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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.

ObjectivesTo 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.DesignObservational cohort study.SettingCOVID-19 subset of the Optum deidentified electronic health records, including more than 1.8 million patients from across the USA.ParticipantsThere 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 measuresIncident acute clinical outcomes, including in-hospital all-cause mortality.ResultsRespectively, 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.ConclusionThe 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.

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. 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. 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. 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.

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. 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. 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. 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.

In a randomized trial, solanezumab, a humanized monoclonal antibody against soluble amyloid, did not slow cognitive decline over a period of 80 weeks in patients with mild Alzheimer’s disease and with PET or CSF biomarkers of amyloid-related disease.

Cotranscriptional folding is an obligate step of RNA biogenesis that can guide RNA structure formation and function through transient intermediate folds. This process is particularly important for transcriptional riboswitches in which the formation of ligand-dependent structures during transcription regulates downstream gene expression. However, the intermediate structures that comprise cotranscriptional RNA folding pathways, and the mechanisms that enable transit between them, remain largely unknown. Here, we determine the series of cotranscriptional folds and rearrangements that mediate antitermination by the Clostridium beijerinckii pfl ZTP riboswitch in response to the purine biosynthetic intermediate ZMP. We uncover sequence and structural determinants that modulate an internal RNA strand displacement process and identify biases within natural ZTP riboswitch sequences that promote on-pathway folding. Our findings establish a mechanism for pfl riboswitch antitermination and suggest general strategies by which nascent RNA molecules navigate cotranscriptional folding pathways. The authors characterize the cotranscriptional folding of the Clostridium beijerinckii pfl ZTP riboswitch in response to its ligand ZMP, and reveal that an internal RNA strand displacement and riboswitch sequence play important roles in the process.