Preventing the Spread: A Comprehensive Cancer Center's Journey to Prevent the Spread of Coronavirus Disease (Covid-19) During the 2020 Pandemic.

BACKGROUND: On March 11, 2020, the World Health Organization (WHO) declared Coronavirus Disease (COVID-19) a pandemic. Hospitals around the world began to implement infection prevention and control (IPC) measures to stop further spread and prevent infections within their facilities. Healthcare organizations were challenged to develop response plans, procure personal protective equipment (PPE) that was in limited supply while continuing to provide quality, safe care. METHODS: As a comprehensive cancer center with immunocompromised patients, our efforts began immediately. Preventative measures were established and, as of September 2020, over 14,000 patients have been tested within the facility. From March 2020 through September 2020, only one case of hospital acquired (HA) COVID-19 was identified among our patients. Two cases of suspected community acquired (SCA) cases were also identified. Following the Centers for Disease Control (CDC) guidance, IPC measures were implemented within the facility as information science about the virus developed. This article addresses the IPC measures taken, such as enhancing isolation precautions, implementing screening protocols, disinfecting and reusing N95 respirators, by the center throughout the pandemic as well as the challenges that arouse with a new and emerging infectious disease. CONCLUSIONS: The infection control measures implemented at our comprehensive cancer center during the COVID-19 pandemic allowed our center to continue to provide world class cancer care with minimal COVID-19 infection transmission among patients and team members.

Dual antibiotic prevention bundle is associated with decreased surgical site infections.

BACKGROUND: Gynecologic oncology surgery is associated with a wide variation in surgical site infection risk. The optimal method for infection prevention in this heterogeneous population remains uncertain. STUDY DESIGN: A retrospective cohort study was performed to compare surgical site infection rates for patients undergoing hysterectomy over a 1-year period surrounding the implementation of an institutional infection prevention bundle. The bundle comprised pre-operative, intra-operative, and post-operative interventions including a dual-agent antibiotic surgical prophylaxis with cefazolin and metronidazole. Cohorts consisted of patients undergoing surgery during the 6 months prior to this intervention (pre-bundle) versus those undergoing surgery during the 6 months following the intervention (post-bundle). Secondary outcomes included length of stay, readmission rates, compliance measures, and infection microbiology. Data were compared with pre-specified one-sided exact test, Chi-square test, Fisher's exact test, or Kruskal-Wallis test as appropriate. RESULTS: A total of 358 patients were included (178 PRE, 180 POST). Median age was 58 (range 23-90) years. The post-bundle cohort had a 58% reduction in surgical site infection rate, 3.3% POST vs 7.9% PRE (-4.5%, 95% CI -9.3% to -0.2%, p=0.049) as well as reductions in organ space infection, 0.6% POST vs 4.5% PRE (-3.9%, 95% CI -7.2% to -0.7%, p=0.019), and readmission rates, 2.2% POST vs 6.7% PRE (-4.5%, 95% CI -8.7% to -0.2%, p=0.04). Gram-positive, Gram-negative, and anaerobic bacteria were all prevalent in surgical site infection cultures. There were no monomicrobial infections in post-cohort cultures (0% POST vs 58% PRE, p=0.04). No infections contained methicillin-resistant Staphylococcus aureus. CONCLUSION: Implementation of a dual antibiotic infection prevention bundle was associated with a 58% reduction in surgical site infection rate after hysterectomy in a surgically diverse gynecologic oncology practice.

Bis(benzoyl) phosphate inactivators of beta-lactamase C from Mtb.

The class A ß-lactamase BlaC is a cell surface expressed serine hydrolase of Mycobacterium tuberculosis (Mtb), one of the causative agents for Tuberculosis in humans. Mtb has demonstrated increased susceptibility to ß-lactam antibiotics upon inactivation of BlaC; thus, making BlaC a rational enzyme target for therapeutic agents. Herein, we present the synthesis and structure-activity-relationship data for the 1st-generation library of bis(benzoyl) phosphates (1-10). Substituent effects ranged from σp = -0.27 to 0.78 for electronic and π = -0.41 to 1.98 for hydrophobic parameters. Compounds 1, 4 and 5 demonstrated the greatest inhibitory potency against BlaC in a time-dependent manner (kobs = 0.212, 0.324, and 0.450 mn-1 respectively). Combined crystal structure data and mass spectrometric analysis of a tryptic digest for BlaC inactivated with 4 provided evidence that the mechanism of inactivation by this bis(benzoyl) phosphate scaffold occurs via phosphorylation of the active-site Ser-70, ultimately leading to an aged form of the enzyme.

Artificial Differences in Clostridium difficile Infection Rates Associated with Disparity in Testing.

In 2015, Clostridium difficile testing rates among 30 US community, multispecialty, and cancer hospitals were 14.0, 16.3, and 33.9/1,000 patient-days, respectively. Pooled hospital onset rates were 0.56, 0.84, and 1.57/1,000 patient-days, respectively. Higher testing rates may artificially inflate reported rates of C. difficile infection. C. difficile surveillance should consider testing frequency.

Therapist Use of Specific and Nonspecific Strategies Across Two Affect-Focused Psychotherapies for Depression: Role of Adherence Monitoring.

Psychotherapists routinely use both specific and non-specific strategies to deliver empirically supported treatments (ESTs). Psychotherapy adherence monitoring has traditionally focused on assessing therapist use of EST-specific strategies (to distinguish between ESTs), paying less attention to non-specific techniques common to multiple psychotherapies. This study used the Collaborative Study Psychotherapy Rating Scale (CSPRS) to evaluate therapist use of both specific and non-specific techniques in two affect-focused ESTs for depression. Blinded raters evaluated 180 recorded sessions of interpersonal psychotherapy (IPT) and brief supportive psychotherapy (BSP). Because IPT and BSP both emphasize attention to affective states and developing a warm therapy relationship, we expected overlap across scales measuring therapist warmth, empathy, and focus on feelings. In contrast, we expected differences in scales measuring therapist directiveness, as well as IPT- and BST-specific interventions. Results showed raters displayed good inter-rater reliability on primary subscales and could discriminate between two treatments with considerable overlap. Both IPT and BSP therapists used similarly high levels of non-specific, facilitative interventions. Expectedly, IPT therapists were more directive and used more IPT-specific strategies, while BSP therapists utilized more non-directive, supportive strategies. Unexpectedly, BSP therapists showed greater focus on feelings than IPT therapists. Exploratory analyses suggested that greater focus on feelings in early sessions was associated with greater depressive symptom reduction in the first eight weeks of treatment for both ESTs. Additional treatment adherence research is needed to investigate both shared and distinctive features of ESTs, as well as the effect of the relative use of specific versus non-specific interventions on psychotherapy outcomes.

A Retrospective Comparison of Home Telehealth and Nursing Care With or Without Rehabilitation Therapy on Rehospitalization Rates of Individuals With Heart Failure.

PURPOSE: Congestive heart failure (CHF) is the most common reason for rehospitalization among the aging population, accounting for one-fifth of all hospital admissions. To date, there is no research comparing the rehospitalization rates between patients with CHF (PWCHF) who receive telehealth and home health nursing care versus a multidisciplinary team consisting of telehealth, home nursing, physical therapy (PT), and/or occupational therapy (OT). METHODS: A retrospective analysis was performed with 132 Medicare Part A home health patients discharged from an inpatient setting with a primary or secondary diagnosis of CHF receiving daily telehealth over the course of 1 year. Allscripts Home Care and Lifestream software was used to query data from patient records. Rehospitalization rates were analyzed using Cochran-Mantel-Haenszel tests. Patients were divided into 3 groups: (1) nursing only; (2) nursing and PT or OT; or (3) nursing, PT, and OT. RESULTS: A total of 41 of the 132 patients (31.06%) were rehospitalized during their home health 60-day episode of care. This percentage includes all-cause rehospitalizations. Cochran-Mantel-Haenszel tests indicated there were no differences in rehospitalization rates between the 3 groups after controlling for the confounding variables: (1) multiple hospitalizations (P = .15); (2) history of falls (P = .16); or (3) depression (P = .18). CONCLUSIONS: There was no statistically significant difference between the 3 groups for all-cause rehospitalization rates. Further prospective research is required to determine best practices and multidisciplinary protocols to further reduce rehospitalization rates in this population.

Brief Psychotherapy for Maternal Depression: Impact on Mothers and Children.

OBJECTIVE: Two-generation studies demonstrate that treating maternal depression benefits school-age children. Although mothers prefer psychotherapy to medication, little is known about how psychotherapy for maternal depression affects offspring, especially in very high-risk families in which both mothers and children concurrently meet syndromal criteria for psychiatric disorders. This trial evaluated the effects of 2 brief psychotherapies for maternal depression on very high-risk families. METHOD: Mothers with major depressive disorder were randomly assigned to 9 sessions of either brief interpersonal psychotherapy for mothers (IPT-MOMS; n = 85) or brief supportive psychotherapy (BSP; n = 83). Independent assessors evaluated mothers and their children, ages 7 to 18 years, diagnosed with at least 1 internalizing disorder, every 3 months over the course of 1 year. RESULTS: Symptoms and functioning of mothers and children improved significantly over time, with no between-group differences. However, children of mothers assigned to BSP had more outpatient mental health visits and were more likely to receive antidepressant medication. Mothers reported greater satisfaction with IPT-MOMS than BSP. Improvement in mothers' depressive symptoms was associated with improvement in child functioning in time-lagged fashion, with children improving 3 to 6 months after mothers improved. Antidepressant medication use and number of mental health visits received by children did not affect outcomes. CONCLUSION: IPT-MOMS and BSP demonstrated comparable beneficial effects on maternal depression. Children's functioning improved following maternal improvement, independent of youths' treatment. Children of mothers randomized to IPT-MOMS, compared with BSP, achieved comparable outcomes despite less follow-up treatment. Observation of lagged association between maternal improvement and change in child functioning should influence treatment planning for families. Clinical trial registration information-Psychotherapy for Depressed Mothers of Psychiatrically Ill Children; http://clinicaltrials.gov/; NCT00919594.

Development of inhibitor-directed enzyme prodrug therapy (IDEPT) for prostate cancer.

Prostate cancer (PCa) is the second most common cause of cancer death among American men after lung cancer. Unfortunately, current therapies do not provide effective treatments for patients with advanced, metastatic, or hormone refractory disease. Therefore, we seek to generate therapeutic agents for a novel PCa treatment strategy by delivering a suicide enzyme (yCDtriple) to a cell membrane bound biomarker found on PCa cells (prostate-specific membrane antigen (PSMA)). This approach has resulted in a new PCa treatment strategy reported here as inhibitor-directed enzyme prodrug therapy (IDEPT). The therapeutic agents described were generated using a click chemistry reaction between the unnatural amino acid (p-azidophenylalanine (pAzF)) incorporated into yCDtriple and the dibenzylcyclooctyne moiety of our PSMA targeting agent (DBCO-PEG4-AH2-TG97). After characterization of the therapeutic agents, we demonstrate significant PCa cell killing of PSMA-positive cells. Importantly, we demonstrate that this click chemistry approach can be used to efficiently couple a therapeutic protein to a targeting agent and may be applicable to the ablation of other types of cancers and/or malignancies.

Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated endoscopic equipment.

Klebsiella producing carbapenemase is an emerging pathogen. We report transmission of this organism by contaminated endoscopic instruments. Quick identification of source, staff education, contact precautions, and emphasis on hand and environmental hygiene led to case control and prevention of outbreak.

Hospital-onset Clostridium difficile infection rates in persons with cancer or hematopoietic stem cell transplant: a C3IC network report.

A multicenter survey of 11 cancer centers was performed to determine the rate of hospital-onset Clostridium difficile infection (HO-CDI) and surveillance practices. Pooled rates of HO-CDI in patients with cancer were twice the rates reported for all US patients (15.8 vs 7.4 per 10,000 patient-days). Rates were elevated regardless of diagnostic test used.

Keratoconjunctivitis sicca associated with administration of etodolac in dogs: 211 cases (1992-2002).

OBJECTIVE: To characterize features and response to treatment of keratoconjunctivitis sicca (KCS) associated with oral administration of etodolac in dogs. DESIGN: Retrospective case series. SAMPLE POPULATION: 65 cases obtained from a survey of veterinary ophthalmologists (group A) and 146 cases reported to Fort Dodge Animal Health (group B). PROCEDURES: Data analyzed included breed, sex, age, weight, dose and duration of etodolac administration, results of Schirmer tear test at the time of diagnosis and last follow-up, treatments, and response to treatments. Groups A and B were analyzed separately by use of forward stepwise logistic regression models developed to predict probability of complete remission or clinical improvement as a function of several variables. RESULTS: Most dogs developed severe KCS (84 eyes of 50 dogs [group A]; 111 eyes of 62 dogs [group B]). Resolution of KCS occurred in 7 of 65 (A) and 23 of 146 (B) dogs. No response to treatment was observed in 26 of 65 (A) and 27 of 146 (B) dogs. Fifty-one (A) and 52 (B) dogs had records that were sufficiently complete to use in models. In group B, dogs with etodolac treatment intervals < 6 months prior to the onset of KCS were 4.2 times as likely to have remission as were dogs with treatment intervals > or = 6 months. CONCLUSIONS AND CLINICAL RELEVANCE: Shorter duration of etodolac administration (< 6 months) was associated with improved outcome in 1 population of dogs. Monitoring of tear production should be considered prior to and during administration of etodolac in dogs.

Polydnavirus genes that enhance the baculovirus expression vector system.

The baculovirus expression vector system (BEVS) is a powerful and versatile system for protein expression, which has many advantages. However, a limitation of any lytic viral expression system, including BEVS, is that death and lysis of infected insect cells terminates protein production. This results in interruption of protein production and higher production costs due to the need to set up new infections, maintain uninfected cells, and produce pure viral stocks. Genetic methods to slow or prevent cell death while maintaining high-level, virus-driven protein production could dramatically increase protein yields. Several approaches have been used to improve the BEVS and increase the synthesis of functional proteins. Successful enhancement of the BEVS was obtained when various gene elements were added to the virus, secretion and posttranslational processing were modified, or protein integrity was improved. A gene family from the insect virus Campoletis sonorensis ichnovirus (CsIV) was discovered that delays lysis of baculovirus-infected cells, thereby significantly enhancing recombinant protein production in the BEVS system. By using the CsIV vankyrin gene family, protein production in the vankyrin-enhanced BEVS (VE-BEVS) was increased by a factor of 4- to 15-fold by either coexpressing the vankyrin protein from a dual BEVS or by providing its activity in trans by expressing the vankyrin protein from a stably transformed cell line. In sum, VE-BEVS is an enhancement of the existing BEVS technology that markedly improves protein expression levels while reducing the cost of labor and materials.

Effect of Campoletis sonorensis ichnovirus cys-motif proteins on Heliothis virescens larval development.

Polydnaviruses are obligate symbionts of some parasitic hymenopteran wasps responsible for modifying the physiology of their host lepidopteran larvae to benefit the endoparasite. Injection of Campoletis sonorensis ichnovirus (CsIV) into Heliothis virescens larvae alters larval growth, development and immunity but genes responsible for alterations of host physiology are not well described. Recent studies of polydnavirus genomes establish that these genomes encode families of related genes expressed in parasitized larvae. Here we evaluate five members of the CsIV cys-motif gene family for their ability to inhibit growth and development of lepidopteran larvae. To study the function of cys-motif proteins, recombinant proteins were produced from baculovirus expression vectors and injected or fed to H. virescens larvae in diet. rVHv1.1 was identified as the most potent protein tested causing a significant reduction in growth of H. virescens and Spodoptera exigua larvae. H. virescens larvae ingesting this protein also exhibited delayed development, reductions in pupation and increased mortality. Increased mortality was associated with chronic sub-lethal baculovirus infections. Taken together, these data indicate that the cys-motif proteins have pleiotropic effects on lepidopteran physiology affecting both development and immunity.

Quantitative analysis of hemocyte morphological abnormalities associated with Campoletis sonorensis parasitization.

Endoparasitoids of arthropods evoke host cellular immune responses that result in hemocytic encapsulation of the endoparasitoid, unless these responses are disrupted by the parasite. Our interest has focused on mutualistic viruses found in some hymenopteran endoparasitoids that disrupt hemocyte function and prevent encapsulation. Specifically, the Campoletis sonorensis polydnavirus interacts with wasp factors to suppress immunity via expression of intracellular and secreted viral proteins. To study the roles of specific parasitization-associated factors on immunocyte morphology, fluorescence microscopy was used to visualize the actin cytoskeleton in infected and uninfected cells, or after treatment with C. sonorensis ovarian proteins or plasma from infected larvae. The titer and distribution of F- and G-actin were altered in hemocytes from parasitized insects relative to control cells, with plasma from parasitized larvae having an intermediate effect. This suggests that intracellular and secreted factors contribute to suppression of cellular immune responses in C. sonorensis.