Transmission from vaccinated individuals in a large SARS-CoV-2 Delta variant outbreak.

An outbreak of over 1,000 COVID-19 cases in Provincetown, Massachusetts (MA), in July 2021-the first large outbreak mostly in vaccinated individuals in the US-prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined viral genomic and epidemiological data from 467 individuals, including 40% of outbreak-associated cases. The Delta variant accounted for 99% of cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event. Genomic and epidemiological data supported multiple transmissions of Delta from and between fully vaccinated individuals. However, despite its magnitude, the outbreak had limited onward impact in MA and the US overall, likely due to high vaccination rates and a robust public health response.

The power of parent scientists.

Parent scientists lead a journey to bring surveillance severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to public schools across the state of Massachusetts and beyond.

COVID-19-neutralizing antibodies predict disease severity and survival.

Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels. Although anti-RBD immunoglobulin G (IgG) levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from reinfection by either strain. However, SARS-CoV-2 sera generally lacked cross-neutralization to a highly homologous pre-emergent bat coronavirus, WIV1-CoV, which has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.

Engineering a Biological Revolution.

The new field of synthetic biology promises to change health care, computer technology, the production of biofuels, and more. Students participating in the International Genetically Engineered Machine (iGEM) competition are on the front lines of this revolution.

Lifting Universal Masking in Schools - Covid-19 Incidence among Students and Staff.

BACKGROUND: In February 2022, Massachusetts rescinded a statewide universal masking policy in public schools, and many Massachusetts school districts lifted masking requirements during the subsequent weeks. In the greater Boston area, only two school districts - the Boston and neighboring Chelsea districts - sustained masking requirements through June 2022. The staggered lifting of masking requirements provided an opportunity to examine the effect of universal masking policies on the incidence of coronavirus disease 2019 (Covid-19) in schools. METHODS: We used a difference-in-differences analysis for staggered policy implementation to compare the incidence of Covid-19 among students and staff in school districts in the greater Boston area that lifted masking requirements with the incidence in districts that sustained masking requirements during the 2021-2022 school year. Characteristics of the school districts were also compared. RESULTS: Before the statewide masking policy was rescinded, trends in the incidence of Covid-19 were similar across school districts. During the 15 weeks after the statewide masking policy was rescinded, the lifting of masking requirements was associated with an additional 44.9 cases per 1000 students and staff (95% confidence interval, 32.6 to 57.1), which corresponded to an estimated 11,901 cases and to 29.4% of the cases in all districts during that time. Districts that chose to sustain masking requirements longer tended to have school buildings that were older and in worse condition and to have more students per classroom than districts that chose to lift masking requirements earlier. In addition, these districts had higher percentages of low-income students, students with disabilities, and students who were English-language learners, as well as higher percentages of Black and Latinx students and staff. Our results support universal masking as an important strategy for reducing Covid-19 incidence in schools and loss of in-person school days. As such, we believe that universal masking may be especially useful for mitigating effects of structural racism in schools, including potential deepening of educational inequities. CONCLUSIONS: Among school districts in the greater Boston area, the lifting of masking requirements was associated with an additional 44.9 Covid-19 cases per 1000 students and staff during the 15 weeks after the statewide masking policy was rescinded.

A neural network solves, explains, and generates university math problems by program synthesis and few-shot learning at human level.

We demonstrate that a neural network pretrained on text and fine-tuned on code solves mathematics course problems, explains solutions, and generates questions at a human level. We automatically synthesize programs using few-shot learning and OpenAI's Codex transformer and execute them to solve course problems at 81% automatic accuracy. We curate a dataset of questions from Massachusetts Institute of Technology (MIT)'s largest mathematics courses (Single Variable and Multivariable Calculus, Differential Equations, Introduction to Probability and Statistics, Linear Algebra, and Mathematics for Computer Science) and Columbia University's Computational Linear Algebra. We solve questions from a MATH dataset (on Prealgebra, Algebra, Counting and Probability, Intermediate Algebra, Number Theory, and Precalculus), the latest benchmark of advanced mathematics problems designed to assess mathematical reasoning. We randomly sample questions and generate solutions with multiple modalities, including numbers, equations, and plots. The latest GPT-3 language model pretrained on text automatically solves only 18.8% of these university questions using zero-shot learning and 30.8% using few-shot learning and the most recent chain of thought prompting. In contrast, program synthesis with few-shot learning using Codex fine-tuned on code generates programs that automatically solve 81% of these questions. Our approach improves the previous state-of-the-art automatic solution accuracy on the benchmark topics from 8.8 to 81.1%. We perform a survey to evaluate the quality and difficulty of generated questions. This work automatically solves university-level mathematics course questions at a human level and explains and generates university-level mathematics course questions at scale, a milestone for higher education.

The Safety of Outpatient Health Care : Review of Electronic Health Records.

BACKGROUND: Despite considerable emphasis on delivering safe care, substantial patient harm occurs. Although most care occurs in the outpatient setting, knowledge of outpatient adverse events (AEs) remains limited. OBJECTIVE: To measure AEs in the outpatient setting. DESIGN: Retrospective review of the electronic health record (EHR). SETTING: 11 outpatient sites in Massachusetts in 2018. PATIENTS: 3103 patients who received outpatient care. MEASUREMENTS: Using a trigger method, nurse reviewers identified possible AEs and physicians adjudicated them, ranked severity, and assessed preventability. Generalized estimating equations were used to assess the association of having at least 1 AE with age, sex, race, and primary insurance. Variation in AE rates was analyzed across sites. RESULTS: The 3103 patients (mean age, 52 years) were more often female (59.8%), White (75.1%), English speakers (90.8%), and privately insured (70.4%) and had a mean of 4 outpatient encounters in 2018. Overall, 7.0% (95% CI, 4.6% to 9.3%) of patients had at least 1 AE (8.6 events per 100 patients annually). Adverse drug events were the most common AE (63.8%), followed by health care-associated infections (14.8%) and surgical or procedural events (14.2%). Severity was serious in 17.4% of AEs, life-threatening in 2.1%, and never fatal. Overall, 23.2% of AEs were preventable. Having at least 1 AE was less often associated with ages 18 to 44 years than with ages 65 to 84 years (standardized risk difference, -0.05 [CI, -0.09 to -0.02]) and more often associated with Black race than with Asian race (standardized risk difference, 0.09 [CI, 0.01 to 0.17]). Across study sites, 1.8% to 23.6% of patients had at least 1 AE and clinical category of AEs varied substantially. LIMITATION: Retrospective EHR review may miss AEs. CONCLUSION: Outpatient harm was relatively common and often serious. Adverse drug events were most frequent. Rates were higher among older adults. Interventions to curtail outpatient harm are urgently needed. PRIMARY FUNDING SOURCE: Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.

Medicaid Inmate Exclusion Policy and Infectious Diseases Care for Justice-Involved Populations.

The Medicaid Inmate Exclusion Policy (MIEP) prohibits using federal funds for ambulatory care services and medications (including for infectious diseases) for incarcerated persons. More than one quarter of states, including California and Massachusetts, have asked the federal government for authority to waive the MIEP. To improve health outcomes and continuation of care, those states seek to cover transitional care services provided to persons in the period before release from incarceration. The Massachusetts Sheriffs' Association, Massachusetts Department of Correction, Executive Office of Health and Human Services, and University of Massachusetts Chan Medical School have collaborated to improve infectious disease healthcare service provision before and after release from incarceration. They seek to provide stakeholders working at the intersection of criminal justice and healthcare with tools to advance Medicaid policy and improve treatment and prevention of infectious diseases for persons in jails and prisons by removing MIEP barriers through Section 1115 waivers.

Electronic Health Record Data for Lyme Disease Surveillance, Massachusetts, USA, 2017-2018.

Lyme disease surveillance based on provider and laboratory reports underestimates incidence. We developed an algorithm for automating surveillance using electronic health record data. We identified potential Lyme disease markers in electronic health record data (laboratory tests, diagnosis codes, prescriptions) from January 2017-December 2018 in 2 large practice groups in Massachusetts, USA. We calculated their sensitivities and positive predictive values (PPV), alone and in combination, relative to medical record review. Sensitivities ranged from 57% (95% CI 47%-69%) for immunoassays to 87% (95% CI 70%-100%) for diagnosis codes. PPVs ranged from 53% (95% CI 43%-61%) for diagnosis codes to 58% (95% CI 50%-66%) for immunoassays. The combination of a diagnosis code and antibiotics within 14 days or a positive Western blot had a sensitivity of 100% (95% CI 86%-100%) and PPV of 82% (95% CI 75%-89%). This algorithm could make Lyme disease surveillance more efficient and consistent.

Electronic Health Record-Based Algorithm for Monitoring Respiratory Virus-Like Illness.

Viral respiratory illness surveillance has traditionally focused on single pathogens (e.g., influenza) and required fever to identify influenza-like illness (ILI). We developed an automated system applying both laboratory test and syndrome criteria to electronic health records from 3 practice groups in Massachusetts, USA, to monitor trends in respiratory viral-like illness (RAVIOLI) across multiple pathogens. We identified RAVIOLI syndrome using diagnosis codes associated with respiratory viral testing or positive respiratory viral assays or fever. After retrospectively applying RAVIOLI criteria to electronic health records, we observed annual winter peaks during 2015-2019, predominantly caused by influenza, followed by cyclic peaks corresponding to SARS-CoV-2 surges during 2020-2024, spikes in RSV in mid-2021 and late 2022, and recrudescent influenza in late 2022 and 2023. RAVIOLI rates were higher and fluctuations more pronounced compared with traditional ILI surveillance. RAVIOLI broadens the scope, granularity, sensitivity, and specificity of respiratory viral illness surveillance compared with traditional ILI surveillance.

Multiple prenatal exposures and acute-care clinical encounters for asthma among children born to mothers living near a Superfund site.

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P <.001). HRs were higher for girls (HR = 4.17; 95% CI, 3.60-4.82) than for boys (HR = 1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology.

Missing data and missed infections: investigating racial and ethnic disparities in SARS-CoV-2 testing and infection rates in Holyoke, Massachusetts.

Routinely collected testing data have been a vital resource for public health response during the COVID-19 pandemic and have revealed the extent to which Black and Hispanic persons have borne a disproportionate burden of SARS-CoV-2 infections and hospitalizations in the United States. However, missing race and ethnicity data and missed infections due to testing disparities limit the interpretation of testing data and obscure the true toll of the pandemic. We investigated potential bias arising from these 2 types of missing data through a case study carried out in Holyoke, Massachusetts, during the prevaccination phase of the pandemic. First, we estimated SARS-CoV-2 testing and case rates by race and ethnicity, imputing missing data using a joint modeling approach. We then investigated disparities in SARS-CoV-2 reported case rates and missed infections by comparing case rate estimates with estimates derived from a COVID-19 seroprevalence survey. Compared with the non-Hispanic White population, we found that the Hispanic population had similar testing rates (476 tested per 1000 vs 480 per 1000) but twice the case rate (8.1% vs 3.7%). We found evidence of inequitable testing, with a higher rate of missed infections in the Hispanic population than in the non-Hispanic White population (79 infections missed per 1000 vs 60 missed per 1000).

The Impact of Common Variations in Sequential Organ Failure Assessment Score Calculation on Sepsis Measurement Using Sepsis-3 Criteria: A Retrospective Analysis Using Electronic Health Record Data.

OBJECTIVES: To assess the impact of different methods of calculating Sequential Organ Failure Assessment (SOFA) scores using electronic health record data on the incidence, outcomes, agreement, and predictive validity of Sepsis-3 criteria. DESIGN: Retrospective observational study. SETTING: Five Massachusetts hospitals. PATIENTS: Hospitalized adults, 2015 to 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined sepsis as a suspected infection (culture obtained and antibiotic administered) with a concurrent increase in SOFA score by greater than or equal to 2 points (Sepsis-3 criteria). Our reference SOFA implementation strategy imputed normal values for missing data, used Pa o2 /F io2 ratios for respiratory scores, and assumed normal baseline SOFA scores for community-onset sepsis. We then implemented SOFA scores using different missing data imputation strategies (averaging worst values from preceding and following days vs. carrying forward nonmissing values), imputing respiratory scores using Sp o2 /F io2 ratios, and incorporating comorbidities and prehospital laboratory data into baseline SOFA scores. Among 1,064,459 hospitalizations, 297,512 (27.9%) had suspected infection and 141,052 (13.3%) had sepsis with an in-hospital mortality rate of 10.3% using the reference SOFA method. The percentage of patients missing SOFA components for at least 1 day in the infection window was highest for Pa o2 /F io2 ratios (98.6%), followed by Sp o2 /F io2 ratios (73.5%), bilirubin (68.5%), and Glasgow Coma Scale scores (57.2%). Different missing data imputation strategies yielded near-perfect agreement in identifying sepsis (kappa 0.99). However, using Sp o2 /F io2 imputations yielded higher sepsis incidence (18.3%), lower mortality (8.1%), and slightly lower predictive validity for mortality (area under the receiver operating curves [AUROC] 0.76 vs. 0.78). For community-onset sepsis, incorporating comorbidities and historical laboratory data into baseline SOFA score estimates yielded lower sepsis incidence (6.9% vs. 11.6%), higher mortality (13.4% vs. 9.6%), and higher predictive validity (AUROC 0.79 vs. 0.75) relative to the reference SOFA implementation. CONCLUSIONS: Common variations in calculating respiratory and baseline SOFA scores, but not in handling missing data, lead to substantial differences in observed incidence, mortality, agreement, and predictive validity of Sepsis-3 criteria.

Patterns of Social Needs Predict Quality-of-Life and Healthcare Utilization Outcomes in Patients from a Large Hospital System.

BACKGROUND: Unmet social needs (SNs) often coexist in distinct patterns within specific population subgroups, yet these patterns are understudied. OBJECTIVE: To identify patterns of social needs (PSNs) and characterize their associations with health-related quality-of-life (HRQoL) and healthcare utilization (HCU). DESIGN: Observational study using data on SNs screening, HRQoL (i.e., low mental and physical health), and 90-day HCU (i.e., emergency visits and hospital admission). Among patients with any SNs, latent class analysis was conducted to identify unique PSNs. For all patients and by race and age subgroups, compared with no SNs, we calculated the risks of poor HRQoL and time to first HCU following SNs screening for each PSN. PATIENTS: Adult patients undergoing SNs screening at the Mass General Brigham healthcare system in Massachusetts, United States, between March 2018 and January 2023. MAIN MEASURES: SNs included: education, employment, family care, food, housing, medication, transportation, and ability to pay for household utilities. HRQoL was assessed using the Patient-Reported Outcomes Measurement Information System Global-10. KEY RESULTS: Six unique PSNs were identified: "high number of social needs," "food and utility access," "employment needs," "interested in education," "housing instability," and "transportation barriers." In 14,230 patients with HRQoL data, PSNs increased the risks of poor mental health, with risk ratios ranging from 1.07(95%CI:1.01-1.13) to 1.80(95%CI:1.74-1.86). Analysis of poor physical health yielded similar findings, except that the "interested in education" showed a mild protective effect (0.97[95%CI:0.94-1.00]). In 105,110 patients, PSNs increased the risk of 90-day HCU, with hazard ratios ranging from 1.09(95%CI:0.99-1.21) to 1.70(95%CI:1.52-1.90). Findings were generally consistent in subgroup analyses by race and age. CONCLUSIONS: Certain SNs coexist in distinct patterns and result in poorer HRQoL and more HCU. Understanding PSNs allows policymakers, public health practitioners, and social workers to identify at-risk patients and implement integrated, system-wide, and community-based interventions.

Bundling Colorectal Cancer Screening Outreach with Screening for Social Risk in Federally Qualified Health Centers: A Stepped-Wedge Implementation-Effectiveness Study.

BACKGROUND: Bundling is combining individual interventions to meet quality metrics. Bundling offers of cancer screening with screening for social determinants of health (SDOH) may enable health centers to assist patients with social risks and yield efficiencies. OBJECTIVE: To measure effects of bundling fecal immunochemical testing (FIT) and SDOH screening in federally qualified health centers (FQHCs). DESIGN: Clustered stepped-wedge trial. PARTICIPANTS: Four Massachusetts FQHCs randomized to implement bundled FIT-SDOH over 8-week "steps." INTERVENTION: Outreach to 50-75-year-olds overdue for CRC screening to offer FIT with SDOH screening. The implementation strategy used facilitation and training for data monitoring and reporting. MAIN MEASURES: Implementation process descriptions, data from facilitation meetings, and CRC and SDOH screening rates. Rates were compared between implementation and control FQHCs in each "step" by fitting generalized linear mixed-effects models with random intercepts for FQHCs, patients, and "step" by FQHC. KEY RESULTS: FQHCs tailored implementation processes to their infrastructure, workflows, and staffing and prioritized different groups for outreach. Two FQHCs used population health outreach, and two integrated FIT-SDOH within established programs, such as pre-visit planning. Of 34,588 patients overdue for CRC screening, 54% were female; 20% Black, 11% Latino, 10% Asian, and 47% white; 32% had Medicaid, 16% Medicare, 32% private insurance, and 11% uninsured. Odds of CRC screening completion in implementation "steps" compared to controls were higher overall and among groups prioritized for outreach (overall: adjusted odds ratio (aOR) 2.41, p = 0.005; prioritized: aOR 2.88, p = 0.002). Odds of SDOH screening did not differ across "steps." CONCLUSIONS: As healthcare systems are required to conduct more screenings, it is notable that outreach for a long-standing cancer screening requirement increased screening, even when bundled with a newer screening requirement. This outreach was feasible in a real-world safety-net clinical population and may conserve resources, especially compared to more complex or intensive outreach strategies. CLINICAL TRIALS REGISTRATION: NCT04585919.

Factors Associated With Delays in Presentation and Treatment of Gonorrhea, Massachusetts 2015-2019.

BACKGROUND: Rates of gonorrhea are increasing across the United States. Understanding and addressing contributing factors associated with longer time to diagnosis and treatment may shorten the duration of infectiousness, which in turn may limit transmission. METHODS: We used Massachusetts data from the US Centers for Disease Control and Prevention Sexually Transmitted Disease Surveillance Network collected between July 2015 and September 2019, along with routinely reported surveillance data, to assess time from gonorrhea symptom onset to presentation to care, and time from presentation to care to receipt of treatment. Factors associated with longer time to presentation (TTP) and time to treatment (TTT) were assessed using Cox proportional hazard models with a constant time variable. RESULTS: Among symptomatic patients (n = 672), 31% did not receive medical care within 7 days of symptom onset. Longer TTP was associated with younger age, female gender, reporting cost as a barrier to care, and provider report of proctitis. Among patients with symptoms and/or known contact to gonorrhea (n = 827), 42% did not receive presumptive treatment. Longer TTT was associated with female gender, non-Hispanic other race/ethnicity, and clinics with less gonorrhea treatment experience. Among asymptomatic patients without known exposure to STI (n = 235), 26% did not receive treatment within 7 days. Longer TTT was associated with sexually transmitted disease clinic/family planning/reproductive health clinics and a test turnaround time of ≥3 days. CONCLUSIONS: Delays in presentation to care and receipt of treatment for gonorrhea are common. Factors associated with longer TTP and TTT highlight multiple opportunities for reducing the infectious period of patients with gonorrhea.

Direct-to-Consumer Advertising Survey of Psychiatrists in Massachusetts and Michigan.

PURPOSES/BACKGROUND: The goals of this preliminary study were to survey psychiatrists and to examine the impact of advertisements on their prescription of psychotropic medications. The study specifically looked at psychiatrists in Massachusetts and Michigan, as the authors were able to readily contact the members of their respective state psychiatric societies. METHODS/PROCEDURES: We used the survey software, Quatrics, to create an online survey that was sent via email link to the members of the Massachusetts Psychiatric Society (1400 estimated members), and the Michigan Psychiatric Society (700 estimated members). Details were obtained about how challenging it was for the psychiatrist to convince the patient that a medication was not indicated. Information regarding how the psychiatrist first heard about new medications and where they go to learn more about these medications was included in the survey. FINDINGS/RESULTS: We received 162 partial or full responses to our survey, representing a response rate of 8%. Those who were less than 10 years out of training were less likely to find it "easy" to change the minds of these patients, when compared with those more than 10 years out of training (Fisher exact test, P = 0.0396). The most frequent medication named as a response to "which medications do patients request" was Rexulti (brexpiprazole), followed by Vraylar (cariprazine), Caplyta (lumateperone), and aripiprazole. IMPLICATIONS/CONCLUSIONS: This survey points to the prevalence of psychiatrists getting requests for these advertised medications and illustrates that those with fewer years out of training may have a more difficult time redirecting patients from medications that are not indicated for their illness.

How do we use the National Healthcare Safety Network for Hemovigilance in Massachusetts?

BACKGROUND: Use of the National Healthcare Safety Network (NHSN) has been essential to the success of the Massachusetts Hemovigilance Program and has allowed for the timely identification of signals and trends over a defined population that correlate with national and international hemovigilance (HV) data. Here, we outline how the NHSN system is used for monitoring HV data in Massachusetts and encourage adoption of NHSN for nationwide HV surveillance. STUDY DESIGN AND METHODS: A collaboration that grew over time between local HV stakeholders and the Massachusetts Department of Public Health (MDPH) resulted in the change from a paper-based method of reporting adverse reactions and monthly transfusion activity for compliance with state requirements to replacement with statewide adoption of reporting via NHSN. RESULTS: Over 1.5 million blood products were transfused in Massachusetts between 2017 and 2021, with 3000 adverse reactions among 10 defined types reported. Using NHSN, MDPH has been able to produce numerous reports, publications, and presentations that have made previously non-obtainable HV and blood utilization data available. DISCUSSION: Although limitations to these self-reported data exist, such as lack of external validation, successful statewide implementation of NHSN for hospital blood bank reporting is possible and has benefits beyond those for regulatory oversight. It results in standardized, actionable data at both the hospital and state level, enabling inter-facility comparisons, benchmarking, and opportunities for practice improvement.