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Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes high morbidity and mortality in older adults with chronic illnesses. Several trials are currently underway evaluating the antimalarial drug hydroxychloroquine as a potential treatment for acute infection. However, polypharmacy predisposes patients to increased risk of drug–drug interactions with hydroxychloroquine and may render many in this population ineligible to participate in trials. Objectives We aimed to quantify the degree of polypharmacy and burden of potentially inappropriate medications (PIMs) that older hospitalized adults are taking which would interact with hydroxychloroquine. Methods We reanalyzed data from the cohort of patients 65 years and older enrolled in the MedSafer pilot study. We first identified patients taking medications with potentially harmful drug–drug interactions with hydroxychloroquine that might exclude them from participation in a typical coronavirus disease 2019 (COVID‐19) therapeutic trial. Next, we identified medications that were flagged by MedSafer as being potentially inappropriate and crafted guidance around medication management if contemplating the use of hydroxychloroquine. Results The cohort contained a total of 1,001 unique patients with complete data on their home medications at admission. Of these 1,001 patients, 590 (58.9%) were receiving one or more home medications that could potentially interact with hydroxychloroquine, and of these 255 (43.2%) were flagged as potentially inappropriate by the MedSafer tool. Common classes of PIMs observed were antipsychotics, cardiac medications, and anti‐diabetic agents. Conclusion The COVID‐19 pandemic highlights the importance of medication optimization and deprescribing PIMs in older adults. By acting now to reduce polypharmacy and use of PIMs, we can better prepare this vulnerable population for inclusion in trials and, if substantiated, pharmacologic treatment or prevention of COVID‐19. This article is protected by copyright. All rights reserved.

Companies play an important role as an intermediary link between suppliers (manufacturers and importers) and customers. Relying on expert and efficient human capital, adherence to standards, as well as applying knowledge and technology are the most influential factors in driving a company's goals. One of the new tools, which helps organizations move toward their goals, is the use of marketing intelligence. Therefore, in this study, we try to analyze the impact of marketing intelligence and business intelligence on competitive advantage. The statistical population of this study consists of managers of information technology companies that 200 subjects were sampled. The main tool for data collection is questionnaire. Research findings suggest that marketing information, creativity, IQ and EQ influence marketing intelligence enhancement. Marketing intelligence also affects business intelligence and business intelligence to gain competitive advantage. Overall, this study confirms the relationship between model variables.

Objectives Polypharmacy is common, costly, and harmful for hospitalized older adults. Scalable strategies to reduce the burden of potentially inappropriate medications (PIMs) are needed. We sought to leverage medication reconciliation in hospitalized older adults by pairing with MedSafer, an electronic decision support tool for deprescribing. Design This was a nonrandomized controlled before-and-after study. Setting The study took place on four internal medicine clinical teaching units. Participants Subjects were aged 65 years and older, had an expected prognosis of 3 or more months, and were taking five or more usual home medications. Intervention In the baseline phase, patients received usual care that was medication reconciliation. Patients in the intervention arm also had a "deprescribing opportunity report" generated by MedSafer and provided to their in-hospital treating team. Measurements The primary outcome was ascertained at the time of hospital discharge and was the proportion of patients who had one or more PIMs deprescribed. Results A total of 1066 patients were enrolled, and deprescribing opportunities were present for 873 (82%; 418 during the control and 455 during the intervention phases, respectively). The proportion of patients with one or more PIMs deprescribed at discharge increased from 46.9% in the control period to 54.7% in the intervention period with an adjusted absolute risk difference of 8.3% (2.9%-13.9%). Not all classes of drugs in the intervention arm were associated with an increase in deprescribing, and new PIM starts were equally common in both arms of the study. Conclusion Using an electronic decision support tool for deprescribing, we increased the proportion of patients with one or more PIMs deprescribed at hospital discharge as compared with usual care. Although this type of intervention may help address medication overload in hospitalized patients, it also underscores the importance of powering future trials for a reduction in adverse drug events. Trial registration NCT02918058. J Am Geriatr Soc 67:1843-1850, 2019.

As an optimization problem, reactive-power compensation (RPC) in distribution networks has variety of technical and economical objectives and constraints. In order to solve the RPC problem, classic and heuristic methods have been applied. In distributed networks with large amounts of equipment, the RPC has a large dimension which could be a challenge for the aforementioned methods. So, having an initial guess or solution for buses that are suitable for compensator installation, lessens the mentioned challenge and thus improves performance of the solution procedures. Applying extended impedance matrix, this paper proposes a method to determine initial solution for the RPC problem. “Extended” means loads connected to buses are included in the impedance matrix. Inclusion of loads in the matrix gives more realistic initial solutions. The rationale behind it is that buses with more loads usually need more reactive composition. Two ranking lists of the buses that could be nominated for RPC have been considered in this paper: One list is obtained by the proposed method, and the other by the sensitivity analysis. Comparison of the mentioned lists in two typical distribution systems shows acceptable performance of the proposed method.

BACKGROUND Surgical site infections (SSIs) are the most common nosocomial infection and occur in 16.3% of patients undergoing colorectal surgery at our institution (The Ottawa Hospital), the majority of which are identified after discharge from hospital. Patients who suspect having an SSI generally present to the emergency department or surgery clinic. Both options for in-person interaction are costly to the health care system and patients. A mobile app, how2trak, has proven to be beneficial for patients with complex wounds at our institution by facilitating at-home monitoring and virtual consultations. OBJECTIVE This study aims to assess the feasibility of a randomized controlled trial to assess if how2trak can improve patients’ experience and increase detection of SSIs after colorectal surgery while reducing patients’ risk of COVID-19 exposure. METHODS In this single-center prospective feasibility trial, eligible patients undergoing colorectal surgery will be randomized to either standard care or how2trak postoperative monitoring of their incision, symptoms, and ostomy function. Patient self-assessments will be monitored by a nurse specialized in wound and ostomy care who will follow-up with patients with a suspected SSI. The primary outcome is feasibility as measured by enrollment, randomization, app usability, data extraction, and resource capacity. RESULTS This study was approved by our institution’s ethics board on February 26, 2021, and received support from The Ottawa Hospital Innovation and Care Funding on November 12, 2021. Recruitment started June 3, 2021, and 29 were patients enrolled as of September 2021. We expect to publish results in spring 2022. CONCLUSIONS This study will determine the feasibility of using a mobile app to monitor patients’ wounds and detect SSIs after colorectal surgery. If feasible, we plan to assess if this mobile app facilitates SSI detection, enhances patient experience, and optimizes their care. CLINICALTRIAL ClinicalTrials.gov NCT04869774; https://clinicaltrials.gov/ct2/show/NCT04869774 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/26717

Background The General Internal Medicine Clinical Teaching Unit (CTU) is a challenging rotation for new residents and the optimal format of orientation has not been determined. We hypothesized that an iPad® application (app) would be a useful reference tool after residents completed their traditional large group orientation. Methods Postgraduate year 1 (PGY1) residents were sent a link to download the free app one week before the start of their rotation. A pre-usage survey at initial login collected basic demographics. Usage data was collected to determine the sections, duration, and the timeframe from which the app was utilized. Results Pre-usage survey data revealed that 63% of participants were female, 69% felt the app would improve orientation, and 94% were comfortable using mobile technology for medical education. Usage data showed “Teaching Sessions and Schedules,” “The Consult Note,” and “Admission Orders” were the three sections most commonly used. The most usage was during the evening call shift (10pm to 6am), followed by the morning shift (6am to 5pm). Conclusion The CTU Orientation App was a useful supplement to the traditional orientation. Researchers may not be able to predict what content would be most valuable in an iPad® app, thus pre-development needs-assessments and usage feedback are crucial.

Background Multiple factors affect compliance with hand hygiene, including conspicuity of alcohol-gel dispensers. Previous studies have shown that flashing lights increase hand hygiene compliance; however, the durability of this effect has not been studied. Methods We affixed flashing lights to hand sanitizer dispensers for a total of 6 weeks. Regression analysis was used to compare compliance rates between the beginning and end of the intervention. Our secondary objective was to determine whether compliance rates in cold weather could be improved by adding a sign separated in time and space from the dispensers. Results Flashing lights improved hand hygiene compliance from 11.8% to 20.7%, and this effect was unchanged over the 6-week study period. Fully charged lights resulted in a greater compliance increase. A preemptive sign did not have a significant effect on hand hygiene rates nor did absolute temperatures. Conclusions Flashing lights are a simple, inexpensive way of improving hand hygiene. Brighter lights appear to have a greater effect; however, this must be balanced with annoyance in specific settings. Temperature did not have a significant effect; however, this may be because the relationship does not fit a linear model. Other interventions, such as signs, may need to be tailored specifically to individual hospital environments.

BackgroundMany interventions have been implemented to improve hand hygiene compliance, each with varying effects and monetary costs. Although some previous studies have addressed the issue of conspicuousness, we found only 1 study that considered improving hand hygiene by using flashing lights.MethodOur attention theory–based hypothesis tested whether a simple red light flashing at 2-3 Hz affixed to the alcohol gel dispensers, within the main hospital entrance, would increase hand hygiene compliance over the baseline rate. Baseline and intervention observations were completed over five 60-minute periods (Monday-Friday) from 7:30 to 8:30 AM using a covert observation method.ResultsBaseline hand hygiene compliance was 12.4%. Our intervention increased compliance to 23.5% during cold weather and 27.1% during warm weather. Overall, our pooled compliance rate increased to 25.3% (P < .0001).ConclusionsA simple, inexpensive flashing red light affixed to alcohol gel dispensers was sufficiently salient to approximately double overall hand hygiene compliance within the main hospital entrance. We hypothesize that our intervention drew attention to the dispensers, which then reminded employees and visitors alike to wash their hands. Compliance was worse during cold days, presumably related to more individuals wearing gloves.

In this study, we visualized the origin of Lewis lung carcinoma metastasis after transducing tumor cells with green fluorescent protein (GFP) and transplanting them orthotopically in the middle lobe of the right lung of nude mice. Metastasis was visualized in live tissue at single cell resolution by GFP-expression as early as 18 h post-tumor transplant. At this time, single-file streaming lung carcinoma cells already had invaded inferiorly via a tubular lymphatic structure crossing the lower lobes of the lung to the ipsilateral diaphragmatic surface. By post-implantation day 2, the ipsilateral lower lobes of the lung were involved with metastatic cells. By post-implantation day 3, the ipsilateral lower lobes of the lung and the ipsilateral diaphragmatic surface were highly involved with streaming metastatic cells trafficking in single file. By day 4 post-implantation, cancer cells invaded across the diaphragm to the contralateral diaphragmatic surface. Metastatic cells then invaded superiorly through a lymphatic vessel to involve the contralateral mediastinal lymph nodes. In this model of lung cancer, the origin of metastasis was an inferior invasion from the implanted tumor via a lymphatic duct to the ipsilateral diaphragmatic surface. The cancer cells from this site invaded on the surface of the diaphragm to the contralateral diaphragmatic surface and proceeded superiorly through a lymphatic duct to contralateral lymph nodes. Other organs such as the kidneys and the adrenal glands later became involved with metastasis with the contralateral mediastinal lymph nodes as the source. The use of GFP and the highly metastatic orthotopic lung cancer model allowed the visualization of the origin of metastasis at the single-cell level and demonstrated the critical role of lymphatic ducts and the diaphragmatic surface as the path to the contralateral side.

LATS (large tumor suppressor) or warts is a Ser/Thr kinase that belongs to the Ndr/LATS subfamily of AGC (protein kinase A/PKG/PKC) kinases. It is a tumor suppressor gene originally isolated from Drosophila and recently isolated from mice and humans. Drosophila or mice mutant for LATS develop tumors in various tissues. Recent studies in Drosophila demonstrate that LATS is a central player of an emerging tumor suppressor pathway called the Hippo-LATS/Warts pathway that suppresses tumor growth by regulating cell proliferation, cell growth, and cell death. Although tremendous progress has been made toward understanding the roles of LATS in tumorigenesis, the kinase substrates of LATS or downstream target proteins mediating LATS function remain largely unknown. In this study, we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. We have also identified HX(R/H/K)XX(S/T) as the consensus phosphorylation sequence for LATS/Ndr kinase substrates. Significantly, we have discovered that LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. Finally, by using microarray analysis, we have also identified many oncogenes or tumor suppressor genes up-regulated or down-regulated by YAP. These research findings will have profound impacts on our understanding of the molecular mechanism of the LATS tumor suppressor and the emerging Hippo-LATS/Warts pathway.

A novel intra-operative chemotherapy nude mouse model for human hepatocellular carcinoma (HCC) has been developed. Intra-peritoneal (i.p.) administration of 5-fluorouracil (5-FU) was begun 2 hr before hepatic resection of HCC and then continued post-operatively for 4 consecutive days. This regime, termed intra-hepatectomy chemotherapy (IHC), significantly prolonged animal survival compared with pre-operative 5-FU, neoadjuvant therapy, 5-FU post-operative adjuvant therapy, surgery alone, 5-FU without surgery, and the untreated control. The median survival of the intra-operative 5-FU-treated group was 127 days compared with 78 days for the neoadjuvantly-treated animals and 53 days for the control group (p

Gemcitabine is a promising new agent that has been recently studied for palliation of advanced (stage IV) unresectable pancreatic cancer. We hypothesized that adjuvant gemcitabine would reduce recurrence and metastases following surgical resection of pancreatic cancer. To test this hypothesis, we evaluated gemcitabine on a green fluorescent protein (GFP) transductant of the human pancreatic cancer cell line BxPC-3 (BxPC-3-GFP) using surgical orthotopic implantation (SOI) in nude mice. GFP enabled high resolution fluorescent visualization of primary and metastatic growth. Five weeks after SOI, the mice were randomized into three groups: Group I received exploratory laparotomy only. Group II underwent surgical resection of the pancreatic tumor without further treatment. Group III underwent tumor resection followed by adjuvant treatment with gemcitabine, 100 mg/kg every three days for a total of four doses, starting two days after resection. The mice were sacrificed at thirteen weeks following implantation and the presence and location of recurrent tumor was recorded. Gemcitabine reduced the recurrence rate to 28.6% compared to 70.6% with resection only (P=0.02) and reduced metastatic events 58% in the adjuvant group compared to resection only. This study, demonstrating that gemcitabine is effective as adjuvant chemotherapy post-pancreatectomy, suggests this new indication of the drug clinically.

The Lewis lung carcinoma has been widely used for many important studies. However, the subcutaneous transplant or orthotopic cell-suspension injection models have not allowed the expression of its full metastatic potential. A powerful new highly metastatic model of the widely-used Lewis lung carcinoma is reported here using surgical orthotopic implantation (SOI) of tumor fragments and enhanced green fluorescent protein (GFP) transduction of the tumor cells. To achieve this goal, we first developed in vitro a stable high-expression GFP transductant of the Lewis lung carcinoma with the pLEIN retroviral expression vector containing the enhanced Aequorea victoria GFP gene. Stable high-level expression of GFP was found maintained in vivo in subcutaneously-growing Lewis lung tumors. The in vivo GFP-expressing tumors were harvested and implanted as tissue fragments by SOI in the right lung of additional nude mice. This model resulted in rapid orthotopic growth and extensive metastasis visualized by GFP-expression. 100% of the animals had metastases on the ipsilateral diaphragmatic surface, contralateral diaphragmatic surface, contralateral lung parenchima, and in mediastinal lymph nodes. Heart metastases were visualized in 40%, and brain metastases were visualized in 30% of the SOI animals. Mice developed signs of respiratory distress between 10–15 days post-tumor implantation and were sacrificed. The use of GFP-transduced Lewis lung carcinoma transplanted by SOI reveals for the first time the high malignancy of this tumor and provides an important useful model for metastasis, angiogenesis and therapeutic studies.

Partial hepatectomy has been widely employed in clinical practice as the therapy of choice for primary and metastatic liver tumors. However, the recurrence rate after the treatment remains high, which is most likely due to the growth of residual microscopic lesions. Previous studies in murine models demonstrated that a 70% hepatectomy significantly accelerated the growth of ectopically implanted tumors. In this study, we reported the effect of partial hepatectomy on the growth of two human colon cancers (Co-3 and AC3603) implanted in the liver of nude mice using the technique of surgical implantation of histologically intact tumor tissue. Our results showed a dramatic acceleration of tumor growth following 30% partial hepatectomy, which resembles clinical procedures. Tumor volumes were assessed with calipers on day-15 by abdominal palpation and on day-30 at autopsy by direct measurement. For both Co-3 and AC3603, tumor volumes in the hepatectomized animals were significantly larger than the control at the above two time points (P

In this study, we visualized the origin of Lewis lung carcinoma metastasis after transducing tumor cells with green fluorescent protein (GFP) and transplanting them orthotopically in the middle lobe of the right lung of nude mice. Metastasis was visualized in live tissue at single cell resolution by GFP-expression as early as 18 h post-tumor transplant. At this time, single-file streaming lung carcinoma cells already had invaded inferiorly via a tubular lymphatic structure crossing the lower lobes of the lung to the ipsilateral diaphragmatic surface. By post-implantation day 2, the ipsilateral lower lobes of the lung were involved with metastatic cells. By post-implantation day 3, the ipsilateral lower lobes of the lung and the ipsilateral diaphragmatic surface were highly involved with streaming metastatic cells trafficking in single file. By day 4 post-implantation, cancer cells invaded across the diaphragm to the contralateral diaphragmatic surface. Metastatic cells then invaded superiorly through a lymphatic vessel to involve the contralateral mediastinal lymph nodes. In this model of lung cancer, the origin of metastasis was an inferior invasion from the implanted tumor via a lymphatic duct to the ipsilateral diaphragmatic surface. The cancer cells from this site invaded on the surface of the diaphragm to the contralateral diaphragmatic surface and proceeded superiorly through a lymphatic duct to contralateral lymph nodes. Other organs such as the kidneys and the adrenal glands later became involved with metastasis with the contralateral mediastinal lymph nodes as the source. The use of GFP and the highly metastatic orthotopic lung cancer model allowed the visualization of the origin of metastasis at the single-cell level and demonstrated the critical role of lymphatic ducts and the diaphragmatic surface as the path to the contralateral side.