A review of the novel tissue factor antibody-drug conjugate: Tisotumab vedotin.

OBJECTIVE: To review and compare the pharmacology, efficacy, and safety of the novel tissue factor antibody-drug conjugate, tisotumab vedotin. DATA SOURCES: Literature search was performed through PubMed MEDLINE, Google Scholar, ClinicalTrials.gov, and the Food and Drug Administration. DATA SUMMARY: Tisotumab vedotin, a novel tissue factor antibody-drug conjugate, was granted accelerated approval by the US FDA on 20 September 2021 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Tisotumab vedotin demonstrated clinical efficacy in a number of solid tumors in innovaTV 201 and more specifically in cervical cancer in the pivotal phase 2 innovaTV 204. In the single-arm innovaTV 204 study, 101 patients with recurrent or metastatic cervical cancer received intravenous tisotumab vedotin at the recommended dose of 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The independent review committee confirmed an objective response rate of 24% with 7% complete responses and 17% partial responses. Tisotumab vedotin is associated with several notable adverse events with data from innovaTV 204 including ocular toxicity, hemorrhage, and peripheral neuropathy. Ninety-two percent of patients experienced treatment-related adverse events with 28% experiencing an adverse event of grade 3 or higher. CONCLUSIONS: Metastatic cervical cancer has a high risk of relapse with few effective second-line therapeutic options. Current guidelines recommend single agent tisotumab vedotin as a possible option. Ongoing trials will further define its place in therapy.

Impact of pharmacist-managed immune checkpoint inhibitor toxicities.

BACKGROUND: Immune checkpoint inhibitors are associated with unique autoimmune side effects that differ from traditional cytotoxic chemotherapy. Pharmacists may play an important role in providing key supportive care measures necessary to aid patients and oncologists through immune-related adverse events (irAEs). This study aims to evaluate the impact of a pharmacist-managed irAE protocol in an oncology clinic. METHODS: This study is a retrospective chart review of the implementation of a pilot irAE pharmacy protocol. Patients treated with an immune checkpoint inhibitor and subsequently identified to have dermatologic, gastrointestinal, hepatic, or thyroid toxicities and managed under the pilot irAE pharmacy protocol from 1 October 2018 to 28 February 2019 were enrolled. Study endpoints included number of pharmacist interventions and physician satisfaction. Additional endpoints included pharmacotherapy initiated, dose adjustments, and patient follow-ups. RESULTS: From 1 October 2018, to 28 February 2019, 17 patients were referred and approved by their primary oncologists for pharmacy management under the pilot irAE protocol. During the pilot period, pharmacists initiated 21 new medications for the treatment of irAEs, including thyroid hormone replacement in 7 patients (41%) and oral corticosteroids in 6 patients (35%) with a total of 28 dose adjustments. In addition, the pilot protocol included an assessment of physician satisfaction, which showed a reduced number of physician hours per month managing irAEs, increased physician confidence in irAE management, and a desire for continued pharmacist-management of irAEs. CONCLUSIONS: Oncology pharmacists had an impact on management of toxicities in our oncology clinic as indicated by the pharmacist interventions and physician satisfaction.

Risk Factors for Bed Bugs Among Urban Emergency Department Patients.

Bed bugs are a significant and under-studied public health nuisance. We surveyed 706 emergency department patients and found bed bug infestations were more likely (p < 0.05) among subjects having persons 19-64 years of age in the house, living in a group home, a previous history with bed bugs, and knowing someone who currently has bed bugs. Sleeping in a hotel, recent homelessness, obtaining used clothing or furniture and using a laundromat were not associated with increased risk (p > 0.05) for infestation. Individuals with less education and income were more likely (p < 0.05) to have bed bugs and express concern about getting bed bugs. Younger persons were more likely to correctly identify a picture of a bed bug compared to those over the age of 60 years (p < 0.001).

Destabilized reporters for background-subtracted, chemically-gated, and multiplexed deep-tissue imaging.

Tracking gene expression in deep tissues requires genetic reporters that can be unambiguously detected using tissue penetrant techniques. Magnetic resonance imaging (MRI) is uniquely suited for this purpose; however, there is a dearth of reporters that can be reliably linked to gene expression with minimal interference from background tissue signals. Here, we present a conceptually new method for generating background-subtracted, drug-gated, multiplex images of gene expression using MRI. Specifically, we engineered chemically erasable reporters consisting of a water channel, aquaporin-1, fused to destabilizing domains, which are stabilized by binding to cell-permeable small-molecule ligands. We showed that this approach allows for highly specific detection of gene expression through differential imaging. In addition, by engineering destabilized aquaporin-1 variants with orthogonal ligand requirements, it is possible to distinguish distinct subpopulations of cells in mixed cultures. Finally, we demonstrated this approach in a mouse tumor model through differential imaging of gene expression with minimal background.

Severity of injury and the decision to arrest in cases of intimate partner violence.

From a victim's physical health perspective, at the centre of any case of intimate partner violence (IPV) is the degree of trauma imparted on that victim by the offender. Yet, the implementations of state-level 'Mandatory Arrest' and 'Preferred Arrest' laws encourage arrests decisions in cases of IPV typically without regard to the level of trauma severity found in each case. And, despite these well-meaning implementations and the gravity of their consequences, the importance of evaluating trauma severity in victims of IPV remains largely overlooked. The goal of this study was to correlate police arrest decisions in cases of IPV to a trauma severity score generated from established clinical protocols in the treatment of trauma. A Trauma Severity Quantification Table (TSQT) was created in order to quantify the major factors of an incident of IPV: anatomical location of attack, method of attack, facilitating weapon/object and resulting trauma. A total of 256 cases of IPV reported to six police departments in Idaho, a state with a discretionary arrest law in domestic violence cases, in the calendar year 2000 were processed using the TSQT. A statistically significant difference was found between arrests (mean 17.96, standard deviation [SD] 5.90) versus no arrest (mean 16.13, SD 5.67) outcomes (P = 0.03). It is suggested that trauma severity is a factor in police arrest decisions in a discretionary state sample, but that more attention needs to be brought to this method of analysis and its implications for future arrest decisions.

Emergency Medical Services Provider Self-Reported Occupational Safety.

BACKGROUND: Emergency medical services (EMS) providers are at high risk for occupational violence, and some tactical EMS providers carry weapons. METHODS: Anonymous surveys were administered to tactical and nontactical prehospital providers at 180 prehospital agencies in northeast Ohio between September 2018 and March 2019. Demographics were collected, and survey questions asked about workplace violence and comfort level with tactical EMS carrying weapons. RESULTS: Of 432 respondents, 404 EMS providers (94%) reported a history of verbal or physical assault on scene, and 395 (91%) reported working in a setting with a direct active threat at least rarely. Of those reporting a history of assault on scene, 46.5% reported that it occurred at least sometimes. Higher rates of assault on scene were associated with being younger, white, or an emergency medical technician-paramedic, working in an urban environment, having more frequent direct active threats, and having more comfort with tactical EMS carrying firearms (p ≤ .03). Most respondents (306; 71%) reported that they were prepared to defend themselves from someone who originally called for help. Most (303; 70%) reported a comfort level of 8 or higher (from 1, not comfortable to 10, completely comfortable) with tactical EMS providers carrying weapons. Comfort with tactical EMS providers carrying weapons was associated with being white, not having a bachelor's degree, and feeling prepared to defend oneself from a patient (p ≤ .02). CONCLUSION: EMS providers in the survey report high rates of verbal and physical violence while on scene and are comfortable with tactical EMS providers carrying weapons.

Knowledge, Experience, and Concerns Regarding Bed Bugs Among Emergency Medical Service Providers.

Introduction Bed bugs are commonly encountered by emergency medical service (EMS) providers. The objective of this study was to determine the frequency with which EMS providers encountered bed bugs, assess their knowledge about bed bugs, and analyze the actions they take after finding bed bugs. Methods We anonymously surveyed 407 EMS providers from 180 EMS agencies in northeast Ohio between September 1, 2018, through March 31, 2019. Results Among the providers surveyed, 21% (n = 84) of the EMS providers reported seeing bed bugs at least monthly, and 6% (n = 24) reported seeing bed bugs at least weekly. Being younger, male, and working in an urban environment (vs. rural) were associated with EMS providers reporting more frequent bed bug encounters (p: ≤.05). The mean level of concern for encountering bed bugs among EMS providers was 3.54 (SD: 1.15; scale: 1 = no concern, 5 = very concerned). Among the EMS providers who reported seeing bed bugs at least monthly, 30% took the affected EMS stretcher out of service when they encounter a bed bug, 43% took the EMS rig out of service, 83% cleaned the EMS stretcher with a disinfectant, and 88% notified the ED that their patient has bed bugs. EMS providers scored poorly (mean: 69% correct responses) in a seven-question assessment of basic bed bug biology and public health. Conclusion Based on our findings, we concluded that EMS knowledge and behavior related to bed bugs are suboptimal.

Cimicosis in Persons Previously Fed Upon by Bed Bugs.

Introduction Bed bug infestations have risen dramatically in many industrialized nations in recent decades. Most people fed upon by bed bugs will develop a pruritic rash although the frequency with which this occurs is not definitively known and may depend on host factors including the duration of the infestation. Methods Surveys were completed from 706 emergency department (ED) patients in Cleveland, OH about their current and past exposure with bed bugs. Subjects were asked about any post-bed bug feeding rashes that developed. Results There were 24% (169/698) of subjects reporting either a current or past home bed bug infestation, with 37% (253/698) reporting they had previously been fed upon by a bed bug. Of those reporting a previous bed bug feeding, 68% (172/253) reported a pruritic post-bed bug feeding rash and 24% (57/237) reported developing a blister. Overall, 5% (37/705) of ED patients reported currently having a rash, but only 2% (14/698) of ED patients reported currently have bed bugs at home and of those, only 14% (2/14) said they currently had a rash. Conclusion While 68% of ED patients reported a pruritic post-bed bug feeding pruritic rash, almost a third of persons did not report developing the rash. Post-bed bug feeding blister reactions are less common. Asking ED patients about a rash had a low sensitivity of 14% (2-43%) and a specificity 95% (93-96%) to identify persons reporting home bed bugs.

Characteristics of Bed Bug Infested Patients in the Emergency Department.

Cimex lectularius L., the common bed bug, is a hematophagous human ectoparasite that has undergone a global resurgence in the past two decades. We surveyed 706 active emergency department (ED) patients about their experiences with bed bugs. We found that 2% of ED patients reported having a current bed bug infestation, significantly more than the historical number of ED patients upon which we find bed bug; 37% of ED patients report previously having been fed on by a bed bug; 15% currently know someone with an active infestation; and 59% know someone that has had an infestation within ≤ 5 years. Only 18% of bed bug infested patients reported their infestation to emergency medicine providers and only 21% were put in isolation precautions. We found that 25% of patients with bed bugs worried about receiving worse healthcare because of their infestation. Persons with bed bugs were more likely compared to those without bed bugs to be older (52 vs. 41 years) and arrive by ambulance (57% vs. 14%) (p < 0.05), but not reporting insomnia (50% vs. 49%) (p = 1.0). Bed bug infested patients can be common in the ED. Most bed bug infested patients are older, arrive to the ED by ambulance, do not report their infestation to healthcare providers, and are not adequately placed into isolation precautions, potentially putting other patients and providers at risk for acquiring the infestation.

Genetic engineering of Francisella tularensis LVS for use as a novel live vaccine platform against Pseudomonas aeruginosa infections.

Francisella tularensis LVS (Live Vaccine Strain) is an attenuated bacterium that has been used as a live vaccine. Patients immunized with this organism show a very long-term memory response (over 30 years post vaccination) evidenced by the presence of indicators of robust cell-mediated immunity. Because F. tularensis LVS is such a potent vaccine, we hypothesized that this organism would be an effective vaccine platform. First, we sought to determine if we could genetically modify this strain to produce protective antigens of a heterologous pathogen. Currently, there is not a licensed vaccine against the important opportunistic bacterial pathogen, Pseudomonas aeruginosa. Because many P. aeruginosa strains are also drug resistant, the need for effective vaccines is magnified. Here, F. tularensis LVS was genetically modified to express surface proteins PilAPa, OprFPa, and FliCPa of P. aeruginosa. Immunization of mice with LVS expressing the recombinant FliCPa led to a significant production of antibodies specific for P. aeruginosa. However, mice that had been immunized with LVS expressing PilAPa or OprFPa did not produce high levels of antibodies specific for P. aerugionsa. Therefore, the recombinant LVS strain engineered to produce FliCPa may be able to provide immune protection against a P. aeruginosa challenge. However for future use of this vaccine platform, selection of the appropriate recombinant antigen is critical as not all recombinant antigens expressed in this strain were immunogenic.