologists. We evaluated the quality of the obtained segmentation compared with that of the clinicians, the robustness to varying imaging conditions encountered in real-life images, such as lighting, focus, and blur, and the performance of downstream severity prediction when using the detected eczema lesions. The quality and robustness of eczema lesion detection increased by approximately 25% and 40%, respectively, compared with that of our previous eczema detection model. The performance of the downstream severity prediction remained unchanged. Use of skin segmentation as an alternative to eczema segmentation that requires specialist labeling showed the performance on par with when eczema segmentation is used.

Pharmacy Students' Attitudes and Perceptions toward Financial Management Education.

(1) Background: Pharmacy-related financial management training and education are an integral part of the pharmacy curriculum. This study aims to evaluate pharmacy students' perceptions toward financial management education, their attitudes on its clinical relevance, and their ability to use financial management knowledge in introductory and advanced pharmacy practice experiences. (2) Methods: An online survey was sent to third- and fourth-year pharmacy students. The survey assessed the following three themes: perceptions toward financial management education; attitudes toward the clinical relevance of financial management education; and the student's ability to use knowledge of financial management in practice. Descriptive statistics were used to summarize the data. (3) Results: The overall response rate for the survey was 60% (139/233). Overall, the study showed a positive perception and attitude toward financial management education. Results indicate that pharmacy students were confident in their ability to use financial management knowledge in pharmacy practice. (4) Conclusions: This survey found an overall optimism in financial management education's role in pharmacy practice and the ability to obtain financial management competencies in professional pharmacy training. With the evolving practice requirements, pharmacy schools should adapt their financial management curricula with relevant skills to prepare students to become effective entrepreneurs, innovators, and practice leaders.

CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy.

Adoptive cell therapy with chimeric antigen receptor (CAR) immunotherapy has made tremendous progress with five CAR T therapies approved by the US Food and Drug Administration for hematological malignancies. However, CAR immunotherapy in solid tumors lags significantly behind. Some of the major hurdles for CAR immunotherapy in solid tumors include CAR T cell manufacturing, lack of tumor-specific antigens, inefficient CAR T cell trafficking and infiltration into tumor sites, immunosuppressive tumor microenvironment (TME), therapy-associated toxicity, and antigen escape. CAR Natural Killer (NK) cells have several advantages over CAR T cells as the NK cells can be manufactured from pre-existing cell lines or allogeneic NK cells with unmatched major histocompatibility complex (MHC); can kill cancer cells through both CAR-dependent and CAR-independent pathways; and have less toxicity, especially cytokine-release syndrome and neurotoxicity. At least one clinical trial showed the efficacy and tolerability of CAR NK cell therapy. Macrophages can efficiently infiltrate into tumors, are major immune regulators and abundantly present in TME. The immunosuppressive M2 macrophages are at least as efficient as the proinflammatory M1 macrophages in phagocytosis of target cells; and M2 macrophages can be induced to differentiate to the M1 phenotype. Consequently, there is significant interest in developing CAR macrophages for cancer immunotherapy to overcome some major hurdles associated with CAR T/NK therapy, especially in solid tumors. Nevertheless, both CAR NK and CAR macrophages have their own limitations. This comprehensive review article will discuss the current status and the major hurdles associated with CAR T and CAR NK therapy, followed by the structure and cutting-edge research of developing CAR macrophages as cancer-specific phagocytes, antigen presenters, immunostimulators, and TME modifiers.

Detecting Eczema Areas in Digital Images: An Impossible Task?

Assessing the severity of atopic dermatitis (AD, or eczema) traditionally relies on a face-to-face assessment by healthcare professionals and may suffer from inter- and intra-rater variability. With the expanding role of telemedicine, several machine learning algorithms have been proposed to automatically assess AD severity from digital images. Those algorithms usually detect and then delineate (segment) AD lesions before assessing lesional severity and are trained using the data of AD areas detected by healthcare professionals. To evaluate the reliability of such data, we estimated the inter-rater reliability of AD segmentation in digital images. Four dermatologists independently segmented AD lesions in 80 digital images collected in a published clinical trial. We estimated the inter-rater reliability of the AD segmentation using the intraclass correlation coefficient at the pixel and the area levels for different resolutions of the images. The average intraclass correlation coefficient was 0.45 ( standard error = 0.04 ) corresponding to a poor agreement between raters, whereas the degree of agreement for AD segmentation varied from image to image. The AD segmentation in digital images is highly rater dependent even among dermatologists. Such limitations need to be taken into consideration when AD segmentation data are used to train machine learning algorithms that assess eczema severity.

Survival Trends of Metastatic Lung Cancer in California by Age at Diagnosis, Gender, Race/Ethnicity, and Histology, 1990-2014.

BACKGROUND: We analyzed the survival trends for patients with metastatic lung cancer in California. MATERIALS AND METHODS: We identified patients first diagnosed with primary lung cancer at distant (metastatic) stage in the California Cancer Registry between 1990 and 2014, with follow-up through end of 2015. Race/ethnicity was categorized into non-Hispanic white, non-Hispanic black, Hispanic, and Asian/Pacific Islander. One-year and 5-year relative survival rates were calculated overall and by age at diagnosis, gender, race/ethnicity, and histology during the study period. Joinpoint regression was used to evaluate the trends and to calculate the annual percentage changes (APCs). RESULTS: A total of 186,156 adults were identified for analysis. Between 1990 and 2014, 1-year relative survival significantly improved from 18.4% to 29.4%, with most improvement observed between 1993 and 2012 (APC, 2.60%; 95% confidence interval, 2.41-2.79; P < .01). Five-year relative survival significantly improved from 2.2% to 5.0%, with an APC of 4.05% (95% confidence interval, 3.47-4.64; P < .01). All age groups experienced an improvement in survival rates. The greatest increases in relative survival were observed among females, Asian/Pacific Islanders, and patients with adenocarcinoma. Yearly survival rates increased for all histologic types over the study period, with adenocarcinoma having the most improvement after 2000. CONCLUSIONS: Survival for patients with metastatic lung cancer in California steadily improved during the 1990 to 2014 period, before the era of lung cancer screening and cancer immunotherapy. The greatest increase in relative survival was observed in those patients who have the most clinical benefit from the history- and biomarker-based precision oncology drugs during the study period.

Role of levosimendan in weaning children requiring veno-arterial extracorporeal membrane oxygenation after cardiac surgery.

OBJECTIVES: Levosimendan use is associated with more successful decannulation from veno-arterial extracorporeal membrane oxygenation (VA ECMO) in adults. We sought to determine the role of levosimendan in children who required VA ECMO after cardiac surgery. METHODS: This observational study compares the outcomes of children who required VA ECMO after cardiac surgery and received levosimendan for weaning with those who did not receive the drug. A doubly robust estimation methodology (inverse probability of treatment weighting with regression adjustment) was used to balance study covariates (age, weight, sex, lactate pre-ECMO, vasoactive-inotropic score pre-ECMO, ECMO indication, ECMO modality, Risk Adjustment for Congenital Heart Surgery-1 category), and the final model was further adjusted for duration of ECMO. RESULTS: Between January 2012 and December 2018, 118 eligible children received 145 ECMO runs [failed weaning from cardiopulmonary bypass, 67/145 (46%); low cardiac output state, 30/145 (21%); extracorporeal cardiopulmonary resuscitation, 47/145 (32%); other reasons in 1]. Levosimendan was administered before decannulation in 54/145 (37%) runs. The median time to start levosimendan after ECMO cannulation was 39 h (interquartile range, 14-83 h). The unadjusted rates of weaning failure in the levosimendan vs control group were 7% (4/54) vs 19% (17/91). In the controlled analysis, levosimendan was associated with decreased risk of weaning failure [adjusted relative risk (95% confidence interval), 0.20 (0.07-0.57)] and decreased risk of in-hospital mortality [adjusted relative risk (95% confidence interval), 0.45 (0.26-0.76)]. CONCLUSIONS: Levosimendan administration in children requiring VA ECMO after cardiac surgery was associated with decreased risk of weaning failure and decreased in-hospital mortality.

Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling.

Tumor recurrence is the major obstacle for pushing the envelope of liver transplantation for hepatocellular carcinoma (HCC) patients. The inflammatory cascades activated by acute liver graft injury promote tumor recurrence. We aimed to explore the role and mechanism of myeloid-derived suppressor cell (MDSC) mobilization induced by liver graft injury on tumor recurrence. By analyzing 331 HCC patients who received liver transplantation, the patients with graft weight ratio (GWR, the weight of liver graft divided by the estimated standard liver weight of recipient) <60% had higher tumor recurrence than GWR ≥60% ones. MDSCs and CXCL10/TLR4 levels were significantly increased in patients with GWR <60% or tumor recurrence. These findings were further validated in our rat orthotopic liver transplantation model. In CXCL10-/- and TLR4-/- mice of hepatic ischemia/reperfusion injury plus major hepatectomy (IRH) model, monocytic MDSCs, instead of granulocytic MDSCs, were significantly decreased. Importantly, CXCL10 deficiency reduced the accumulation of TLR4+ monocytic MDSCs, and CXCL10 increased MDSC mobilization in the presence of TLR4. Moreover, MMP14 was identified as the key molecule bridging CXCL10/TLR4 signaling and MDSC mobilization. Knockout or inhibition of CXCL10/TLR4 signaling significantly reduced the tumor growth with decreased monocytic MDSCs and MMP14 in the mouse tumor recurrent model. Our data indicated that monocytic MDSCs were mobilized and recruited to liver graft during acute phase injury, and to promote HCC recurrence after transplantation. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent the therapeutic potential in decreasing post-transplant liver tumor recurrence.

Development of cisplatin-loaded hydrogels for trans-portal vein chemoembolization in an orthotopic liver cancer mouse model.

Transarterial chemoembolization is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). This study evaluated the anti-tumor effect of the semi-interpenetrating network (IPN) hydrogel as a novel embolic material for trans-portal vein chemoembolization (TPVE) in vivo. A nude mice orthotopic HCC model was established, followed by TPVE using IPN hydrogel loaded with or without cisplatin. Portal vein blockade was visualized by MRI and the development of tumor was monitored by IVIS Spectrum Imaging. Tumor proliferation and angiogenesis were evaluated by Ki67 and CD34 staining respectively. Intra-tumor caspase 3, Akt, ERK1/2, and VEGF activation were detected by Western Blot. 18 F-FMISO uptake was evaluated by microPET-MRI scanning. IPN hydrogel first embolized the left branch of portal vein within 24 hours and further integrated into the intra-tumor vessels during 2 weeks after the treatment. Mice treated with cisplatin-loaded hydrogels exhibited a significant decrease in tumor growth, along with lower plasma AFP levels as compared to hydrogel-treated and untreated tumor-bearing mice. By Ki67 and CD34 staining, the TPVE with IPN hydrogel suppressed tumor proliferation and angiogenesis. In addition, increased tumor apoptosis shown by up-regulation of caspase 3 with decreased expressions of tumor cell survival indicators Akt and ERK1/2 were observed in the treatment groups. Consistent with the decreased expression of VEGF after TPVE, hypoxia level in the tumor was also reduced as indicated by 18 F-FMISO uptake level. IPN hydrogel-based TPVE significantly suppressed the tumor development by regulating intra-tumor angiogenesis and cell survival in an orthotopic HCC mouse model, suggesting a viable embolic agent for transarterial chemoembolization.

Analysis of psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in Medicare Part D in the United States.

INTRODUCTION: The opioid epidemic is a severe problem in the world, especially in the United States, where prescription opioid overdose accounts for a quarter of drug overdose deaths. OBJECTIVE: To describe psychiatrists' prescription of opioid, benzodiazepine, and buprenorphine in the United States. METHODS: We conducted a retrospective cross-sectional study of the 2016 Medicare Part D claims data and analyzed psychiatrists' prescriptions of: 1) opioids; 2) benzodiazepines, whose concurrent prescription with opioids can cause overdose death; 3) buprenorphine, a partial opioid agonist for treating opioid addiction; 4) and naltrexone microsphere, a once-monthly injectable opioid antagonist to prevent relapse to opioid dependence. Prescribers with 11 or more claims were included in the analysis. RESULTS: In Medicare Part D in 2016, there were a total of 1,131,550 prescribers accounting for 1,480,972,766 total prescriptions and 78,145,305 opioid prescriptions, including 25,528 psychiatrists (2.6% of all prescribers) accounting for 44,684,504 total prescriptions (3.0% of all prescriptions) and 131,115 opioid prescriptions (0.2% of all opioid prescriptions). Psychiatrists accounted for 17.3% of benzodiazepine, 16.3% of buprenorphine, and 33.4% of naltrexone microsphere prescriptions. The opioid prescription rate of psychiatrists was much lower than that of all prescribers (0.3 vs 5.3%). The buprenorphine prescription rate of psychiatrists was much higher than that of all prescribers (2.3 vs. 0.1%). There was a substantial geographical variation across the United States. CONCLUSIONS: The results show that, proportionally, psychiatrists have lower rates of opioid prescription and higher rates of benzodiazepine and buprenorphine prescription.

Variation in anthocyanin profiles of 27 genotypes of red cabbage over two growing seasons.

Acylated anthocyanins, such as those found in red cabbage, are more heat-, light-, and alkaline pH-stable than non-acylated anthocyanins, making them attractive for a variety of commercial applications. A UPLC-DAD-MSE method with an optimized chromatographic strategy was used to identify 29 red cabbage anthocyanins, predominantly acylated and glucosylated cyanidin derivatives. Anthocyanin profiles of 27 red cabbage genotypes harvested in consecutive growing seasons were measured and assessed for variation. Three unique anthocyanin profile fingerprints were identified through hierarchical clustering analysis. PCA analysis identified anthocyanin accumulation traits and genotypes with high diversity which can be utilized in future investigations into the genetic and molecular basis for anthocyanin production, acylation, and diversity.

Sociodemographic disparities in chemotherapy treatment and impact on survival among patients with metastatic bladder cancer.

OBJECTIVE: To evaluate how socioeconomic status and other demographic factors are associated with the receipt of chemotherapy and subsequent survival in patients diagnosed with metastatic bladder cancer. METHODS: Using data from the California Cancer Registry, we identified 3,667 patients diagnosed with metastatic urothelial carcinoma of the urinary bladder between 1988 and 2014. The characteristics of patients who did and did not receive chemotherapy as part of the first course of treatment were compared using chi-square tests. Logistic regression was used to identify predictors of chemotherapy treatment. Fine and Gray competing-risks regression and Cox proportional hazards regression were used to estimate bladder cancer-specific and all-cause mortality, respectively. RESULTS: Less than half (46.3%) of patients received chemotherapy. Patients from the lowest socioeconomic quintile were half as likely to have chemotherapy as those from highest quintile (odds ratio = 0.5, 95% CI: 0.4, 0.7). Unmarried patients were significantly less likely to receive treatment (odds ratio = 0.6, 95% CI: 0.5, 0.7). Not receiving chemotherapy was associated with greater mortality from bladder cancer (subdistribution hazard ratio = 1.4, 95% CI: 1.3, 1.5) and from all causes (hazard ratio = 2.0, 95% CI: 1.8, 2.1). CONCLUSIONS: We found clear disparities in chemotherapy treatment and survival with respect to socioeconomic and marital status. Future studies should explore the possible reasons why patients with low socioeconomic status and who are unmarried are less likely to have chemotherapy.

Laboratory alerts to guide early intensive care team review in surgical patients: A feasibility, safety, and efficacy pilot randomized controlled trial.

AIM: Common blood tests can help identify patients at risk of death, unplanned intensive care unit (ICU) admission, or rapid response team (RRT) call. We aimed to test whether early ICU-team review triggered by such laboratory tests (lab alert) is feasible, safe, and can alter physiological variables, clinical management, and clinical outcomes. METHODS: In prospective pilot randomized controlled trial in surgical wards of a tertiary hospital, we studied patients admitted for >24 h. We applied a previously validated risk assessment tool to each set of common laboratory tests to identify patients at risk and generate a "lab-alert". We randomly allocated such lab-alert patients to receive early ICU-team review (intervention) or usual care (control). RESULTS: We studied 205 patients (males 54.1%; average age 79 years; 103 randomized to intervention and 102 to usual care). Intervention patients were more likely to trigger RRT activation during their first lab-alert (10.7 vs. 2.0%; P < 0.001) but less likely to receive an allied health referral (18.0% vs. 24.5%; p = 0.007). They were less likely to trigger RRT activation in the 24-h before subsequent alerts (18.4 vs. 22.4%; p = 0.008) and less likely to generate further alerts (204 vs. 320; p < 0.001), but more likely to receive a not for resuscitation or endotracheal intubation status in the 24-h before subsequent alerts (26.6 vs. 17.3%; p = 0.05). Mortality at 24 h was 1.9% for the intervention group vs. 2.9% in the control group (p = 0.63). Finally, overall mortality was 19.4% for intervention patients vs. 23.5% for control patients (p = 0.50). CONCLUSION: Among surgical patients, lab alerts identify patients with a high mortality. Lab alert-triggered interventions are associated with more first alert-associated RRT activations; more changes in resuscitation status toward a more conservative approach; fewer subsequent alert-associated RRT activations; fewer subsequent alerts, and decreased allied health interventions (ANZCTRN12615000146594).

Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing.

The established urinary antibiotic nitroxoline has recently regained considerable attention, due to its potent activities in inhibiting angiogenesis, inducing apoptosis and blocking cancer cell invasion. These features make nitroxoline an excellent candidate for anticancer drug repurposing. To rapidly advance nitroxoline repurposing into clinical trials, the present study performed systemic preclinical pharmacodynamic evaluation of its anticancer activity, including a methyl thiazolyl tetrazolium assay in vitro and an orthotopic urological tumor assay in vivo. The current study determined that nitroxoline exhibits dose-dependent anti-cancer activity in vitro and in urological tumor orthotopic mouse models. In addition, it was demonstrated that the routine nitroxoline administration regimen used for urinary tract infections was effective and sufficient for urological cancer treatment, and 2 to 4-fold higher doses resulted in obvious enhancement of anticancer efficacy without corresponding increases in toxicity. Furthermore, nitroxoline sulfate, one of the most common metabolites of nitroxoline in the urine, effectively inhibited cancer cell proliferation. This finding increases the feasibility of nitroxoline repurposing for urological cancer treatment. Due to the excellent anticancer activity demonstrated in the present study, and its well-known safety profile and pharmacokinetic properties, nitroxoline has been approved to enter into a phase II clinical trial in China for non-muscle invasive bladder cancer treatment (registration no. CTR20131716).

8-(Heteroaryl)phenalkyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones as opioid receptor modulators.

A series of N-biarylalkyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones were prepared and evaluated for biological activity at opioid (mu, delta, kappa) and opioid receptor like-1 (ORL-1) G-protein coupled receptors. Substitution on the biaryl moiety produced enhanced affinity for the mu-opioid receptor.