Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation.

PURPOSE: A series of iterative population pharmacokinetic (PK) modeling and probability of target attainment (PTA) analyses based on emerging data supported dose selection for aztreonam-avibactam, an investigational combination antibiotic for serious Gram-negative bacterial infections. METHODS: Two iterations of PK models built from avibactam data in infected patients and aztreonam data in healthy subjects with "patient-like" assumptions were used in joint PTA analyses (primary target: aztreonam 60% fT > 8 mg/L, avibactam 50% fT > 2.5 mg/L) exploring patient variability, infusion durations, and adjustments for moderate (estimated creatinine clearance [CrCL] > 30 to ≤ 50 mL/min) and severe renal impairment (> 15 to ≤ 30 mL/min). Achievement of > 90% joint PTA and the impact of differential renal clearance were considerations in dose selection. RESULTS: Iteration 1 simulations for Phase I/IIa dose selection/modification demonstrated that 3-h and continuous infusions provide comparable PTA; avibactam dose drives joint PTA within clinically relevant exposure targets; and loading doses support more rapid joint target attainment. An aztreonam/avibactam 500/137 mg 30-min loading dose and 1500/410 mg 3-h maintenance infusions q6h were selected for further evaluation. Iteration 2 simulations using expanded PK models supported an alteration to the regimen (500/167 mg loading; 1500/500 mg q6h maintenance 3-h infusions for CrCL > 50 mL/min) and selection of doses for renal impairment for Phase IIa/III clinical studies. CONCLUSION: A loading dose plus 3-h maintenance infusions of aztreonam-avibactam in a 3:1 fixed ratio q6h optimizes joint PTA. These analyses supported dose selection for the aztreonam-avibactam Phase III clinical program. CLINICAL TRIAL REGISTRATION: NCT01689207; NCT02655419; NCT03329092; NCT03580044.

Referring and Specialist Physician Gender and Specialist Billing.

Importance: While a gender pay gap in medicine has been well documented, relatively little research has addressed mechanisms that mediate gender differences in referral income for specialists. Objective: To examine gender-based disparities in medical and surgical specialist referrals in Ontario, Canada. Design, Setting, and Participants: This cross-sectional study included referrals for specialist care ascertained from Ontario Health Insurance Plan physician billings for fiscal year 2018 to 2019. Participants were specialist physicians who received new patient consultations from April 1, 2018, to March 31, 2019, and the associated referring physicians. Data were analyzed from April 2018 to March 2020, including a 12-month follow-up period. Exposures: Specialist and referring physician gender (female or male). Main Outcomes and Measures: Revenue per referral was defined based on an episode-of-care approach as total billings for a 12-month period from the initial consultation. Mean total billings for female and male specialists were compared and the differential divided into the portion owing to referral volume vs referral revenue. Difference-in-differences multivariable regression analysis was used to estimate gender-based differences in revenue per referral. For each referring physician, gender-based differences in referral patterns were examined using case-control analysis, in which specialists who received a referral were compared with matched control specialists who did not receive a referral. This analysis considered the gender of the specialist and concordance between the gender of the referring physician and specialist, among other characteristics. Results: Of 7 621 365 new referrals, 32 824 referring physicians, of whom 13 512 (41.2%) were female (mean [SD] age, 46.3 [11.6] years) and 19 312 (58.8%) were male (mean [SD] age, 52.9 [13.5] years), made referrals to 13 582 specialists, of whom 4890 (36.0%) were female (mean [SD] age, 45.6 [11.0] years) and 8692 (64.0%) were male (mean [SD] age, 51.8 [13.0] years). Male specialists received more mean (SD) referrals than did female specialists (633 [666] vs 433 [515]), and the mean (SD) revenue per referral was higher for males ($350 [$474]) compared with females ($316 [$393]). Adjusted analysis demonstrated a -4.7% (95% CI, -4.9% to -4.5%) difference in the revenue per referral between male and female specialists. Multivariable regression analysis found that physicians referred more often to specialists of the same gender (odds ratio, 1.04; 95% CI, 1.03-1.04) but had higher odds of referring to male specialists (odds ratio, 1.10; 95% CI, 1.09-1.11). Conclusions and Relevance: In this cross-sectional study of the gender pay gap in specialist referral income, the number and revenue from referrals received differed by gender, as did the odds of receiving a referral from a physician of the same gender. Future research should examine the effectiveness of different policies to address this gap, such as a centralized, gender-blinded referral system.

Technostress as source of physician burnout: An exploration of the associations between technology usage and physician burnout.

BACKGROUND: The cause of physician burnout is multifactorial. Health care systems pressures, excessive workloads, fatigue, poor self-care, administrative burdens, work hours, technological advancements, and work-home life conflicts, are all prominent themes throughout the literature. To date, little is known about whether, and to what extent, stressors related to the use of information and communication technology (ICT) use, other than electronic health records, outside of working hours, contribute to physician burnout. PURPOSE: The purpose of this study was to explore whether work related ICT use outside of working hours is associated with physician burnout. METHOD: A cross-sectional survey delivered online using The Maslach Burnout Inventory (MBI), a Physician Technology Usage Scale (PTUS) (and 7 personal characteristics questions. Data were analyzed using bivariate correlations, analysis of variance (ANOVA) and t-tests, and multiple linear regression. RESULTS: Of 2,108 participants invited to complete the survey, 403 responded to and completed the survey (19% response rate). Results identified two significant factors associated with physician burnout: work related technology use outside of working hours, and the number of years in practice. CONCLUSION: This research highlights the need for additional in-depth research into areas such as: 1. work-home life issues and how the use of technology outside of work hours may affect or be affected by burnout; 2. physician age and experience and burnout; 3. The differences between specialties and whether and how specialty-specific factors are related to burnout.

Association between virtual primary care and emergency department use during the first year of the COVID-19 pandemic in Ontario, Canada.

BACKGROUND: Uptake of virtual care increased substantially during the first year of the COVID-19 pandemic. The aim of this study was to evaluate whether a shift from in-person to virtual visits by primary care physicians was associated with increased use of emergency departments among their enrolled patients. METHODS: We conducted an observational study of monthly virtual visits and emergency department visits from Apr. 1, 2020, to Mar. 31, 2021, using administrative data from Ontario, Canada. We used multivariable regression analysis to estimate the association between the proportion of a physician's visits that were delivered virtually and the number of emergency department visits among their enrolled patients. RESULTS: The proportion of virtual visits was higher among female, younger and urban physicians, and the number of emergency department visits was lower among patients of female and urban physicians. In an unadjusted analysis, a 1% increase in a physician's proportion of virtual visits was found to be associated with 11.0 (95% confidence interval [CI] 10.1-11.8) fewer emergency department visits per 1000 rostered patients. After controlling for covariates, we observed no statistically significant change in emergency department visits per 1% increase in the proportion of virtual visits (0.2, 95% CI -0.5 to 0.9). INTERPRETATION: We did not find evidence that patients substituted emergency department visits in the context of decreased availability of in-person care with their family physician during the first year of the COVID-19 pandemic. Future research should focus on the long-term impact of virtual care on access and quality of patient care.

COVID-19 and the duration of operating room procedures in Ontario: a population-based retrospective study.

BACKGROUND: Studies have estimated that a large backlog of procedures was generated by emergency measures implemented in Ontario, Canada, at the onset of the COVID-19 pandemic, when nonessential and scheduled procedures were postponed. Understanding the impact of the COVID-19 pandemic on the time needed to perform a procedure may help to determine the resources needed to tackle the substantial backlog caused by the deferral of cases. The purpose of this study was to examine the duration of operating room (OR) procedures before and after the onset of the COVID-19 pandemic to inform planning around changes in required resources. METHODS: A population-based, retrospective cohort study was conducted using Ontario Health Insurance Plan claims data and other administrative health care data from Apr. 1, 2019, to Sept. 30, 2020. Statistical analysis was conducted using multivariate regression, with procedure duration as the outcome variable. RESULTS: Results showed that the average duration of nonelective procedures increased by 34 minutes during the COVID-19 period and by 19 minutes after the resumption of scheduled procedures. Controlling for physician, patient and hospital characteristics, and the procedure code submitted, procedure duration increased by 12 minutes in the nonelective COVID-19 period and by 5 minutes when scheduled procedures resumed, compared with the pre-COVID-19 period. CONCLUSION: Procedures may take longer in the COVID-19 period. This will affect wait times, which had already increased because of the deferral of procedures at the beginning of the pandemic, and will have an impact on Ontario's ability to provide patients with timely care.

Impact of the COVID-19 pandemic upon self-reported physician burnout in Ontario, Canada: evidence from a repeated cross-sectional survey.

OBJECTIVES: To estimate the impact of the SARS-CoV-2 (COVID-19) pandemic on levels of burnout among physicians in Ontario, Canada, and to understand physician perceptions of the contributors and solutions to burnout. DESIGN: Repeated cross-sectional survey. SETTING: Active and retired physicians, residents and medical students in Canada's largest province were invited to participate in an online survey via an email newsletter. PARTICIPANTS: In the first survey wave (March 2020), 1400 members responded (representing 76.3% of those who could be confirmed to have received the survey and 3.1% of total membership). In the second wave (March 2021), 2638 responded (75.9% of confirmed survey recipients and 5.8% of membership). KEY OUTCOME MEASURE: Level of burnout was assessed using a validated, single-item, self-defined burnout measure where options ranged from 1 (no symptoms of burnout) to 5 (completely burned out). RESULTS: The overall rate of high levels of burnout (self-reported levels 4-5) increased from 28.0% in 2020 (99% CI: 24.3% to 31.7%) to 34.7% in 2021 (99% CI: 31.8% to 37.7%), a 1-year increase of 6.8 percentage points (p<0.01). After a full year of practising during the COVID-19 pandemic, respondents ranked 'patient expectations/patient accountability', 'reporting and administrative obligations' and 'practice environment' as the three factors that contributed most to burnout. Respondents ranked 'streamline and reduce required documentation/administrative work', 'provide fair compensation' and 'improve work-life balance' as the three most important solutions. CONCLUSIONS: During the first 12 months of the COVID-19 pandemic in Ontario, prevalence of high levels of burnout had significantly increased. The contributors and solutions ranked highest by physicians were system-level or organisational in nature.

Surgical wait times and socioeconomic status in a public healthcare system: a retrospective analysis.

BACKGROUND: One aim of publicly-funded health care systems is to provide equitable access to care irrespective of ability to pay. At the same time, differences in socioeconomic status (SES) are associated with health outcomes and access to care, including waiting times for surgery. In public systems where both high- and low-SES patients use the same resources, low-SES patients may be adversely impacted in surgical waiting times. The purpose of this study was to determine whether a publicly-funded health system can provide equitable access to surgical care across socioeconomic status. METHODS: Patient-level records were obtained from a comprehensive provincially-administered surgical wait time database, encompassing years 2006-2015 and 98% of Ontario hospitals. Patient SES was determined by linking postal code with the Material and Social Deprivation Index. Surgical waiting times (time in days between decision to treat and surgery) accounted for patient-initiated delays in treatment, and regression analysis considered age, SES, rurality, sex, priority level for surgical urgency (assigned by surgeons), surgical subspecialty, number of visits, and procedure year. RESULTS: For the 4,253,305 surgical episodes, the mean wait time was 62.3 (SD 75.4) days. Repeated measures least squares regression analysis showed the least deprived SES quintile waited 3 days longer than the most deprived quintile. Wait times dropped in the initial study period but then increased. The proportion of procedures exceeding wait time access targets remained low at 11-13%. CONCLUSIONS: The least deprived SES quintile waited the longest, although the absolute difference was small. This study demonstrates that publicly-funded healthcare systems can provide equitable access to surgical care across SES.

Disparities in Physician Compensation by Gender in Ontario, Canada.

Importance: Men and women should earn equal pay for equal work. An examination of the magnitude of pay disparities could inform strategies for remediation. Objective: To examine gender-based differences in pay within a large, comprehensive physician population practicing within a variety of payment systems. Design, Setting, and Participants: This cross-sectional study used data from the Ontario Health Insurance Plan (OHIP) in the 2017 to 2018 fiscal year to estimate differences in gross payments between men and women physicians in Ontario, Canada. Pay gaps were calculated annually and daily. Regression analyses were used to control for observable practice characteristics that could account for individual differences in daily pay. In Canada's largest province, Ontario, medical services are predominantly provided by self-employed physicians who bill the province's single payer, OHIP. All physicians who submitted claims to OHIP were included. Data were analyzed from January 2020 to July 2021. Exposures: Physician gender, obtained from the OHIP Corporate Provider Database. Gender is recorded as male or female. Main Outcomes and Measures: Gross clinical payments were tabulated for individual physicians on a daily and annual basis in conjunction with each physician's practice characteristics, setting, and specialty. Results: A total of 31 481 physicians were included in the study sample (12 604 [40.0%] women; 18 877 [60.0%] men; mean [SD] time since graduation, 23.3 [13.6] years), representing 99% of active physicians in Ontario. The unadjusted differences in clinical payments between male and female physicians were 32.8% (95% CI, 30.8%-34.6%) annually and 22.5% (95% CI, 21.2%-23.8%) daily. After accounting for practice characteristics, region, and specialty, the overall daily payment gap was 13.5% (95% CI, 12.3%-14.8%). The pay gap persisted with differing magnitudes when examined by specialty (ranging from 6.6% to 37.6%), practice setting (8.3% to 17.2%), payment model (13.4% to 22.8% for family medicine; 8.0% to 11.6% for other specialties), and rurality (8.0% to 16.5%). Conclusions and Relevance: This cross-sectional study examined differences in magnitude of annual and daily payment gaps and between unadjusted and adjusted gaps. Comparing the gaps for different specialties, geography, and payment systems illustrated the complexity of the issue by showing that the pay gap varied for physicians in different practice settings. As such, multiple directed interventions will be necessary to ensure that all physicians are paid equally for equal work, regardless of gender.

Putting the Patient First: A Scoping Review of Patient Desires in Canada.

Patient-centred care is a key priority for governments, providers and stakeholders, yet little is known about the care preferences of patient groups. We completed a scoping review that yielded 193 articles for analysis. Five health states were used to account for the diversity of possible preferences based on health needs. Five broad themes were identified and expressed differently across the health states, including personalized care, navigation, choice, holistic care and care continuity. Patients' perspectives must be considered to meet the diverse needs of targeted patient groups, which can inform health system planning, quality improvement initiatives and targeting of investments.

Adoption of a laboratory EMR system and inappropriate laboratory testing in Ontario: a cross-sectional observational study.

BACKGROUND: Electronic medical record (EMR) systems have the potential to facilitate appropriate laboratory testing. We examined three common medical tests in primary care-hemoglobin A1c (HbA1c), lipid, and thyroid stimulating hormone (TSH)- to assess whether adoption of a laboratory EMR system in Ontario had an impact on the rate of inappropriate testing among primary care physicians. METHODS: We used FY2016-17 population-level laboratory data to estimate the association between adoption of a laboratory EMR system and the rate of inappropriate testing. Inappropriate testing was assessed based on recommendations for screening, monitoring, and follow-up that take into account risk factors related to patient age and certain clinical conditions. To overcome the problem of potential endogeneity of physician choice to use the EMR, the EMR penetration rate in the physician's geographical area of practice was used as an instrumental variable in an ordinary least squares (OLS) regression. We then simulated the change in the rate of inappropriate testing, by physician payment model, as the EMR penetration rate increased from the baseline percentage. RESULTS: The simulation models showed that an increase in the rate of EMR penetration from a baseline average was associated with a statistically significant decrease in inappropriate hbA1c and lipid testing, but a statistically insignificant increase in inappropriate TSH testing. The impact of EMR penetration also varied by payment model. CONCLUSIONS: This study demonstrated a positive association between availability of an EMR system and appropriate service utilization. Varying impacts of the EMR system availability by primary care payment model may be reflective of different incentives or attributes inherent in payment models. Policies to encourage physicians to increase their use of laboratory EMR systems could improve the quality and continuity of patient care.

Trends in prevalence of chronic disease and multimorbidity in Ontario, Canada.

BACKGROUND: New case-mix tools from the Canadian Institute for Health Information offer a novel way of exploring the prevalence of chronic disease and multimorbidity using diagnostic data. We took a comprehensive approach to determine whether the prevalence of chronic disease and multimorbidity has been rising in Ontario, Canada. METHODS: In this observational study, we applied case-mix methodology to a population-based cohort. We used 10 years of patient-level data (fiscal years 2008/09 to 2017/18) from multiple care settings to compute the rolling 5-year prevalence of 85 chronic diseases and multimorbidity (i.e., the co-occurrence of 2 or more diagnoses). Diseases were further classified based on type and severity. We report both crude and age- and sex-standardized trends. RESULTS: The number of patients with chronic disease increased by 11.0% over the 10-year study period to 9.8 million in 2017/18, and the number with multimorbidity increased 12.2% to 6.5 million. Overall increases from 2008/09 to 2017/18 in the crude prevalence of chronic conditions and multimorbidity were driven by population aging. After adjustments for age and sex, the prevalence of patients with ≥ 1 chronic conditions decreased from 70.2% to 69.1%, and the prevalence of multimorbidity decreased from 47.1% to 45.6%. This downward trend was concentrated in minor and moderate diseases, whereas the prevalence of many major chronic diseases rose, along with instances of extreme multimorbidity (≥ 8 conditions). Age- and sex-standardized resource intensity weights, which reflect relative expected costs associated with patient diagnostic profiles, increased 4.6%. INTERPRETATION: Evidence of an upward trend in the prevalence of chronic disease was mixed. However, the change in case mix toward more serious conditions, along with increasing patient resource intensity weights overall, may portend a future need for population health management and increased health system spending above that predicted by population aging.

Comparing probability of target attainment against Staphylococcus aureus for ceftaroline fosamil, vancomycin, daptomycin, linezolid, and ceftriaxone in complicated skin and soft tissue infection using pharmacokinetic/pharmacodynamic models.

For recently licensed antibiotics, such as the cephalosporin ceftaroline fosamil, probability of target attainment (PTA) curves, showing the percentage of patients reaching a predefined pharmacokinetic (PK)/pharmacodynamic (PD) target at different bacterial minimum inhibitory concentrations (MICs), have been used to support and justify dose recommendations across patient populations. However, information on PTA for older antibiotics is limited. A retrospective analysis was conducted to construct PTA curves for 4 antibiotics against Staphylococcus aureus in patients with complicated skin and soft tissue infections (cSSTIs). PK models for vancomycin, linezolid, daptomycin, and ceftriaxone were selected from the literature based on large numbers of subjects with covariates representative of patients in Europe and/or the United States. An existing model was available for ceftaroline fosamil. Standard and high-dosage regimens were used to compare the PTA of each antibiotic at MIC values 0.03 to 64 mg/L for a simulated set of patients with cSSTI caused by S. aureus. These were compared to proportions of S. aureus isolates at each MIC from global surveillance data. Ceftaroline achieved PTAs >99.9% for bacteriostatic and bactericidal targets at the MIC90 (1 mg/L), whereas the comparators failed to achieve PTAs >90%, at bacteriostatic or bactericidal targets, even when clinical doses were increased beyond those recommended. PTA analysis can be used to compare different drugs with the same simulated patient dataset, subject to availability of an appropriate PK model and robust exposure targets. This analysis shows that some antibiotics commonly used to treat cSSTIs may fail to reach high PTAs relative to contemporary MIC90 estimates.

A comparison of conventional and minimally invasive multilevel surgery for children with diplegic cerebral palsy.

AIMS: To compare changes in gait kinematics and walking speed 24 months after conventional (C-MLS) and minimally invasive (MI-MLS) multilevel surgery for children with diplegic cerebral palsy (CP). METHODS: A retrospective analysis of 19 children following C-MLS, with mean age at surgery of 12 years five months (seven years ten months to 15 years 11 months), and 36 children following MI-MLS, with mean age at surgery of ten years seven months (seven years one month to 14 years ten months), was performed. The Gait Profile Score (GPS) and walking speed were collected preoperatively and six, 12 and 24 months postoperatively. Type and frequency of procedures as part of MLS, surgical adverse events, and subsequent surgery were recorded. RESULTS: In both groups, GPS improved from the preoperative gait analysis to the six-month assessment with maintenance at 12 and 24 months postoperatively. While reduced at six months in both groups, walking speed returned to preoperative speed by 12 months. The overall pattern of change in GPS and walking speed was similar over time following C-MLS and MI-MLS. There was a median of ten procedures per child as part of both C-MLS (interquartile range (IQR) 8.0 to 11.0) and MI-MLS (IQR 7.8 to 11.0). Surgical adverse events occurred in seven (37%) and 13 (36%) children, with four (21%) and 13 (36%) patients requiring subsequent surgery following C-MLS and MI-MLS, respectively. CONCLUSION: This study indicates similar improvements in gait kinematics and walking speed 24 months after C-MLS and MI-MLS for children with diplegic CP. Cite this article: Bone Joint J 2021;103-B(1):192-197.

Effect of Strict and Soft Policy Interventions on Laboratory Diagnostic Testing in Ontario, Canada: A Bayesian Structural Time Series Analysis.

Applications of behavioral economics targeted at optimizing laboratory utilization among physicians have been implemented in Ontario through different types of nonfinancial interventions. Strict policy interventions restrict Ontario Health Insurance Plan (OHIP) payment for tests to patients with specific conditions or limit ordering to particular physician specialties, while soft policy interventions involve modifications to the laboratory requisition form. This study evaluates the effectiveness of these interventions in terms of changing physician ordering behavior for eight tests that were subject to a strict or soft policy intervention during the study period. We use a Bayesian structural time series model applied to Ontario laboratory claims data for FY2006 through FY2017. Results show a 16-75% reduction in laboratory services with a strict policy intervention and an 8-36% reduction in laboratory services with a soft policy intervention. Although the overall magnitude of change was smaller for soft policy interventions, interventions designed with soft or strict policy mechanisms addressing laboratory utilization management are effective at influencing physicians' test ordering behavior.

Use of the Population Grouping Methodology of the Canadian Institute for Health Information to predict high-cost health system users in Ontario.

BACKGROUND: Prior research has consistently shown that the heaviest users account for a disproportionate share of health care costs. As such, predicting high-cost users may be a precondition for cost containment. We evaluated the ability of a new health risk predictive modelling tool, which was developed by the Canadian Institute for Health Information (CIHI), to identify future high-cost cases. METHODS: We ran the CIHI model using administrative health care data for Ontario (fiscal years 2014/15 and 2015/16) to predict the risk, for each individual in the study population, of being a high-cost user 1 year in the future. We also estimated actual costs for the prediction period. We evaluated model performance for selected percentiles of cost based on the discrimination and calibration of the model. RESULTS: A total of 11 684 427 individuals were included in the analysis. Overall, 10% of this population had annual costs exceeding $3050 per person in fiscal year 2016/17, accounting for 71.6% of total expenditures; 5% had costs above $6374 (58.2% of total expenditures); and 1% exceeded $22 995 (30.5% of total expenditures). Model performance increased with higher cost thresholds. The c-statistic was 0.78 (reasonable), 0.81 (strong) and 0.86 (very strong) at the 10%, 5% and 1% cost thresholds, respectively. INTERPRETATION: The CIHI Population Grouping Methodology was designed to predict the average user of health care services, yet performed adequately for predicting high-cost users. Although we recommend the development of a purpose-designed tool to improve model performance, the existing CIHI Population Grouping Methodology may be used - as is or in concert with additional information - for many applications requiring prediction of future high-cost users.

Pediatric Chronic Postsurgical Pain And Functional Disability: A Prospective Study Of Risk Factors Up To One Year After Major Surgery.

BACKGROUND: Chronic postsurgical pain (CPSP) is a surgical complication associated with increased functional disability, psychological distress, and economic costs. The aims of this paper were to prospectively: (1) examine the incidence of CPSP 6 and 12 months after pediatric major surgery; (2) identify pain intensity and pain unpleasantness trajectories before, and up to 12 months after, surgery; (3) identify pre-operative factors that predict pain trajectory group membership; and (4) identify predictors of 12-month functional disability. METHODS: This study followed 265 children aged 8-17 years at four time points (pre-surgical [T0], in-hospital [T1], 6 [T2] and 12 [T3] months after surgery). Children and parents completed pain and psychological questionnaires. In-hospital physical activity was monitored using actigraphy. RESULTS AND DISCUSSION: The incidence of moderate-to-severe CPSP at 6 and 12 months was 35% (95% CI 29.1% to 41.9%) and 38% (95% CI 32.4% to 45.1%), respectively. Three percent (95% CI 1.17% to 6.23%) and 4% (95% CI 1.45% to 6.55%) of children reported using opioids to manage pain at 6 and 12 months, respectively. Growth mixture modeling revealed a two-class trajectory model with a quadratic slope best fit the data for both pain intensity (Bayesian information criterion [BIC] = 3977.03) and pain unpleasantness (BIC = 3644.45) over the 12 months. Preoperative functional disability and cumulative in-hospital opioid consumption predicted pain intensity trajectories. Preoperative functional disability predicted pain unpleasantness trajectories. Preoperative functional disability (OR: 1.05, 95% CI: 1.01 to 1.09) and pain unpleasantness trajectories (OR: 2.59, 95% CI: 1.05 to 6.37) predicted 12-month moderate-to-severe functional disability. CONCLUSION: Pre-surgical functional disability is the only factor that predicts both 12-month functional disability and the course of pain intensity and pain unpleasantness ratings over the 12-month period.

Using Diagnoses to Estimate Health Care Cost Risk in Canada.

OBJECTIVE: Until recently, the options for summarizing Canadian patient complexity were limited to health risk predictive modeling tools developed outside of Canada. This study aims to validate a new model created by the Canadian Institute for Health Information (CIHI) for Canada's health care environment. RESEARCH DESIGN: This was a cohort study. SUBJECTS: The rolling population eligible for coverage under Ontario's Universal Provincial Health Insurance Program in the fiscal years (FYs) 2006/2007-2016/2017 (12-13 million annually) comprised the subjects. MEASURES: To evaluate model performance, we compared predicted cost risk at the individual level, on the basis of diagnosis history, with estimates of actual patient-level cost using "out-of-the-box" cost weights created by running the CIHI software "as is." We next considered whether performance could be improved by recalibrating the model weights, censoring outliers, or adding prior cost. RESULTS: We were able to closely match model performance reported by CIHI for their 2010-2012 development sample (concurrent R=48.0%; prospective R=8.9%) and show that performance improved over time (concurrent R=51.9%; prospective R=9.7% in 2014-2016). Recalibrating the model did not substantively affect prospective period performance, even with the addition of prior cost and censoring of cost outliers. However, censoring substantively improved concurrent period explanatory power (from R=53.6% to 66.7%). CONCLUSIONS: We validated the CIHI model for 2 periods, FYs 2010/2011-2012/2013 and FYs 2014/2015-2016/2017. Out-of-the-box model performance for Ontario was as good as that reported by CIHI for the development sample based on 3-province data (British Columbia, Alberta, and Ontario). We found that performance was robust to variations in model specification, data sources, and time.

What Systematic Reviews Exist for the Effectiveness of Orthopaedic Interventions.

INTRODUCTION: Orthopaedics procedures are frequent and expensive, but highly cost effective in improving the quality of life. The purpose of this study was to determine the number and topics of systematic overviews on the effectiveness of orthopaedic interventions. METHODS: We performed a review of PubMed, Ovid Embase, Scopus, OrthoEvidence, and the Cochrane Library for dates of publication from January 1, 2006, to February 3, 2017, to identify systematic overviews of randomized clinical trials for the effectiveness of therapeutic interventions involving orthopaedic surgeons. Abstracts were excluded based on the following sequentially applied criteria: (1) the systematic review did not include an intervention for an orthopaedic condition; the intervention was not therapeutic; the intervention was not likely to be applied or influenced by an orthopaedic surgeon; (2) the study was not a systematic review or the study was a single randomized controlled trial, and/or it included nonhuman studies; (3) the systematic review included nonrandomized studies; and (4) the systematic review did not state moderate or strong evidence in support of the study conclusion(s). RESULTS: Of the 6,864 abstracts found in the searches, 6,145 were excluded yielding 719 systematic overviews. Contrary to conventional wisdom, this study identified 719 reviews of randomized controlled trials of therapeutic orthopaedic interventions. The interventions were classified as surgical in 383 (55%), medication in 245 (34%), and rehabilitation in 42 (6%), and other nonsurgical interventions in 39 (5%). DISCUSSION: This study identified many systematic overviews of orthopaedic interventions. The findings of this study could both influence clinical practice and, given the frequency of orthopaedic procedures, have a major public health impact.

A Retrospective Analysis of Probability of Target Attainment in Community-Acquired Pneumonia: Ceftaroline Fosamil Versus Comparators.

INTRODUCTION: This retrospective analysis compares the probability of target attainment (PTA) for ceftriaxone, levofloxacin and ceftaroline fosamil against Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in a representative patient population with moderate-to-severe community-acquired pneumonia (CAP). METHODS: Published pharmacokinetic (PK) models for levofloxacin and ceftriaxone, and an existing model for ceftaroline, were used with standard dosage regimens for simulating individual PK data with covariates representative of patients with CAP (5000 patients/drug regimen). PTA for clinically relevant pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated from steady state PK profiles for a range of minimum inhibitory concentrations (MICs). Cumulative fractions of response (CFRs) were also calculated using MIC distributions from 2012 to 2017 global surveillance data. RESULTS: Ceftaroline fosamil (600 mg q12 h) achieved > 90% PTA at all exposure targets for each pathogen at European Committee on Antimicrobial Susceptibility Testing (EUCAST)/Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints, and CFRs were > 99%. Ceftriaxone, but not levofloxacin, achieved 100% PTA and > 90% CFR against S. pneumoniae. Both levofloxacin and ceftriaxone achieved high PTA and CFR against H. influenzae. Levofloxacin achieved PTAs < 90% at EUCAST/CLSI breakpoints and ceftriaxone achieved PTAs < 90% at MICs up to 2 mg/L against S. aureus; both agents produced generally low CFRs against S. aureus (except levofloxacin against methicillin-sensitive S. aureus), reflecting the lack of activity of these agents against methicillin-resistant S. aureus. CONCLUSION: Ceftaroline fosamil demonstrated higher overall PTA rates than levofloxacin and ceftriaxone, in particular against S. aureus. These results provide insight regarding the potential comparative efficacy of the described antibiotics for moderate-to-severe CAP. FUNDING: Pfizer.