Ninety-day and one-year healthcare utilization and costs after knee arthroplasty.

OBJECTIVES: This study examined ninety-day and one-year postoperative healthcare utilization and costs following total knee arthroplasty (TKA) from the health sector and patient perspectives. DESIGN: This study relied on: 1) patient-reported medical resource utilization data from diaries in the Knee Arthroplasty Pain Coping Skills Training (KASTPain) trial; and 2) Medicare fee schedules. Medicare payments, patient cost-sharing, and patient time costs were estimated. Generalized linear mixed models were used to identify baseline predictors of costs. RESULTS: In the first ninety days following TKA, patients had an average of 29.7 outpatient visits and 6% were hospitalized. Mean total costs during this period summed to $3,720, the majority attributed to outpatient visit costs (84%). Over the year following TKA, patients had an average of 48.9 outpatient visits, including 33.2 for physical therapy. About a quarter (24%) of patients were hospitalized. Medical costs were incurred at a decreasing rate, from $2,428 in the first six weeks to $648 in the last six weeks. Mean total medical costs across all patients over the year were $8,930, including $5,328 in outpatient costs. Total costs were positively associated with baseline Charlson comorbidity score (P < 0.01). Outpatient costs were positively associated with baseline Charlson comorbidity score (P = 0.03) and a bodily pain burden summary score (P < 0.01). Mean patient cost-sharing summed to $1,342 and time costs summed to $1,346. CONCLUSIONS: Costs in the ninety days and year after TKA can be substantial for both healthcare payers and patients. These costs should be considered as payers continue to explore alternative payment models.

Model-based pain and function outcome trajectory types for patients undergoing knee arthroplasty: a secondary analysis from a randomized clinical trial.

OBJECTIVE: Knee arthroplasty (KA) is an effective surgical procedure. However, clinical studies suggest that a considerable number of patients continue to experience substantial pain and functional loss following surgical recovery. We aimed to estimate pain and function outcome trajectory types for persons undergoing KA, and to determine the relationship between pain and function trajectory types, and pre-surgery predictors of trajectory types. DESIGN: Participants were 384 patients who took part in the KA Skills Training randomized clinical trial. Pain and function were assessed at 2-week pre- and 2-, 6-, and 12-months post-surgery. Piecewise latent class growth models were used to estimate pain and function trajectories. Pre-surgery variables were used to predict trajectory types. RESULTS: There was strong evidence for two trajectory types, labeled as good and poor, for both Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Function scores. Model estimated rates of the poor trajectory type were 18% for pain and function. Dumenci's latent kappa between pain and function trajectory types was 0.71 (95% CI: 0.61-0.80). Pain catastrophizing and number of painful body regions were significant predictors of poor pain and function outcomes. Outcome-specific predictors included low income for poor pain and baseline pain and younger age for poor function. CONCLUSIONS: Among adults undergoing KA, approximately one-fifth continue to have persistent pain, poor function, or both. Although the poor pain and function trajectory types tend to go together within persons, a significant number experience either poor pain or function but not both, suggesting heterogeneity among persons who do not fully benefit from KA.

Evidence of equine influenza A (H3N8) activity in horses from Eastern and Central Saudi Arabia: 2013-2015.

BACKGROUND: Equine influenza virus (EIV) is one of the main causes of viral respiratory affections in horses. Little is known about the prevalence of EIV in Saudi Arabia especially the H3N8 serotype. OBJECTIVES: To assess prevalence of equine influenza in horse populations in Eastern and Central Saudi Arabia. STUDY DESIGN: Cross-sectional study. METHODS: We collected 145 sera, 323 nasal and 323 rectal swabs from horses from six major cities in Eastern and Central regions. None of the horses were vaccinated against EIV. Sera were tested in ELISA assays for influenza A type-specific antibodies and by haemagglutination inhibition (HI) tests using equine H3N8. The swabs were tested by RT-qPCR assay targeting a conserved region of the influenza A matrix gene that detects influenza A viruses of all subtypes. RESULTS: None of the swabs had detectable influenza A virus RNA. Of the 145 serasamples tested by ELISA, 81 (55.9%) were positive and 98 (67.6%) of 145 sera tested by HI tests were positive for equine H3. MAIN LIMITATIONS: Our failure to detect and sequence any EIV prevents identification of the lineage of virus that circulates in the Kingdom of Saudi Arabia. CONCLUSIONS: These results confirm that EIV H3N8 is circulating in Saudi Arabia and should be considered as a possible cause when investigating horses with respiratory disease in Saudi Arabia.

Appropriateness and total knee arthroplasty: an examination of the American Academy of Orthopaedic Surgeons appropriateness rating system.

OBJECTIVE: The American Academy of Orthopaedic Surgeons (AAOS) recently published appropriateness criteria for patients with knee osteoarthritis (OA) who are being considered for total knee arthroplasty (TKA). We evaluated the extent to which predictor variables used by the AAOS contribute to final classification, rated as "appropriate," "may be appropriate" or "rarely appropriate." METHODS: The RAND/UCLA Appropriateness method was used by AAOS to develop 864 clinical vignettes, each incorporating eight evidence-based variables associated with TKA outcome or need. Variables included function-limiting pain severity, knee OA severity, knee motion and age among others. The contribution of each variable to the overall classification was determined using multinomial regression. A classification tree method was applied to determine the combinations of variables that contributed to final classification for each vignette. RESULTS: Multinomial regression indicated that patient age, knee motion, OA severity and location were the four most powerful predictors of final classification. Function limiting pain, knee instability and lower limb alignment contributed little to the final classification. The classification tree had an accuracy of 86.7% and the most important contributors to classification were age, knee OA severity and pattern. CONCLUSION: Function limiting pain, the most frequent reason endorsed by patients seeking TKA does not meaningfully contribute to the newly developed AAOS appropriateness criteria. The system is highly dependent on traditional variables that surgeons consider when evaluating patients for TKA: patient age, knee OA severity, knee OA pattern and knee motion.

MERS-CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015.

We investigated the kinetics of the Middle East respiratory syndrome coronavirus (MERS-CoV) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription PCR to have been infected during the outbreak in South Korea in 2015. Robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for <1 year. The duration of viral RNA detection (but not viral load) in sputum significantly correlated with the antibody response magnitude. The MERS S1 ELISA antibody titers correlated well with the neutralizing antibody response. Antibody titers in 4 of 6 patients who had mild illness were undetectable even though most had evidence of pneumonia. This finding implies that MERS-CoV seroepidemiologic studies markedly underestimate the extent of mild and asymptomatic infection. Obtaining convalescent-phase plasma with high antibody titers to treat MERS will be challenging.

Coronavirus infections in horses in Saudi Arabia and Oman.

Equine coronaviruses (ECoV) are the only coronavirus known to infect horses. So far, data on ECoV infection in horses remain limited to the USA, France and Japan and its geographic distribution is not well understood. We carried out RT-PCR on 306 nasal and 315 rectal swabs and tested 243 sera for antibodies to detect coronavirus infections in apparently healthy horses in Saudi Arabia and Oman. We document evidence of infection with ECoV and HKU23 coronavirus by RT-PCR. There was no conclusive evidence of Middle East respiratory syndrome coronavirus infection in horses. Serological data suggest that lineage A betacoronavirus infections are commonly infecting horses in Saudi Arabia and Oman but antibody cross-reactivities between these viruses do not permit us to use serological data alone to identify which coronaviruses are causing these infections.

Dromedary Camels and the Transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

Middle East respiratory syndrome coronavirus (MERS-CoV) is an existential threat to global public health. The virus has been repeatedly detected in dromedary camels (Camelus dromedarius). Adult animals in many countries in the Middle East as well as in North and East Africa showed high (>90%) seroprevalence to the virus. Middle East respiratory syndrome coronavirus isolated from dromedaries is genetically and phenotypically similar to viruses from humans. We summarize current understanding of the ecology of MERS-CoV in animals and transmission at the animal-human interface. We review aspects of husbandry, animal movements and trade and the use and consumption of camel dairy and meat products in the Middle East that may be relevant to the epidemiology of MERS. We also highlight the gaps in understanding the transmission of this virus in animals and from animals to humans.

The incident tibiofemoral osteoarthritis with rapid progression phenotype: development and validation of a prognostic prediction rule.

OBJECTIVES: No clinical prediction rules were found for estimating the likelihood of developing incident radiographic tibiofemoral osteoarthritis (OA) with rapid progression. Such a tool would enhance prognostic capability for clinicians and researchers. DESIGN: We used two longitudinal datasets to independently derive (Multicenter Osteoarthritis Study) and validate (Osteoarthritis Initiative) a prognostic clinical prediction rule for estimating the probability of incident rapidly progressing radiographic knee OA in the following 4-5 years. Eligible subjects had at least one knee with a Kellgren and Lawrence (K&L) graded tibiofemoral joint of 0 or 1. Several potential risk factors were examined including obesity, age, knee alignment, frequent knee symptoms, contralateral knee OA and knee injury history. Multiple logistic regression was used to identify significant predictors and area under the receiver operating characteristic curve (AUC) was used to assess discrimination. RESULTS: A total of 1690 subjects participated in the derivation and 2422 subjects participated in the validation of the clinical prediction rule. The multivariable model displayed good discrimination with AUC of 0.79 in the derivation dataset and 0.81 in the validation dataset. CONCLUSIONS: Persons with contralateral knee OA, a baseline index knee OA grade of 1, higher body mass index (BMI) and higher baseline Western Ontario and McMaster Universities arthritis index total scores were more likely to develop K&L grade of 3 or 4 within 5 years. Frequent knee symptoms at baseline were not a significant predictor. The prediction rule and nomogram can assist clinicians in estimating the probability of rapidly progressing radiographic knee OA and the nomogram can assist researchers conducting epidemiologic studies and clinical trials.

Quantifying homologous and heterologous antibody titre rises after influenza virus infection.

Most influenza virus infections are associated with mild disease. One approach to estimate the occurrence of influenza virus infections in individuals is via repeated measurement of humoral antibody titres. We used baseline and convalescent antibody titres measured by haemagglutination inhibition (HI) and viral neutralization (VN) assays against influenza A(H1N1), A(H3N2) and B viruses to investigate the characteristics of antibody rises following virologically confirmed influenza virus infections in participants in a community-based study. Multivariate models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following influenza A virus infections. In 122 participants with PCR-confirmed influenza A virus infection, homologous antibody titres rose by geometric means of 1·2- to 10·2-fold after infection with A(H1N1), A(H3N2) and A(H1N1)pdm09. Significant cross-reactions were observed between A(H1N1)pdm09 and seasonal A(H1N1). Antibody titre rises for some subtypes and assays varied by age, receipt of oseltamivir treatment, and recent receipt of influenza vaccination. In conclusion, we provided a quantitative description of the mean and variation in rises in influenza virus antibody titres following influenza virus infection. The multivariate patterns in boosting of antibody titres following influenza virus infection could be taken into account to improve estimates of cumulative incidence of infection in seroepidemiological studies.

Multivariate analysis of factors affecting the immunogenicity of trivalent inactivated influenza vaccine in school-age children.

We examined factors affecting the immunogenicity of trivalent inactivated influenza vaccination (TIV) in children using the antibody titres of children participating in a Hong Kong community-based study. Antibody titres of strains included in the 2009-2010 northern hemisphere TIV [seasonal A(H1N1), seasonal A(H3N2) and B (Victoria lineage)] and those not included in the TIV [2009 pandemic A(H1N1) and B (Yamagata lineage)] were measured by haemagglutination inhibition immediately before and 1 month after vaccination. Multivariate regression models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following vaccination. Statistically significant rises in geometric mean antibody titres were observed against all strains, with a wide variety of standard deviations and correlations in rises observed, with the influenza type B antibodies showing more variability than the type A antibodies. The dynamics of antibody titres after vaccination can be used in more complex models of antibody dynamics in populations.

Seroepidemiology of Middle East respiratory syndrome (MERS) coronavirus in Saudi Arabia (1993) and Australia (2014) and characterisation of assay specificity.

The pseudoparticle virus neutralisation test (ppNT) and a conventional microneutralisation (MN) assay are specific for detecting antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) when used in seroepidemiological studies in animals. Genetically diverse MERS-CoV appear antigenically similar in MN tests. We confirm that MERS-CoV was circulating in dromedaries in Saudi Arabia in 1993. Preliminary data suggest that feral Australian dromedaries may be free of MERS-CoV but larger confirmatory studies are needed.

Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013.

In Saudi Arabia, including regions of Riyadh and Al Ahsa, pseudoparticle neutralisation (ppNT) and microneutralisation (MNT) tests detected no antibodies to Middle East Respiratory Syndrome coronavirus (MERS-CoV) in sheep (n= 100), goats (n= 45), cattle (n= 50) and chickens (n= 240). Dromedary camels however, had a high prevalence of MERS-CoV antibodies. Bovine coronavirus (BCoV) infected sera from cattle had no cross-reactivity in MERS-CoV ppNT or MNT, while many dromedary camels' sera reacted to both BCoV and MERS-CoV. Some nevertheless displayed specific serologic reaction profiles to MERS-CoV.

Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013.

We describe a novel spike pseudoparticle neutralisation assay (ppNT) for seroepidemiological studies on Middle East respiratory syndrome coronavirus (MERSCoV) and apply this assay together with conventional microneutralisation (MN) tests to investigate 1,343 human and 625 animal sera. The sera were collected in Egypt as a region adjacent to areas where MERS has been described, and in Hong Kong, China as a control region. Sera from dromedary camels had a high prevalence of antibody reactive to MERS-CoV by MERS NT (93.6%) and MERS ppNT (98.2%) assay. The antibody titres ranged up to 1,280 and higher in MN assays and 10,240 and higher in ppNT assays. No other investigated species had any antibody reactivity to MERS-CoV. While seropositivity does not exclude the possibility of infection with a closely related virus, our data highlight the need to attempt detection of MERSCoV or related coronaviruses in dromedary camels. The data show excellent correlation between the conventional MN assay and the novel ppNT assay. The newly developed ppNT assay does not require Biosafety Level 3 containment and is thus a relatively high-throughput assay, well suited for large-scale seroepidemiology studies which are needed to better understand the ecology and epidemiology of MERS-CoV.

Shedding dynamics of Epstein-Barr virus: A type 1 carcinogen.

Epstein Barr virus (EBV) is one of the ubiquitous viral carcinogens found in humans and successfully infects more than 90% of the world population. The spectrum of EBV-related pathology ranges from asymptomatic primary infection to grave B- and T-cell malignancies. EBV triggers lymphoproliferative disorders after allogeneic stem cell transplantation, which contributes to higher mortality rates. Although the transmission of EBV primarily occurs from an infected host to a naive host through viral shedding from the oropharynx, increasing evidence points to considerable amount of shedding in other anatomical sites such as cervix, anal mucosa, breast milk and respiratory tract. It is impossible to eradicate the prevalence of EBV-related malignancies and other pathologies without preventing viral shedding. However, a detail analysis of the multifaceted nature of EBV shedding is not available in the literature. Thus, this review focuses on elucidating the key elements of the shedding dynamics of this carcinogenic virus.