Adaptive COVID-19 Mitigation Strategies: Tradeoffs between Trigger Thresholds, Response Timing, and Effectiveness.

Background. To support proactive decision making during the COVID-19 pandemic, mathematical models have been leveraged to identify surveillance indicator thresholds at which strengthening nonpharmaceutical interventions (NPIs) is necessary to protect health care capacity. Understanding tradeoffs between different adaptive COVID-19 response components is important when designing strategies that balance public preference and public health goals. Methods. We considered 3 components of an adaptive COVID-19 response: 1) the threshold at which to implement the NPI, 2) the time needed to implement the NPI, and 3) the effectiveness of the NPI. Using a compartmental model of SARS-CoV-2 transmission calibrated to Minnesota state data, we evaluated different adaptive policies in terms of the peak number of hospitalizations and the time spent with the NPI in force. Scenarios were compared with a reference strategy, in which an NPI with an 80% contact reduction was triggered when new weekly hospitalizations surpassed 8 per 100,000 population, with a 7-day implementation period. Assumptions were varied in sensitivity analysis. Results. All adaptive response scenarios substantially reduced peak hospitalizations relative to no response. Among adaptive response scenarios, slower NPI implementation resulted in somewhat higher peak hospitalization and a longer time spent under the NPIs than the reference scenario. A stronger NPI response resulted in slightly less time with the NPIs in place and smaller hospitalization peak. A higher trigger threshold resulted in greater peak hospitalizations with little reduction in the length of time under the NPIs. Conclusions. An adaptive NPI response can substantially reduce infection circulation and prevent health care capacity from being exceeded. However, population preferences as well as the feasibility and timeliness of compliance with reenacting NPIs should inform response design. Highlights: This study uses a mathematical model to compare different adaptive nonpharmaceutical intervention (NPI) strategies for COVID-19 management across 3 dimensions: threshold when the NPI should be implemented, time it takes to implement the NPI, and the effectiveness of the NPI.All adaptive NPI response scenarios considered substantially reduced peak hospitalizations compared with no response.Slower NPI implementation results in a somewhat higher peak hospitalization and longer time spent with the NPI in place but may make an adaptive strategy more feasible by allowing the population sufficient time to prepare for changing restrictions.A stronger, more effective NPI response results in a modest reduction in the time spent under the NPIs and slightly lower peak hospitalizations.A higher threshold for triggering the NPI delays the time at which the NPI starts but results in a higher peak hospitalization and does not substantially reduce the time the NPI remains in force.

Discussing Cervical Cancer Screening Options: Outcomes to Guide Conversations Between Patients and Providers.

Purpose. In 2018, the US Preventive Services Task Force (USPSTF) endorsed three strategies for cervical cancer screening in women ages 30 to 65: cytology every 3 years, testing for high-risk types of human papillomavirus (hrHPV) every 5 years, and cytology plus hrHPV testing (co-testing) every 5 years. It further recommended that women discuss with health care providers which testing strategy is best for them. To inform such discussions, we used decision analysis to estimate outcomes of screening strategies recommended for women at age 30. Methods. We constructed a Markov decision model using estimates of the natural history of HPV and cervical neoplasia. We evaluated the three USPSTF-endorsed strategies, hrHPV testing every 3 years and no screening. Outcomes included colposcopies with biopsy, false-positive testing (a colposcopy in which no cervical intraepithelial neoplasia grade 2 or worse was found), treatments, cancers, and cancer mortality expressed per 10,000 women over a shorter-than-lifetime horizon (15-year). Results. All strategies resulted in substantially lower cancer and cancer death rates compared with no screening. Strategies with the lowest likelihood of cancer and cancer death generally had higher likelihood of colposcopy and false-positive testing. Conclusions. The screening strategies we evaluated involved tradeoffs in terms of benefits and harms. Because individual women may place different weights on these projected outcomes, the optimal choice for each woman may best be discerned through shared decision making.

Estimated Quality of Life and Economic Outcomes Associated With 12 Cervical Cancer Screening Strategies: A Cost-effectiveness Analysis.

Importance: Many cervical cancer screening strategies are now recommended in the United States, but the benefits, harms, and costs of each option are unclear. Objective: To estimate the cost-effectiveness of 12 cervical cancer screening strategies. Design, Setting, and Participants: The cross-sectional portion of this study enrolled a convenience sample of 451 English-speaking or Spanish-speaking women aged 21 to 65 years from September 22, 2014, to June 16, 2016, identified at women's health clinics in San Francisco. In this group, utilities (preferences) were measured for 23 cervical cancer screening-associated health states and were applied to a decision model of type-specific high-risk human papillomavirus (hrHPV)-induced cervical carcinogenesis. Test accuracy estimates were abstracted from systematic reviews. The evaluated strategies were cytologic testing every 3 years for women aged 21 to 65 years with either repeat cytologic testing in 1 year or immediate hrHPV triage for atypical squamous cells of undetermined significance (ASC-US), cytologic testing every 3 years for women age 21 to 29 years followed by cytologic testing plus hrHPV testing (cotesting), or primary hrHPV testing alone for women aged 30 to 65 years. Screening frequency, abnormal test result management, and the age to switch from cytologic testing to hrHPV testing (25 or 30 years) were varied. Analyses were conducted from both the societal and health care sector perspectives. Main Outcomes and Measures: Utilities for 23 cervical cancer screening-associated health states (cross-sectional study) and quality-adjusted life-years (QALYs) and total costs for each strategy. Results: Utilities were measured in a sociodemographically diverse group of 451 women (mean [SD] age, 38.2 [10.7] years; 258 nonwhite [57.2%]). Cytologic testing every 3 years with repeat cytologic testing for ASC-US yielded the most lifetime QALYs and conferred more QALYs at higher costs ($2166 per QALY) than the lowest-cost strategy (cytologic testing every 3 years with hrHPV triage of ASC-US). All cytologic testing plus hrHPV testing (cotesting) and primary hrHPV testing strategies provided fewer QALYs at higher costs. Adding indirect costs did not change the conclusions. In sensitivity analyses, hrHPV testing every 5 years with genotyping triage beginning at age 30 years was the lowest-cost strategy when hrHPV test sensitivity was markedly higher than cytologic test sensitivity or when hrHPV test cost was equated to the lowest reported cytologic test cost ($14). Conclusions and Relevance: Cytologic testing every 3 years for women aged 21 to 29 years with either continued cytologic testing every 3 years or switching to a low-cost hrHPV test every 5 years confers a reasonable balance of benefits, harms, and costs. Comparative modeling is needed to confirm the association of these novel utilities with cost-effectiveness.

Cost-effectiveness of pre-operative Staphylococcus aureus screening and decolonization.

OBJECTIVE: We developed a decision analytic model to evaluate the impact of a preoperative Staphylococcus aureus decolonization bundle on surgical site infections (SSIs), health-care-associated costs (HCACs), and deaths due to SSI. METHODS: Our model population comprised US adults undergoing elective surgery. We evaluated 3 self-administered preoperative strategies: (1) the standard of care (SOC) consisting of 2 disinfectant soap showers; (2) the "test-and-treat" strategy consisting of the decolonization bundle including chlorhexidine gluconate (CHG) soap, CHG mouth rinse, and mupirocin nasal ointment for 5 days) if S. aureus was found at any of 4 screened sites (nasal, throat, axillary, perianal area), otherwise the SOC; and (3) the "treat-all" strategy consisting of the decolonization bundle for all patients, without S. aureus screening. Model parameters were derived primarily from a randomized controlled trial that measured the efficacy of the decolonization bundle for eradicating S. aureus. RESULTS: Under base-case assumptions, the treat-all strategy yielded the fewest SSIs and the lowest HCACs, followed by the test-and-treat strategy. In contrast, the SOC yielded the most SSIs and the highest HCACs. Consequently, relative to the SOC, the average savings per operation was $217 for the treat-all strategy and $123 for the test-and-treat strategy, and the average savings per per SSI prevented was $21,929 for the treat-all strategy and $15,166 for the test-and-treat strategy. All strategies were sensitive to the probability of acquiring an SSI and the increased risk if SSI if the patient was colonized with SA. CONCLUSION: We predict that the treat-all strategy would be the most effective and cost-saving strategy for preventing SSIs. However, because this strategy might select more extensively for mupirocin-resistant S. aureus and cause more medication adverse effects than the test-and-treat approach or the SOC, additional studies are needed to define its comparative benefits and harms.

Pertussis and the Minnesota State Fair: Demonstrating a Novel Setting for Efficiently Conducting Seroepidemiologic Studies.

Seroepidemiologic studies, which measure serum antibody levels produced in response to infection and/or vaccination, can be valuable tools for gaining insight into population level dynamics of infectious diseases. However, because seroepidemiologic studies are expensive and logistically challenging, they are not routinely conducted for surveillance purposes. We have identified a novel venue, state fairgrounds, in which annual sera samples from a population may be rapidly collected with minimal recruitment expenses. We conducted a pilot pertussis seroepidemiologic study over the course of 3 days at the 2016 Minnesota State Fair to determine if this setting, which hosts nearly 2 million visitors over 12 days each year, is viable for facilitating larger seroepidemiologic studies. A total of 104 adults and children were enrolled to provide a finger stick blood sample for serologic testing and to take a written survey regarding recent cough illness and pertussis vaccination. The survey was used to distinguish between antibodies induced by vaccination and pertussis infection. Elevated antibodies suggestive of recent infection were found among two adults. The prevalence of undetectable antibodies, suggestive of susceptibility, was 72.3% (95% CI 59.6, 85.1%) among 7-17 year olds, 53.8% (95% CI 26.7, 80.9%) among 1-6 year olds, and 23.3% (95% CI 8.2, 38.5%) among adults. Our ability to rapidly enroll participants and collect satisfactory specimens suggests that seroepidemiologic studies with 1000-2000 participants could efficiently be completed over the 12-day course of the Minnesota State Fair. This setting raises the possibility of efficiently conducting annual population-based seroepidemiologic studies to supplement traditional public health surveillance in estimating disease prevalence, monitoring vaccine impact, and identifying at-risk groups.

Understanding Trends in Pertussis Incidence: An Agent-Based Model Approach.

OBJECTIVES: We examined the impact of undetected infections, adult immunity, and waning vaccine-acquired immunity on recent age-related trends in pertussis incidence. METHODS: We developed an agent-based model of pertussis transmission in Dakota County, Minnesota using case data from the Minnesota Department of Health. For outbreaks in 2004, 2008, and 2012, we fit our model to incidence in 3 children's age groups relative to adult incidence. We estimated parameters through model calibration. RESULTS: The duration of vaccine-acquired immunity after completion of the 5-dose vaccination series decreased from 6.6 years in the 2004 model to approximately 3.0 years in the 2008 and 2012 models. Tdap waned after 2.1 years in the 2012 model. A greater percentage of adults were immune in the 2008 model than in the 2004 and 2012 models. On average, only 1 in 10 adult infections was detected, whereas 8 in 10 child infections were detected. CONCLUSIONS: The observed trends in relative pertussis incidence in Dakota County can be attributed in part to fluctuations in adult immunity and waning vaccine-acquired immunity. No single factor accounts for current pertussis trends.