Estimated Incidence of Hospitalizations Attributable to RSV Infection Among Adults in Ontario, Canada, Between 2013 and 2019.

INTRODUCTION: Adult respiratory syncytial virus (RSV) burden is underestimated due to non-specific symptoms, limited standard-of-care and delayed testing, reduced diagnostic test sensitivity-particularly when using single diagnostic specimen-when compared to children, and variable test sensitivity based on the upper airway specimen source. We estimated RSV-attributable hospitalization incidence among adults aged ≥ 18 years in Ontario, Canada, using a retrospective time-series model-based approach. METHODS: The Institute for Clinical Evaluative Sciences data repository provided weekly numbers of hospitalizations (from 2013 to 2019) for respiratory, cardiovascular, and cardiorespiratory disorders. The number of hospitalizations attributable to RSV was estimated using a quasi-Poisson regression model that considered probable overdispersion and was based on periodic and aperiodic time trends and viral activity. As proxies for viral activity, weekly counts of RSV and influenza hospitalizations in children under 2 years and adults aged 60 years and over, respectively, were employed. Models were stratified by age and risk group. RESULTS: In patients ≥ 60 years, RSV-attributable incidence rates were high for cardiorespiratory hospitalizations (range [mean] in 2013-2019: 186-246 [215] per 100,000 person-years, 3‒4% of all cardiorespiratory hospitalizations), and subgroups including respiratory hospitalizations (144-192 [167] per 100,000 person-years, 5‒7% of all respiratory hospitalizations) and cardiovascular hospitalizations (95-126 [110] per 100,000 person-years, 2‒3% of all cardiovascular hospitalizations). RSV-attributable cardiorespiratory hospitalization incidence increased with age, from 14-18 [17] hospitalizations per 100,000 person-years (18-49 years) to 317-411 [362] per 100,000 person-years (≥ 75 years). CONCLUSIONS: Estimated RSV-attributable respiratory hospitalization incidence among people ≥ 60 years in Ontario, Canada, is comparable to other incidence estimates from high-income countries, including model-based and pooled prospective estimates. Recently introduced RSV vaccines could have a substantial public health impact.

RSV Risk Profile in Hospitalized Adults and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

INTRODUCTION: We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60 years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. METHODS: This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission < 30 days) and compared severity between RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. RESULTS: We included 706 RSV patients (635 inpatients and 71 outpatients), and 598 influenza and 60 COVID-19 hospitalized controls with comparable sociodemographic profile. Among RSV patients, 96 (15%) had a subtype identified: 56% A, 42% B, and 2% A + B. Eighty-one percent of RSV patients had cardiovascular conditions, 65% endocrine/metabolic, 46% chronic lung, and 43% immunocompromising conditions. Thirty-six percent were coinfected (vs. 21% influenza and 20% COVID-19; p = < .0001 and 0.01). Ninety-two percent had signs of lower respiratory infection (vs. 85% influenza and 72% COVID-19, p = < .0001) and 27% cardiovascular signs (vs. 20% influenza and 8% COVID-19, p = 0.0031 and 0.0009). Laboratory parameters of anemia, inflammation, and hypoxemia were highest in RSV. Among RSV, being a previous smoker (adjusted OR 2.81 [95% CI 1.01, 7.82]), coinfection (4.34 [2.02, 9.34]), and having cardiovascular (3.79 [2.17, 6.62]), neurologic (2.20 [1.09, 4.46]), or chronic lung (1.93 [1.11, 3.38]) diseases were risks for hospitalization. Being resident in care institutions (1.68 [1.09, 2.61]) or having a coinfection (1.91[1.36, 2.69]) were risks for higher severity, while RSV subtype was not associated with severity. Whereas RSV and influenza patients did not show differences in severity, RSV patients had 68% (38-84%) lower odds of experiencing any severe outcome compared to COVID-19. CONCLUSIONS: RSV especially affects those with comorbidities, coinfections, and living in care institutions. RSV vaccination could have an important public health impact in this population.

Estimation of Symptomatic Respiratory Syncytial Virus Infection Incidence in Adults in Multiple Countries: A Time-Series Model-Based Analysis Protocol.

INTRODUCTION: Estimating respiratory syncytial virus (RSV) burden in adults is challenging because of non-specific symptoms, infrequent standard-of-care testing, resolution of viral shedding before seeking medical care, test positivity that varies by specimen site in the upper airway and lower diagnostic test sensitivity compared to children. Conducting prospective observational studies to assess RSV burden in adults is time- and resource-intensive. Thus, model-based approaches can be applied using existing data to obtain more accurate estimates of RSV burden. This protocol establishes essential elements for estimating RSV incidence rate in adults using a time series model-based approach. It can be tailored to specific databases and applied globally across countries, enabling estimation of local RSV disease burden to inform public health decision-making, including immunization policy. METHODS: Data are analysed using a quasi-Poisson regression model, considering the effect of baseline trends and pathogen co-circulation, stratified by age and risk status. Pathogen co-circulation is represented by viral proxies defined based on ICD code groupings indicating RSV and influenza-specific hospitalizations, lagged 0 up to 4 weeks based on the model selection. A final model is constructed in two steps: optimization of the time trend (using p-values) and selection of the viral proxy lag time (using test statistics, to prioritize the most biologically plausible option). The yearly incidence rate and percentage of events attributable to RSV are estimated from the final model. Confidence intervals are calculated using residual bootstrapping. PLANNED OUTCOMES: Outcomes to be modelled are based on administrative ICD code groupings and include the number of cardiorespiratory, respiratory and cardiovascular events in a specific care setting (e.g., general practitioner visit, emergency department visit, hospitalization and death). Cardiovascular events are limited to those for which existing evidence suggests an association with RSV infection. Additional secondary outcomes are constructed as a subset of the primary outcomes based on specific ICD code groups.

Estimated Incidence of Hospitalizations and Deaths Attributable to Respiratory Syncytial Virus Infections Among Adults in Germany Between 2015 and 2019.

INTRODUCTION: Respiratory syncytial virus (RSV) burden in adults is underestimated mainly due to unspecific symptoms and limited standard-of-care testing. We estimated the population-based incidence of hospitalization and mortality attributable to RSV among adults with and without risk factors in Germany. METHODS: Weekly counts of hospitalizations and deaths for respiratory, cardiovascular, and cardiorespiratory diseases were obtained (Statutory Health Insurance database, 2015-2019). A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends, and viral activity while allowing for potential overdispersion. Weekly counts of RSV and influenza hospitalizations in children < 2 years and adults ≥ 60 years, respectively, were used as viral activity indicators. Models were stratified by age group and risk status (defined as presence of selected comorbidities). RESULTS: Population-based RSV-attributable hospitalization incidence rates were high among adults ≥ 60 years: respiratory hospitalizations (236-363 per 100,000 person-years) and cardiorespiratory hospitalizations (584-912 per 100,000 person-years). RSV accounted for 2-3% of all cardiorespiratory hospitalizations in this age group. The increase in cardiorespiratory hospitalization risk associated with underlying risk factors was greater in 18-44 year old persons (five to sixfold higher) than in ≥ 75 year old persons (two to threefold higher). CONCLUSIONS: This is a first model-based study to comprehensively assess adult RSV burden in Germany. Estimated cardiorespiratory RSV hospitalization rates increased with age and were substantially higher in people with risk factors compared to those without risk factors. Our study indicates that RSV, like other respiratory viruses, contributes to both respiratory and cardiovascular hospitalizations. Effective prevention strategies are needed, especially among older adults ≥ 60 years and among adults with underlying risk factors.

Estimated Respiratory Syncytial Virus-Related Hospitalizations and Deaths Among Children and Adults in Spain, 2016-2019.

INTRODUCTION: Respiratory syncytial virus (RSV) causes a substantial disease burden among infants. In older children and adults, incidence is underestimated due to nonspecific symptoms and limited standard-of-care testing. We aimed to estimate RSV-attributable hospitalizations and deaths in Spain during 2016-2019. METHODS: Nationally representative hospitalization and mortality databases were obtained from the Ministry of Health and the National Statistical Office. A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends and viral activity, while allowing for potential overdispersion. RESULTS: In children, the RSV-attributable respiratory hospitalization incidence was highest among infants aged 0-5 months (3998-5453 cases/100,000 person-years, representing 72% of all respiratory hospitalizations) and decreased with age. In 2019, estimated rates in children 0-5, 6-11, 12-23 months and 6-17 years were approximately 1.3, 1.4, 1.5, and 6.5 times higher than those based on standard-of-care RSV-specific codes. In adults, the RSV-attributable cardiorespiratory hospitalization rate increased with age and was highest among persons ≥ 80 years (1325-1506 cases/100,000, 6.5% of all cardiorespiratory hospitalizations). In 2019, for persons aged 18-49, 50-59, 60-79, and ≥ 80 years, estimated rates were approximately 8, 6, 8, and 16 times higher than those based on standard-of-care RSV-specific codes. The RSV-attributable cardiorespiratory mortality rate was highest among ≥ 80 age group (126-150 deaths/100,000, 3.5-4.1% of all cardiorespiratory deaths), when reported mortality rate ranged between 0 and 0.5/100,000. CONCLUSIONS: When accounting for under-ascertainment, estimated RSV-attributable hospitalizations were higher than those reported based on standard-of-care RSV-specific codes in all age groups but particularly among older children and older adults. Like other respiratory viruses, RSV contributes to both respiratory and cardiovascular complications. Efficacious RSV vaccines could have a high public health impact in these age and risk groups.

Ultra-durable superhydrophobic cellular coatings.

Developing versatile, scalable, and durable coatings that resist the accretion of matters (liquid, vapor, and solid phases) in various operating environments is important to industrial applications, yet has proven challenging. Here, we report a cellular coating that imparts liquid-repellence, vapor-imperviousness, and solid-shedding capabilities without the need for complicated structures and fabrication processes. The key lies in designing basic cells consisting of rigid microshells and releasable nanoseeds, which together serve as a rigid shield and a bridge that chemically bonds with matrix and substrate. The durability and strong resistance to accretion of different matters of our cellular coating are evidenced by strong anti-abrasion, enhanced anti-corrosion against saltwater over 1000 h, and maintaining dry in complicated phase change conditions. The cells can be impregnated into diverse matrixes for facile mass production through scalable spraying. Our strategy provides a generic design blueprint for engineering ultra-durable coatings for a wide range of applications.

Trends in COVID-19 patient characteristics in a large electronic health record database in the United States: A cohort study.

BACKGROUND: Electronic health record (EHR) databases provide an opportunity to facilitate characterization and trends in patients with COVID-19. METHODS: Patients with COVID-19 were identified based on an ICD-10 diagnosis code for COVID-19 (U07.1) and/or a positive SARS-CoV-2 viral lab result from January 2020 to November 2020. Patients were characterized in terms of demographics, healthcare utilization, clinical comorbidities, therapies, laboratory results, and procedures/care received, including critical care, intubation/ventilation, and occurrence of death were described, overall and by month. RESULTS: There were 393,773 patients with COVID-19 and 56,996 with a COVID-19 associated hospitalization. A greater percentage of patients hospitalized with COVID-19 relative to all COVID-19 cases were older, male, African American, and lived in the Northeast and South. The most common comorbidities before admission/infection date were hypertension (40.8%), diabetes (29.5%), and obesity (23.8%), and the most common diagnoses during hospitalization were pneumonia (59.6%), acute respiratory failure (44.8%), and dyspnea (28.0%). A total of 85.7% of patients hospitalized with COVID-19 had CRP values > 10 mg/L, 75.5% had fibrinogen values > 400 mg/dL, and 76.8% had D-dimer values > 250 ng/mL. Median values for platelets, CRP, lactate dehydrogenase, D-dimer, and fibrinogen tended to decrease from January-March to November. The use of chloroquine/hydroxychloroquine during hospitalization peaked by March (71.2%) and was used rarely by May (5.1%) and less than 1% afterwards, while the use of remdesivir had increased by May (10.0%) followed by dexamethasone by June (27.7%). All-cause mortality was 3.2% overall and 15.0% among those hospitalized; 21.0% received critical care and 16.0% received intubation/ventilation/ECMO. CONCLUSIONS: This study characterizes US patients with COVID-19 and their management during hospitalization over the first eleven months of this disease pandemic.

Predictors of critical care, mechanical ventilation, and mortality among hospitalized patients with COVID-19 in an electronic health record database.

BACKGROUND: There are limited data on risk factors for serious outcomes and death from COVID-19 among patients representative of the U.S. POPULATION: The objective of this study was to determine risk factors for critical care, ventilation, and death among hospitalized patients with COVID-19. METHODS: This was a cohort study using data from Optum's longitudinal COVID-19 electronic health record database derived from a network of healthcare provider organizations across the US. The study included patients with confirmed COVID-19 (presence of ICD-10-CM code U07.1 and/or positive SARS-CoV-2 test) between January 2020 and November 2020. Patient characteristics and clinical variables at start of hospitalization were evaluated for their association with subsequent serious outcomes (critical care, mechanical ventilation, and death) using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression, adjusted for demographic variables. RESULTS: Among 56,996 hospitalized COVID-19 patients (49.5% male and 72.4% ≥ 50 years), 11,967 received critical care, 9136 received mechanical ventilation, and 8526 died. The median duration of hospitalization was 6 days (IQR: 4, 11), and this was longer among patients that experienced an outcome: 11 days (IQR: 6, 19) for critical care, 15 days (IQR: 8, 24) for mechanical ventilation, and 10 days (IQR: 5, 17) for death. Dyspnea and hypoxemia were the most prevalent symptoms and both were associated with serious outcomes in adjusted models. Additionally, temperature, C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, and oxygen saturation measured during hospitalization were predictors of serious outcomes as were several in-hospital diagnoses. The strongest associations were observed for acute respiratory failure (critical care: OR, 6.30; 95% CI, 5.99-6.63; ventilation: OR, 8.55; 95% CI, 8.02-9.11; death: OR, 3.36; 95% CI, 3.17-3.55) and sepsis (critical care: OR, 4.59; 95% CI, 4.39-4.81; ventilation: OR, 5.26; 95% CI, 5.00-5.53; death: OR, 4.14; 95% CI, 3.92-4.38). Treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers during hospitalization were inversely associated with death (OR, 0.57; 95% CI, 0.54-0.61). CONCLUSIONS: We identified several clinical characteristics associated with receipt of critical care, mechanical ventilation, and death among COVID-19 patients. Future studies into the mechanisms that lead to severe COVID-19 disease are warranted.

Measuring problem prescription opioid use among patients receiving long-term opioid analgesic treatment: development and evaluation of an algorithm for use in EHR and claims data.

Objective: Opioid surveillance in response to the opioid epidemic will benefit from scalable, automated algorithms for identifying patients with clinically documented signs of problem prescription opioid use. Existing algorithms lack accuracy. We sought to develop a high-sensitivity, high-specificity classification algorithm based on widely available structured health data to identify patients receiving chronic extended-release/long-acting (ER/LA) therapy with evidence of problem use to support subsequent epidemiologic investigations. Methods: Outpatient medical records of a probability sample of 2,000 Kaiser Permanente Washington patients receiving ≥60 days' supply of ER/LA opioids in a 90-day period from 1 January 2006 to 30 June 2015 were manually reviewed to determine the presence of clinically documented signs of problem use and used as a reference standard for algorithm development. Using 1,400 patients as training data, we constructed candidate predictors from demographic, enrollment, encounter, diagnosis, procedure, and medication data extracted from medical claims records or the equivalent from electronic health record (EHR) systems, and we used adaptive least absolute shrinkage and selection operator (LASSO) regression to develop a model. We evaluated this model in a comparable 600-patient validation set. We compared this model to ICD-9 diagnostic codes for opioid abuse, dependence, and poisoning. This study was registered with ClinicalTrials.gov as study NCT02667262 on 28 January 2016. Results: We operationalized 1,126 potential predictors characterizing patient demographics, procedures, diagnoses, timing, dose, and location of medication dispensing. The final model incorporating 53 predictors had a sensitivity of 0.582 at positive predictive value (PPV) of 0.572. ICD-9 codes for opioid abuse, dependence, and poisoning had a sensitivity of 0.390 at PPV of 0.599 in the same cohort. Conclusions: Scalable methods using widely available structured EHR/claims data to accurately identify problem opioid use among patients receiving long-term ER/LA therapy were unsuccessful. This approach may be useful for identifying patients needing clinical evaluation.

Identifying and classifying opioid-related overdoses: A validation study.

PURPOSE: The study aims to develop and validate algorithms to identify and classify opioid overdoses using claims and other coded data, and clinical text extracted from electronic health records using natural language processing (NLP). METHODS: Primary data were derived from Kaiser Permanente Northwest (2008-2014), an integrated health care system (~n > 475 000 unique individuals per year). Data included International Classification of Diseases, Ninth Revision (ICD-9) codes for nonfatal diagnoses, International Classification of Diseases, Tenth Revision (ICD-10) codes for fatal events, clinical notes, and prescription medication records. We assessed sensitivity, specificity, positive predictive value, and negative predictive value for algorithms relative to medical chart review and conducted assessments of algorithm portability in Kaiser Permanente Washington, Tennessee State Medicaid, and Optum. RESULTS: Code-based algorithm performance was excellent for opioid-related overdoses (sensitivity = 97.2%, specificity = 84.6%) and classification of heroin-involved overdoses (sensitivity = 91.8%, specificity = 99.0%). Performance was acceptable for code-based suicide/suicide attempt classifications (sensitivity = 70.7%, specificity = 90.5%); sensitivity improved with NLP (sensitivity = 78.7%, specificity = 91.0%). Performance was acceptable for the code-based substance abuse-involved classification (sensitivity = 75.3%, specificity = 79.5%); sensitivity improved with the NLP-enhanced algorithm (sensitivity = 80.5%, specificity = 76.3%). The opioid-related overdose algorithm performed well across portability assessment sites, with sensitivity greater than 96% and specificity greater than 84%. Cross-site sensitivity for heroin-involved overdose was greater than 87%, specificity greater than or equal to 99%. CONCLUSIONS: Code-based algorithms developed to detect opioid-related overdoses and classify them according to heroin involvement perform well. Algorithms for classifying suicides/attempts and abuse-related opioid overdoses perform adequately for use for research, particularly given the complexity of classifying such overdoses. The NLP-enhanced algorithms for suicides/suicide attempts and abuse-related overdoses perform significantly better than code-based algorithms and are appropriate for use in settings that have data and capacity to use NLP.

Exenatide use and incidence of pancreatic and thyroid cancer: A retrospective cohort study.

A retrospective cohort study, supplemented with a nested case-control study, was performed using two administrative databases from commercial health plans in the United States to compare the incidence of pancreatic and thyroid cancer among users of exenatide versus other antidiabetic drugs (OADs). Patients with type 2 diabetes who initiated exenatide or OADs between 1 June 2005 and 30 June 2015 were included. Pancreatic and thyroid cancers were identified using chart-validated algorithms in the cohort study. Cases in the nested case-control study were chart-confirmed pancreatic or thyroid cancers, and controls were sampled using risk-set sampling. The time-fixed analyses comparing 33 629 exenatide initiators with 49 317 propensity-score-matched OAD initiators yielded hazard ratios of 0.76 (95% confidence interval [CI] 0.47-1.21) for pancreatic cancer and 1.46 (95% CI 0.98-2.19) for thyroid cancer. Results in the time-dependent analyses by cumulative duration or dose were similar. Nested case-control analyses yielded rate ratios of 0.61 (95%CI, 0.37-1.00) for pancreatic cancer and 0.89 (95% CI, 0.64-1.24) for thyroid cancer. This observational study suggested exenatide use was not associated with an increased risk of pancreatic or thyroid cancer.

Beetle-like droplet-jumping superamphiphobic coatings for enhancing fog collection of sheet arrays.

Fog collection from atmosphere is an effective way to solve the water resource crisis in arid or semi-arid areas. Inspired by the bumpy surface of the desert beetle, this work provides a beetle-like superamphiphobic coating by adding silicon carbide particles to nano-SiO2 superamphiphobic coating in proportion, which shows excellent superamphiphobic performance, high nucleation rate, efficient drop removal efficiency and recommendable fog collection effect. In this work, drop removal is facilitated by the collisions of water droplets between the array sheets, and when the as-prepared samples are placed parallel to each other and with a space of ∼2 mm, the jumping drop collisions between two sample surfaces could promote the departure of droplets, and the water collection rate of the collision surface increased by ∼217% compared to that of the non-collision surface, which provides a new idea to promote water droplet removal. This work findings are instrumental in water collection and have wide application prospects in desalination, heat transfer, anti-fogging and other fields.

Frosting Behavior of Superhydrophobic Nanoarrays under Ultralow Temperature.

Retarding and preventing frost formation at ultralow temperature has an increasing importance due to a wide range of applications of ultralow fluids in aerospace and industrial facilities. Recent efforts for developing antifrosting surfaces have been mostly devoted to utilizing lotus-leaf-inspired superhydrophobic surfaces. Whether the antifrosting performance of the superhydrophobic surface is still effective under ultralow temperature has not been elucidated clearly. Here, we investigated the frosting behavior of fabricated superhydrophobic ZnO nanoarrays under different temperature and different environment. The surface showed excellent performance in anticondensation and antifrosting when the surface temperature was approximately -20 °C. Although the frosting event inevitably occurs on all surfaces when the temperature is decreased from -50 to -150 °C, the frost accumulation on the superhydrophobic surfaces is always less than that on the untreated surfaces. Interestingly, the frost layer detaches from the surface within a short time and keeps the surface dry in the very beginning of the defrosting process. Further, there is no frost formation on the surface at -20 °C during 10 min testing when blowing compressed air and spraying methanol together or spraying methanol individually. It can reduce the height of the frost layer and increases the density when spraying methanol at -150 °C. Furthermore, the frost crystals on the top surface can been blown away due to the low adhesion of ice or frost. It provides a basic idea for solving the frosting problem under ultralow temperature while combined with other defrosting methods.

Sprayable superhydrophobic nano-chains coating with continuous self-jumping of dew and melting frost.

Spontaneous movement of condensed matter provides a new insight to efficiently improve condensation heat transfer on superhydrophobic surface. However, very few reports have shown the jumping behaviors on the sprayable superhydrophobic coatings. Here, we developed a sprayable silica nano-porous coating assembled by fluorinated nano-chains to survey the condensates' dynamics. The dewdrops were continuously removed by self- and/or trigger-propelling motion due to abundant nano-pores from random multilayer stacking of nano-chains. In comparison, the dewdrops just could be slipped under the gravity effect on lack of nano-pores coatings stacked by silica nano-spheres and nano-aggregates. More interestingly, the spontaneous jumping effect also occurred on micro-scale frost crystals under the defrosting process on nano-chains coating surfaces. Different from self-jumping of dewdrops motion, the propelling force of frost crystals were provided by a sudden increase of the pressure under the frost crystal.

Implications of immortal person-time when outcomes are nonfatal.

PURPOSE: The amount of immortal time bias in studies with nonfatal outcomes is unclear. To quantify the magnitude of bias from mishandling of immortal person-time in studies of nonfatal outcomes. METHODS: We derived formulas for quantifying bias from misclassified or excluded immortal person-time in settings with nonfatal outcomes, assuming a constant rate of outcome. In the situation of misclassified or excluded immortal person-time, the quantification includes the immortal time and corresponding events mistakenly attributed to the exposed group (misclassified) or excluded from study (excluded) that must be attributed to the comparison group. RESULTS: With misclassified immortal person-time, the magnitude of bias varies according to the incidence rate ratio of immortal time and comparison group as well as the rate ratio of immortal time and exposed group: toward null for both ratios less than 1, no bias for both ratios equal to 1, away from null for both ratios greater than 1. For one ratio less than 1 and the other greater than 1, the direction and magnitude of bias can be obtained from the formula provided. With excluded immortal person-time, the magnitude of bias is associated with the incidence rate ratio of immortal time and comparison group: toward null for the ratio less than 1, no bias for the ratio equal to 1, and away from null for the ratio greater than 1. CONCLUSIONS: Bias due to immortal person-time in studies with nonfatal outcomes can vary widely and can be quantified under assumptions that apply to many studies.

The treatment patterns, efficacy, and safety of nab (®)-paclitaxel for the treatment of metastatic breast cancer in the United States: results from health insurance claims analysis.

BACKGROUND: nab-Paclitaxel is an albumin-bound formulation of paclitaxel approved for the treatment of metastatic breast cancer (MBC). This analysis was designed to characterize the treatment patterns, efficacy, and safety of nab-paclitaxel for MBC treatment using health claims data from US health plans associated with Optum. METHODS: Women aged ≥ 18 years who initiated nab-paclitaxel for MBC treatment from January 1, 2005, to September 30, 2012, and who met eligibility criteria were selected from the Optum Research Database for this analysis. Patients were required to have complete medical coverage and pharmacy benefits, ≥ 6 months of continuous enrollment, and a diagnosis of MBC prior to nab-paclitaxel initiation. The pattern of use for nab-paclitaxel (eg, regimen, schedule, duration, and administration) and claims-captured toxicities were characterized by line of therapy. Overall survival (OS) and time to next therapy or death (TNTD) were described by line of therapy, regimen, and schedule. RESULTS: Of the 664 nab-paclitaxel patients, 172 (25.9%) received it as first-line therapy, 211 (31.8%) as second-line therapy, and 281 (42.3%) as third-line or later therapy. Overall, the majority of patients received monotherapy (61%) and followed a weekly (71%) rather than an every 3 weeks treatment schedule. nab-Paclitaxel was often (31.7%) combined with targeted therapy (57.5% with bevacizumab and 23.9% with trastuzumab or lapatinib). The median duration of therapy was 128 days (4.2 months). For the overall population, median OS was 17.4 months (22.7, 17.4, and 15.1 months in first-, second-, and third-line or later therapy, respectively). Median TNTD was 6.1 months (7.1, 6.6, and 5.3 months in first-, second-, and third-line or later therapy, respectively). For patients aged ≤ 50 years or with ≥ 3 metastatic sites, median OS was 15.6 months. No new safety signal was identified. CONCLUSIONS: In this US healthcare system, the majority of patients received nab-paclitaxel as second-line or later therapy, monotherapy, and weekly treatment. The efficacy and safety outcomes of nab-paclitaxel observed in this real-world setting appear consistent with those from clinical trial data.

Progression of autosomal dominant kidney disease: measurement of the stage transitions of chronic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. METHODS: This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000-2/28/2013 and ≥6 months of previous continuous enrollment (baseline) within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD) patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. RESULTS: ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. CONCLUSIONS: These results suggest that distribution of patients by age at transition to next stage may be useful for identification of ADPKD patients at risk of rapid progression. The results also suggest that medical claims with diagnosis codes for "unspecified PKD", in absence of a diagnosis code for autosomal recessive polycystic kidney disease, may be a good proxy for ADPKD.

A coding variant in TMC8 (EVER2) is associated with high risk HPV infection and head and neck cancer risk.

HPV infection is a causal agent in many epithelial cancers, yet our understanding of genetic susceptibility to HPV infection and resultant cancer risk is limited. Epidermodysplasia Verruciformis is a rare condition of extreme susceptibility to cutaneous HPV infection primarily attributable to mutations in TMC6 and TMC8. Genetic variation in the TMC6/TMC8 region has been linked to beta-type HPV infection and squamous cell carcinoma of the skin, cervical cancer, HPV persistence and progression to cervical cancer. Here, we have tested the hypothesis that the common TMC8 SNP rs7208422 is associated with high-risk HPV infection and risk of head and neck squamous cell carcinoma (HNSCC). Seropositivity to the HPV L1 protein (HPV16, 18, 11, 31, 33, 35, 45, 52, 58) was measured in 514 cases and 452 population-based controls. Genotype was significantly associated with seropositivity to HPV18 L1 (OR TT vs AA = 0.48, 95% CI = 0.22-0.99) and borderline significantly associated with HPV16 L1 (OR TT vs AA = 0.58, 95% CI = 0.22-1.17). There was a consistent inverse association between TMC8 genotype and infection with other HPV types, including statistically significant associations for HPV31 and HPV52. Consistent with these results, the variant T genotype was associated with a reduced risk of HNSCC (ORAT: 0.63, 95% CI 0.45-0.89, ORTT: 0.54, 95% CI 0.36-0.81), even among subjects seronegative for all HPV types (ORAT: 0.71, 95% CI 0.45-1.11, ORTT: 0.54, 95% CI 0.31-0.93). Our data indicate that common genetic variation in TMC8 is associated with high-risk HPV infection and HNSCC etiology.

Cardiac mortality in users of olmesartan, other angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors.

PURPOSE: Clinical trials of olmesartan for prevention of progression of renal disease in patients with diabetes showed renal protection but an unexpected imbalance in cardiac deaths. The US Food and Drug Administration requested from the manufacturer a cohort study of olmesartan, other angiotensin-receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors in a large population. METHODS: A retrospective cohort study was conducted with the cooperation of a US health insurer. Subject entry and follow-up ran from 2002 through 2009. In propensity-matched cohorts, the primary analysis considered continuous current users. Endpoints were sudden cardiac death (SCD) and all-cause mortality, identified through the US National Death Index, supplemented by insurance and hospital discharge data. Statistical estimation was based on proportional hazards analyses with 95% confidence intervals. Power calculations had shown that 25,000 olmesartan initiators would be required to detect relative risks (RRs) of SCD of twofold or greater. RESULTS: A total of 57,123 initiators of olmesartan were matched 1:2 to initiators of other ARBs and 41,801 to initiators of ACE inhibitors. Average follow-up time ranged from 8 to 9 months. Olmesartan initiators and comparators experienced similar patterns of both outcomes, with RRs ≤1.0 and upper confidence bounds ≤1.6. Among persons with prior use of hypoglycemic agents, in comparison with other ARBs, the RR of SCD for olmesartan users was 0.8, with an upper confidence bound of 2.2. CONCLUSION: The results of this well-powered study do not raise concerns for the risk of SCD or death from all causes among olmesartan users in comparison with users of other ARBs or ACE inhibitors.

Biomarkers of HPV in head and neck squamous cell carcinoma.

Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.