ABSTRACT
In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.
Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Adult , United States/epidemiology , Humans , Adolescent , Influenza, Human/epidemiology , COVID-19 Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination , HospitalizationABSTRACT
In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , Adolescent , COVID-19/epidemiology , COVID-19/prevention & control , Advisory Committees , Emergency Service, Hospital , HospitalizationABSTRACT
BACKGROUND: The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute coronavirus disease 2019 (COVID-19) and may affect clinical management. METHODS: In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10 223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched patients with COVID-19, those with MIS-A were more likely to be non-Hispanic black and less likely to be non-Hispanic white. They more likely had laboratory-confirmed COVID-19 ≥14 days before hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, patients with MIS-A had higher neutrophil-to-lymphocyte ratio and higher levels of C-reactive protein, ferritin, procalcitonin, and D-dimer than patients with COVID-19. They also had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. The mortality rate was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management.
Subject(s)
COVID-19 , Connective Tissue Diseases , Humans , Adult , United States/epidemiology , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiologyABSTRACT
BACKGROUND: In 2020, at the onset of the COVID-19 pandemic, the United States experienced surges in healthcare needs, which challenged capacity throughout the healthcare system. Stay-at-home orders in many jurisdictions, cancellation of elective procedures, and closures of outpatient medical offices disrupted patient access to care. To inform symptomatic persons about when to seek care and potentially help alleviate the burden on the healthcare system, Centers for Disease Control and Prevention (CDC) and partners developed the CDC Coronavirus Self-Checker ("Self-Checker"). This interactive tool assists individuals seeking information about COVID-19 to determine the appropriate level of care by asking demographic, clinical, and nonclinical questions during an online "conversation." OBJECTIVE: This paper describes user characteristics, trends in use, and recommendations delivered by the Self-Checker between March 23, 2020, and April 19, 2021, for pursuing appropriate levels of medical care depending on the severity of user symptoms. METHODS: User characteristics and trends in completed conversations that resulted in a care message were analyzed. Care messages delivered by the Self-Checker were manually classified into three overarching conversation themes: (1) seek care immediately; (2) take no action, or stay home and self-monitor; and (3) conversation redirected. Trends in 7-day averages of conversations and COVID-19 cases were examined with development and marketing milestones that potentially impacted Self-Checker user engagement. RESULTS: Among 16,718,667 completed conversations, the Self-Checker delivered recommendations for 69.27% (n=11,580,738) of all conversations to "take no action, or stay home and self-monitor"; 28.8% (n=4,822,138) of conversations to "seek care immediately"; and 1.89% (n=315,791) of conversations were redirected to other resources without providing any care advice. Among 6.8 million conversations initiated for self-reported sick individuals without life-threatening symptoms, 59.21% resulted in a recommendation to "take no action, or stay home and self-monitor." Nearly all individuals (99.8%) who were not sick were also advised to "take no action, or stay home and self-monitor." CONCLUSIONS: The majority of Self-Checker conversations resulted in advice to take no action, or stay home and self-monitor. This guidance may have reduced patient volume on the medical system; however, future studies evaluating patients' satisfaction, intention to follow the care advice received, course of action, and care modality pursued could clarify the impact of the Self-Checker and similar tools during future public health emergencies.
Subject(s)
COVID-19 , Humans , United States , Pandemics , Communication , Patient Satisfaction , Centers for Disease Control and Prevention, U.S.ABSTRACT
BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel severe postinfectious condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The purpose of this report is to describe nationwide trends in the evolving clinical management of MIS-C. METHODS: Patients with MIS-C were reported from state and local jurisdictions to the Centers for Disease Control and Prevention's (CDC's) MIS-C national surveillance system. Patients' case reports were reviewed to ensure that they met the CDC MIS-C case definition and had sufficient data for analysis. The prevalence of use of treatments for MIS-C, temporal trends in use of these treatments, and frequency of administration of different treatment combinations were analyzed. RESULTS: There were 4470 patients meeting the MIS-C case definition with onset dates from 19 February 2020 to 31 July 2021. The proportion of patients admitted to an intensive care unit (ICU) has declined over time, from 78.7% in April 2020 to 57.5% in June 2021 (Pâ =â .001). The most common treatments were intravenous immunoglobulin (IVIG), given to 85.6% of patients; steroids (77.7%), and antiplatelet medications (73.7%); use of each of these treatments has increased over time, particularly in patients not requiring admission to an ICU (all Pâ <â .001). Older patients and non-Hispanic Black patients were more likely to receive additional modes of therapy including vasoactive medication, noninvasive respiratory support, anticoagulation medication, and intubation/mechanical ventilation. CONCLUSIONS: IVIG, steroids, and antiplatelet medication have become increasingly utilized as standard treatment for MIS-C patients, while the use of other treatments may be contingent on the type and severity of clinical findings.
Subject(s)
COVID-19 , Anticoagulants , COVID-19/complications , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/epidemiology , United States/epidemiologyABSTRACT
Telehealth is the use of electronic information and telecommunication technologies to provide care when the patient and the provider are not in the same room at the same time. Telehealth accounted for less than 1% of all Medicare Fee-for-Service outpatient visits in the United States in 2019 but grew to account for 46% of all visits in April 2020. Changes in reimbursement and licensure policies during the COVID-19 pandemic appeared to greatly facilitate this increased use. Telehealth will continue to account for a substantial portion of care provided in the United States and globally. A better understanding of telehealth approaches and their evidence base by public health practitioners may help improve their ability to collaborate with health care organizations to improve population health. The article summarizes the Centers for Disease Control and Prevention's (CDC's) approach to understanding the evidence base for telehealth in public health practice, possible applications for telehealth in public health practice, and CDC's use of telehealth to improve population health.
Subject(s)
COVID-19 , Telemedicine , Aged , COVID-19/epidemiology , Humans , Medicare , Pandemics , Public Health Practice , United States/epidemiologyABSTRACT
We analyzed multisystem inflammatory syndrome in children cases by reported COVID-19 vaccination status (2-dose primary series vs. no vaccination). A total of 46% vaccinated versus 58% unvaccinated persons received intensive care unit-level care ( P = 0.02); the risk of intensive care unit admission was 23% higher (adjusted relative risk: 1.23; 95% confidence interval: 1.03-1.48) among unvaccinated patients; 21 unvaccinated persons died. Multisystem inflammatory syndrome in children occurs after SARS-CoV-2 infection in vaccinated persons, but may be less severe.
Subject(s)
COVID-19 Vaccines , COVID-19 , Child , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: Clinical management of multisystem inflammatory syndrome in children (MIS-C) has varied over time and by medical institution. METHODS: Data on patients with MIS-C were collected from 4 children's hospitals between March 16, 2020 and March 10, 2021. Relationships between MIS-C treatments and patient demographics, clinical characteristics, and outcomes were described. Propensity score matching was utilized to assess the relative risk of outcomes dependent on early treatment with intravenous immunoglobulin (IVIG) or low-dose steroids, controlling for potential confounding variables. RESULTS: Of 233 patients diagnosed with MIS-C, the most commonly administered treatments were steroids (88.4%), aspirin (81.1%), IVIG (77.7%) and anticoagulants (71.2%). Compared with those patients without respiratory features, patients with respiratory features were less likely to receive IVIG and steroids on the same day (combination treatment) (44.1%). Controlling for confounding variables, patients receiving IVIG within 1 day of hospitalization were less likely to have hospital length of stay ≥8 days (RR = 0.53, 95% CI: 0.31-0.88). Patients receiving low-dose steroids within 1 day of hospitalization were less likely to develop ventricular dysfunction (RR = 0.45, 95% CI: 0.26-0.77), have increasingly elevated troponin levels (RR = 0.55, 95% CI: 0.40-0.75) or have hospital length of stay ≥8 days (RR = 0.46, 95% CI: 0.29-0.74). CONCLUSION: Treatments for MIS-C differed by hospital, patient characteristics and illness severity. When IVIG and low-dose steroids were administered in combination or low-dose steroids were administered alone within 1 day of hospitalization, the risk of subsequent severe outcomes was decreased.
Subject(s)
COVID-19 , Immunoglobulins, Intravenous , Humans , Child , United States/epidemiology , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/epidemiology , Steroids/therapeutic use , HospitalsABSTRACT
BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a multiorgan hyperinflammatory condition following SARS-CoV-2 infection. Data on COVID-19 vaccine adverse events and vaccine attitudes in children with prior MIS-C are limited. We described characteristics associated with COVID-19 vaccination, vaccine adverse events and vaccine attitudes in children with a history of MIS-C or COVID-19 and their parents/guardians. METHODS: We enrolled children previously hospitalized for MIS-C or COVID-19 from 3 academic institutions. We abstracted charts and interviewed children and parents/guardians regarding vaccine adverse events and acceptability. RESULTS: Of 163 vaccine-eligible children enrolled with a history of MIS-C and 70 with history of COVID-19, 51 (31%) and 34 (49%), respectively, received mRNA COVID-19 vaccine a median of 10 (Interquartile Range 6-13) months after hospital discharge. Among 20 children with MIS-C and parents/guardians who provided interviews, local injection site reaction of brief duration (mean 1.8 days) was most commonly reported; no children required medical care within 2 weeks postvaccination. Vaccine survey results of interviewed, vaccinated children and their parents/guardians: of 20 children with MIS-C and 15 children with COVID-19, 17 (85%) and 13 (87%), respectively, listed doctors in the top 3 most trusted sources for vaccine information; 13 (65%) and 9 (60%) discussed vaccination with their doctor. CONCLUSIONS: COVID-19 vaccination was well tolerated in children with prior MIS-C or COVID-19 participating in our investigation. Parents/guardians regarded their children's doctors as a trusted source of information for COVID-19 vaccines, and most vaccinated children's parents/guardians had discussed COVID-19 vaccination for their child with their doctor.
Subject(s)
COVID-19 , Vaccines , Humans , COVID-19 Vaccines , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Hospitalization , Vaccination , ParentsABSTRACT
BACKGROUND: The US public health response to the COVID-19 pandemic has required contact tracing and symptom monitoring at an unprecedented scale. The US Centers for Disease Control and Prevention and several partners created the Text Illness Monitoring (TIM) platform in 2015 to assist US public health jurisdictions with symptom monitoring for potential novel influenza virus outbreaks. Since May 2020, 142 federal, state, and local public health agencies have deployed TIM for COVID-19 symptom monitoring. OBJECTIVE: The aim of this study was to evaluate the utility, benefits, and challenges of TIM to help guide decision-making for improvements and expansion to support future public health emergency response efforts. METHODS: We conducted a brief online survey of previous and current TIM administrative users (admin users) from November 28 through December 21, 2020. Closed- and open-ended questions inquired about the onboarding process, decision to use TIM, groups monitored with TIM, comparison of TIM to other symptom monitoring systems, technical challenges and satisfaction with TIM, and user support. A total of 1479 admin users were invited to participate. RESULTS: A total of 97 admin users from 43 agencies responded to the survey. Most admin users represented the Indian Health Service (35/97, 36%), state health departments (26/97, 27%), and local or county health departments (18/97, 19%), and almost all were current users of TIM (85/94, 90%). Among the 43 agencies represented, 11 (26%) used TIM for monitoring staff exclusively, 13 (30%) monitored community members exclusively, and 19 (44%) monitored both staff and community members. Agencies most frequently used TIM to monitor symptom development in contacts of cases among community members (28/43, 65%), followed by symptom development among staff (27/43, 63%) and among staff contacts of cases (24/43, 56%). Agencies also reported using TIM to monitor patients with COVID-19 for the worsening of symptoms among staff (21/43, 49%) and community members (18/43, 42%). When asked to compare TIM to previous monitoring systems, 78% (40/51) of respondents rated TIM more favorably than their previous monitoring system, 20% (10/51) said there was no difference, and 2% (1/51) rated the previous monitoring system more favorably than TIM. Most respondents found TIM favorable in terms of time burden, staff burden, timeliness of the data, and the ability to monitor large population sizes. TIM compared negatively to other systems in terms of effort to enroll participants (ie, persons TIM monitors) and accuracy of the data. Most respondents (76/85, 89%) reported that they would highly or somewhat recommend TIM to others for symptom monitoring. CONCLUSIONS: This evaluation of TIM showed that agencies used TIM for a variety of purposes and rated TIM favorably compared to previously used monitoring systems. We also identified opportunities to improve TIM; for example, enhancing the flexibility of alert deliveries would better meet admin users' varying needs. We also suggest continuous program evaluation practices to assess and respond to implementation gaps.
Subject(s)
COVID-19 , Cross-Sectional Studies , Humans , Pandemics , Public Health , SARS-CoV-2 , Surveys and QuestionnairesABSTRACT
OBJECTIVE: In 2020, the COVID-19 pandemic overburdened the US health care system because of extended and unprecedented patient surges and supply shortages in hospitals. We investigated the extent to which several US hospitals experienced emergency department (ED) and intensive care unit (ICU) overcrowding and ventilator shortages during the COVID-19 pandemic. METHODS: We analyzed Health Pulse data to assess the extent to which US hospitals reported alerts when experiencing ED overcrowding, ICU overcrowding, and ventilator shortages from March 7, 2020, through April 30, 2021. RESULTS: Of 625 participating hospitals in 29 states, 393 (63%) reported at least 1 hospital alert during the study period: 246 (63%) reported ED overcrowding, 239 (61%) reported ICU overcrowding, and 48 (12%) reported ventilator shortages. The number of alerts for overcrowding in EDs and ICUs increased as the number of COVID-19 cases surged. CONCLUSIONS: Timely assessment and communication about critical factors such as ED and ICU overcrowding and ventilator shortages during public health emergencies can guide public health response efforts in supporting federal, state, and local public health agencies.
Subject(s)
COVID-19 , COVID-19/epidemiology , Emergency Service, Hospital , Hospitals , Humans , Intensive Care Units , Pandemics , Ventilators, MechanicalABSTRACT
BACKGROUND: Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y). OBJECTIVE: The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS. METHODS: Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels. RESULTS: Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age. CONCLUSIONS: The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.
Subject(s)
Aging/blood , Androstenedione/blood , Hyperandrogenism/blood , Polycystic Ovary Syndrome/blood , Prenatal Exposure Delayed Effects/blood , Testosterone/administration & dosage , Animals , Animals, Newborn , Biomarkers/blood , Disease Models, Animal , Female , Follicle Stimulating Hormone/blood , Hyperandrogenism/chemically induced , Hyperandrogenism/pathology , Luteinizing Hormone/blood , Ovary/drug effects , Ovary/metabolism , Ovary/pathology , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/pathology , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/pathology , Rats , Rats, Sprague-Dawley , Sexual Maturation , Testosterone/bloodABSTRACT
BACKGROUND AND OBJECTIVES: Persons receiving outpatient hemodialysis are at risk for bloodstream and vascular access infections. The Centers for Disease Control and Prevention conducts surveillance for these infections through the National Healthcare Safety Network. We summarize 2014 data submitted to National Healthcare Safety Network Dialysis Event Surveillance. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dialysis facilities report three types of dialysis events (bloodstream infections; intravenous antimicrobial starts; and pus, redness, or increased swelling at the hemodialysis vascular access site). Denominator data consist of the number of hemodialysis outpatients treated at the facility during the first 2 working days of each month. We calculated dialysis event rates stratified by vascular access type (e.g., arteriovenous fistula, arteriovenous graft, or central venous catheter) and standardized infection ratios (comparing individual facility observed with predicted numbers of infections) for bloodstream infections. We described pathogens identified among bloodstream infections. RESULTS: A total of 6005 outpatient hemodialysis facilities reported dialysis event data for 2014 to the National Healthcare Safety Network. These facilities reported 160,971 dialysis events, including 29,516 bloodstream infections, 149,722 intravenous antimicrobial starts, and 38,310 pus, redness, or increased swelling at the hemodialysis vascular access site events; 22,576 (76.5%) bloodstream infections were considered vascular access related. Most bloodstream infections (63.0%) and access-related bloodstream infections (69.8%) occurred in patients with a central venous catheter. The rate of bloodstream infections per 100 patient-months was 0.64 (0.26 for arteriovenous fistula, 0.39 for arteriovenous graft, and 2.16 for central venous catheter). Other dialysis event rates were also highest among patients with a central venous catheter. Facility bloodstream infection standardized infection ratio distribution was positively skewed with a median of 0.84. Staphylococcus aureus was the most commonly isolated bloodstream infection pathogen (30.6%), and 39.5% of S. aureus isolates tested were resistant to methicillin. CONCLUSIONS: The 2014 National Healthcare Safety Network Dialysis Event data represent nearly all United States outpatient dialysis facilities. Rates of infection and other dialysis events were highest among patients with a central venous catheter compared with other vascular access types. Surveillance data can help define the epidemiology of important infections in this patient population.
Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis/adverse effects , Catheter-Related Infections/epidemiology , Catheterization, Central Venous/adverse effects , Central Venous Catheters/adverse effects , Prosthesis-Related Infections/epidemiology , Renal Dialysis/adverse effects , Staphylococcal Infections/epidemiology , Administration, Intravenous , Ambulatory Care , Anti-Infective Agents/administration & dosage , Arteriovenous Shunt, Surgical/instrumentation , Bacteremia/epidemiology , Bacteremia/microbiology , Blood Vessel Prosthesis Implantation/instrumentation , Catheter-Related Infections/diagnosis , Catheter-Related Infections/drug therapy , Catheter-Related Infections/microbiology , Catheterization, Central Venous/instrumentation , Humans , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Population Surveillance , Prognosis , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/microbiology , Quality Indicators, Health Care , Risk Factors , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Time Factors , United States/epidemiologyABSTRACT
While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment. For each of these independent scenarios, we consider one hypothetical cell line that is responsive to metronomic chemotherapy, and another that with high probability cannot be eradicated by a metronomic protocol. Motivated by experimental work on ovarian cancer xenografts, we consider all possible combinations of a one week treatment protocol, repeated for three weeks, and constrained by the total weekly drug dose. Simulations reveal a small number of fractionated-dose protocols that are at least as effective as metronomic therapy in eradicating micrometastases with acquired resistance (weak or strong), while also being at least as effective on those that harbor weakly pre-existing resistant cells. Given the responsiveness of very different theoretical cell lines to these few fractionated-dose protocols, these may represent more effective ways to schedule chemotherapy with the goal of limiting metastatic tumor progression.