A narrative review of norovirus epidemiology, biology, and challenges to vaccine development.

Norovirus is a leading cause of acute gastroenteritis (AGE) globally. AGE resulting from norovirus causes significant morbidity and mortality in countries of all income levels, particularly among young children and older adults. Prevention of norovirus AGE represents a unique challenge as the virus is genetically diverse with multiple genogroups and genotypes cocirculating globally and causing disease in humans. Variants of the GII.4 genotype are typically the most common genotype, and other genotypes cause varying amounts of disease year-to-year, with GII.2, GII.3, and GII.6 most prevalent in recent years. Noroviruses are primarily transmitted via the fecal-oral route and only a very small number of virions are required for infection, which makes outbreaks of norovirus extremely difficult to control when they occur. Settings like long-term care facilities, daycares, and hospitals are at high risk of outbreaks and can have very high attack rates resulting in substantial costs and disease burden. Severe cases of norovirus AGE are most common in vulnerable patient populations, such as infants, the elderly, and immunocompromised individuals, with available treatments limited to rehydration therapies and supportive care. To date, there are no FDA-approved norovirus vaccines; however, several candidates are currently in development. Given the substantial human and economic burden associated with norovirus AGE, a vaccine to prevent morbidity and mortality and protect vulnerable populations could have a significant impact on global public health.

Treatment Patterns of Bone-targeting Agents Among Solid Tumor Patients With Bone Metastases: An Analysis of Electronic Health Record Data in the United States From 2014 to 2018.

OBJECTIVES: This study evaluated real-world treatment patterns of approved bone-targeting agents (BTAs) with various mechanisms of action-pamidronate, zoledronic acid, and denosumab-for the prevention of skeletal-related events in patients with bone metastases (BM) from solid tumors. METHODS: Adult patients with BM secondary to solid tumors between January 1, 2014, and December 31, 2018, were identified from the Flatiron Health Oncology Services Comprehensive Electronic Records database and categorized by BTA use and therapy type. Time from diagnosis to initiation, persistence (mean time on treatment), and compliance (≥12 administrations/year) with BTA with up to 4 years of follow-up were examined. RESULTS: This study included 27,268 patients with BM (breast cancer, 32.7%; lung cancer, 16.5%; prostate cancer, 17.2%; and other solid tumors, 33.6%); of these, 41.4% initiated denosumab after BM diagnosis; 21.3%, zoledronic acid; 0.6%, pamidronate; and 36.7% had no treatment record. Mean (SD) time to initiation for denosumab or zoledronic acid was 68.6 (157.0) days (denosumab, 70.3 (160.4) days; zoledronic acid, 65.2 [150.2] days). Mean persistence and compliance (first year of treatment) were significantly higher for denosumab than for zoledronic acid (22.0 vs. 14.9 mo [ P <0.0001] and 42.3% vs. 34.8% [ P <0.0001], respectively). Treatment compliance was the highest in patients with breast cancer (denosumab, 48.2%; zoledronic acid, 39.1%). CONCLUSION: Real-world BTA treatment patterns in the United States suggest that over one-third of patients with BM secondary to solid tumors remain untreated and less than 50% of the patients received ≥12 administrations/year of BTA therapy.

Systematic literature review of the epidemiology of glycogen storage disease type 1a.

Glycogen storage disease (GSD) type 1a is an inherited autosomal recessive metabolic disease caused by a deficiency in glucose-6-phosphatase activity. The objectives of this research were to systematically review the published literature on the epidemiology of GSD 1a and to assess the performance of reported epidemiology measures in a simulation model. In this systematic literature review 2,539 record titles and abstracts were screened. Of these, only 11 studies contained relevant data on GSD 1a disease epidemiology. Reported disease frequency ranged from 0.085/100,000 to 10.3/100,000 newborns when considering all the GSD literature. When this was narrowed to GSD 1 and GSD 1a, the range was tightened to 0.25-3.02/100,000 and 0.085-4.9/100,000 newborns, respectively. Most of the identified studies counted the number of diagnoses in a defined period and related to the number of births in the same (Dx method) or different time period (DoB method). The simulation model results indicate that in most of the situations, the Dx method provides a closer estimate to the true disease incidence than the DoB method. Despite the scarcity of epidemiology data, the results of this systematic review strongly support that GSD 1a and its parent disease groups (GSD and GSD 1) are rare diseases.

Development and Validation of Algorithms to Identify COVID-19 Patients Using a US Electronic Health Records Database: A Retrospective Cohort Study.

Introduction: In order to identify and evaluate candidate algorithms to detect COVID-19 cases in an electronic health record (EHR) database, this study examined and compared the utilization of acute respiratory disease codes from February to August 2020 versus the corresponding time period in the 3 years preceding. Methods: De-identified EHR data were used to identify codes of interest for candidate algorithms to identify COVID-19 patients. The number and proportion of patients who received a SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) within ±10 days of the occurrence of the diagnosis code and patients who tested positive among those with a test result were calculated, resulting in 11 candidate algorithms. Sensitivity, specificity, and likelihood ratios assessed the candidate algorithms by clinical setting and time period. We adjusted for potential verification bias by weighting by the reciprocal of the estimated probability of verification. Results: From January to March 2020, the most commonly used diagnosis codes related to COVID-19 diagnosis were R06 (dyspnea) and R05 (cough). On or after April 1, 2020, the code with highest sensitivity for COVID-19, U07.1, had near perfect adjusted sensitivity (1.00 [95% CI 1.00, 1.00]) but low adjusted specificity (0.32 [95% CI 0.31, 0.33]) in hospitalized patients. Discussion: Algorithms based on the U07.1 code had high sensitivity among hospitalized patients, but low specificity, especially after April 2020. None of the combinations of ICD-10-CM codes assessed performed with a satisfactory combination of high sensitivity and high specificity when using the SARS-CoV-2 RT-PCR as the reference standard.

Trends in characteristics and outcomes among US adults hospitalised with COVID-19 throughout 2020: an observational cohort study.

OBJECTIVES: To examine the temporal patterns of patient characteristics, treatments used and outcomes associated with COVID-19 in patients who were hospitalised for the disease between January and 15 November 2020. DESIGN: Observational cohort study. SETTING: COVID-19 subset of the Optum deidentified electronic health records, including more than 1.8 million patients from across the USA. PARTICIPANTS: There were 51 510 hospitalised patients who met the COVID-19 definition, with 37 617 in the laboratory positive cohort and 13 893 in the clinical cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident acute clinical outcomes, including in-hospital all-cause mortality. RESULTS: Respectively, 48% and 49% of the laboratory positive and clinical cohorts were women. The 50- 65 age group was the median age group for both cohorts. The use of antivirals and dexamethasone increased over time, fivefold and twofold, respectively, while the use of hydroxychloroquine declined by 98%. Among adult patients in the laboratory positive cohort, absolute age/sex standardised incidence proportion for in-hospital death changed by -0.036 per month (95% CI -0.042 to -0.031) from March to June 2020, but remained fairly flat from June to November, 2020 (0.001 (95% CI -0.001 to 0.003), 17.5% (660 deaths /3986 persons) in March and 10.2% (580/5137) in October); in the clinical cohort, the corresponding changes were -0.024 (95% CI -0.032 to -0.015) and 0.011 (95% CI 0.007 0.014), respectively (14.8% (175/1252) in March, 15.3% (189/1203) in October). Declines in the cumulative incidence of most acute clinical outcomes were observed in the laboratory positive cohort, but not for the clinical cohort. CONCLUSION: The incidence of adverse clinical outcomes remains high among COVID-19 patients with clinical diagnosis only. Patients with COVID-19 entering the hospital are at elevated risk of adverse outcomes.

Assessment of Bone Health Education in US Multiple Myeloma and Solid Tumor Patients at Risk for Skeletal-Related Events.

PURPOSE: Cancer patients with bone metastasis (BM) from solid tumors or multiple myeloma (MM) have an increased risk of painful skeletal-related events (SREs), which can decrease quality of life and increase mortality. Bone targeting agents (BTAs) can help delay or prevent SREs; however, a significant portion of eligible patients are not receiving BTA therapy. This study was conducted to understand patient awareness of cancer-related bone health and to identify opportunities to improve bone health education in cancer patients at risk of SREs. METHODS: The online BonE heAlth eduCatiOn Needs assessment (BEACON) survey included questions about patient demographics, cancer diagnosis and treatments (including BTA usage), and extent and satisfaction with bone health education received. Direct-to-patient outreach was used to recruit patients. Eligible patients were US adults with a diagnosis of self-reported MM or BM from a solid tumor (breast, lung, or prostate cancer) within the past three years. RESULTS: Of 125 patients, 71% were diagnosed with solid tumors with BM and 29% with MM. At least one prior SRE was experienced by 57% of patients (38% radiation to bone, 32% bone fracture, 22% spinal cord compression, and 19% surgery to bone), and 74% were currently receiving BTA therapy. Awareness of cancer bone health, protection strategies, and screening tests was low to moderate; patients were least informed of the impact of lifestyle changes (38%) and specific cancer treatments (≤35%) on bone health. Sixty-two percent of patients were not completely satisfied with the bone health education received. Patients generally wanted more information (58%) and to receive information by more than one mode of communication. CONCLUSION: Notable gaps in bone health education were observed in cancer patients at risk for SREs indicating an important need for improved communication and education strategies to promote better health outcomes.

Discharge status and post-discharge healthcare costs after skeletal-related event hospitalizations among medicare patients with bone metastatic solid tumors or multiple myeloma.

BACKGROUND: Previous studies have quantified direct inpatient costs of skeletal-related events (SREs); however, costs associated with subsequent post-SRE care have not been examined. METHODS: We identified two study cohorts using 2011-2015 Medicare 20% sample data: patients diagnosed with 1) bone metastases from solid tumors or 2) multiple myeloma (MM), both with SRE-related hospitalization discharge dates January 1, 2011-September 30, 2015. We assessed discharge status and costs from discharge to the earliest of death, end of Medicare enrollment, or December 31, 2015. Discharge status was defined as: skilled nursing facility (SNF), rehabilitation facility, hospice, home health agency (HHA), long-term care (LTC) nursing home, LTC hospital, or rehospitalization within or after 30 days. Percentage, stay duration, and Medicare costs were calculated for each setting. All analyses were descriptive. RESULTS: We identified 7988 bone metastases patients and 4277 MM patients discharged from index SRE-related hospitalizations; corresponding mean ages were 76.9 and 76.6 years. The largest proportion of bone metastases patients were discharged to SNF (32.9%), then HHA (13.7%), hospice (13.5%), and LTC (11.3%); the pattern was similar for MM patients (SNF, 35.9%; HHA, 18.2%; hospice, 7.2%; LTC, 1.5%). Almost 10% of patients in both cohorts were re-hospitalized within 30 days. Mean Medicare cost per patient per facility stay was < $10,000 for hospice, and from $15,517 for LTC nursing home to $49,729 for LTC hospital for MM patients. CONCLUSION: Most elderly cancer patients (>75%) require healthcare facility support after SRE-related hospitalization, with substantial associated costs. Post-discharge management is clinically and economically important.