Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy.

INTRODUCTION: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3­DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population. METHODS: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart). RESULTS: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%. CONCLUSION: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

Periodontal treatment and subsequent clinical outcomes and medical care costs: A retrospective cohort study.

INTRODUCTION: Periodontitis is a common oral disease associated with coronary artery disease (CAD), cerebrovascular disease (CBVD) and type 2 diabetes (T2D). We studied if periodontitis treatment improves clinical outcomes and reduces medical care costs in patients with CAD, CBVD or T2D. METHODS: We used clinic records and claims data from a health care system to identify patients with periodontitis and CAD, CBVD or T2D, and to assess periodontal treatments, hospitalizations, medical costs (total, inpatient, outpatient, pharmacy), glycated hemoglobin, cardiovascular events, and death following concurrent disease diagnoses. We compared clinical outcomes according to receipt of periodontal treatment and/or maintenance care in the follow-up period, and care costs according to treatment status within one year following concurrent disease diagnoses, while adjusting for covariates. The data were analyzed in 2019-21. RESULTS: We identified 9,503 individuals, 4,057 of whom were in the CAD cohort; 3,247 in the CBVD cohort; and 4,879 in the T2D cohort. Patients who were selected and elected to receive treatment and maintenance care were less likely to be hospitalized than untreated individuals (CAD: OR = 0.71 (95% CI: 0.55, 0.92); CBVD: OR = 0.73 (0.56, 0.94); T2D: OR = 0.80 (0.64, 0.99)). Selection to treatment and/or maintenance care was not significantly associated with cardiovascular events, mortality, or glycated hemoglobin change. Total care costs did not differ significantly between treated and untreated groups over 4 years. Treated patients experienced lower inpatient costs but higher pharmacy costs. CONCLUSIONS: Patients with periodontitis and CAD, CBVD or T2D who were selected and elected to undergo periodontal treatment or maintenance care had lower rates of hospitalizations, but did not differ significantly from untreated individuals in terms of clinical outcomes or total medical care costs.

Impact of the COVID-19 Pandemic on Type 2 Diabetes Care Delivery.

The coronavirus disease 2019 (COVID-19) pandemic instigated major changes in care delivery, but our understanding of how the rapid transition from in-person to telehealth encounters affected the care of patients with chronic conditions such as type 2 diabetes remains incomplete. This study examined changes in primary care encounters, A1C testing rates, and the likelihood of meeting A1C guidelines before and during the first 9 months of the COVID-19 pandemic in a large health care system. It found significant decreases in utilization and testing rates and the likelihood of meeting A1C guidelines, primarily driven by missing A1C tests. Patients who had all telehealth encounters or no encounters, who identified as racial or ethnic minorities, or had Medicaid or no insurance were significantly more likely to miss A1C tests.

Comparing Pharmacist-Led Telehealth Care and Clinic-Based Care for Uncontrolled High Blood Pressure: The Hyperlink 3 Pragmatic Cluster-Randomized Trial.

BACKGROUND: A team approach is one of the most effective ways to lower blood pressure (BP) in uncontrolled hypertension, but different models for organizing team-based care have not been compared directly. METHODS: A pragmatic, cluster-randomized trial compared 2 interventions in adult patients with moderately severe hypertension (BP≥150/95 mm Hg): (1) clinic-based care using best practices and face-to-face visits with physicians and medical assistants; and (2) telehealth care using best practices and adding home BP telemonitoring with home-based care coordinated by a clinical pharmacist or nurse practitioner. The primary outcome was change in systolic BP over 12 months. Secondary outcomes were change in patient-reported outcomes over 6 months. RESULTS: Participants (N=3071 in 21 primary care clinics) were on average 60 years old, 47% male, and 19% Black. Protocol-specified follow-up within 6 weeks was 32% in clinic-based care and 27% in telehealth care. BP decreased significantly during 12 months of follow-up in both groups, from 157/92 to 139/82 mm Hg in clinic-based care patients (adjusted mean difference -18/-10 mm Hg) and 157/91 to 139/81 mm Hg in telehealth care patients (adjusted mean difference -19/-10 mm Hg), with no significant difference in systolic BP change between groups (-0.8 mm Hg [95% CI, -2.84 to 1.32]). Telehealth care patients were significantly more likely than clinic-based care patients to report frequent home BP measurement, rate their BP care highly, and report that BP care visits were convenient. CONCLUSIONS: Telehealth care that includes extended team care is an effective and safe alternative to clinic-based care for improving patient-centered care for hypertension. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02996565.

Bolstering the Business Case for Adoption of Shared Decision-Making Systems in Primary Care: Randomized Controlled Trial.

BACKGROUND: Limited budgets may often constrain the ability of health care delivery systems to adopt shared decision-making (SDM) systems designed to improve clinical encounters with patients and quality of care. OBJECTIVE: This study aimed to assess the impact of an SDM system shown to improve diabetes and cardiovascular patient outcomes on factors affecting revenue generation in primary care clinics. METHODS: As part of a large multisite clinic randomized controlled trial (RCT), we explored the differences in 1 care system between clinics randomized to use an SDM intervention (n=8) versus control clinics (n=9) regarding the (1) likelihood of diagnostic coding for cardiometabolic conditions using the 10th Revision of the International Classification of Diseases (ICD-10) and (2) current procedural terminology (CPT) billing codes. RESULTS: At all 24,138 encounters with care gaps targeted by the SDM system, the proportion assigned high-complexity CPT codes for level of service 5 was significantly higher at the intervention clinics (6.1%) compared to that in the control clinics (2.9%), with P<.001 and adjusted odds ratio (OR) 1.64 (95% CI 1.02-2.61). This was consistently observed across the following specific care gaps: diabetes with glycated hemoglobin A1c (HbA1c)>8% (n=8463), 7.2% vs 3.4%, P<.001, and adjusted OR 1.93 (95% CI 1.01-3.67); blood pressure above goal (n=8515), 6.5% vs 3.7%, P<.001, and adjusted OR 1.42 (95% CI 0.72-2.79); suboptimal statin management (n=17,765), 5.8% vs 3%, P<.001, and adjusted OR 1.41 (95% CI 0.76-2.61); tobacco dependency (n=7449), 7.5% vs. 3.4%, P<.001, and adjusted OR 2.14 (95% CI 1.31-3.51); BMI >30 kg/m2 (n=19,838), 6.2% vs 2.9%, P<.001, and adjusted OR 1.45 (95% CI 0.75-2.8). Compared to control clinics, intervention clinics assigned ICD-10 diagnosis codes more often for observed cardiometabolic conditions with care gaps, although the difference did not reach statistical significance. CONCLUSIONS: In this randomized study, use of a clinically effective SDM system at encounters with care gaps significantly increased the proportion of encounters assigned high-complexity (level 5) CPT codes, and it was associated with a nonsignificant increase in assigning ICD-10 codes for observed cardiometabolic conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02451670; https://clinicaltrials.gov/ct2/show/NCT02451670.

Comparison of explanatory and pragmatic design choices in a cluster-randomized hypertension trial: effects on enrollment, participant characteristics, and adherence.

BACKGROUND: Explanatory trials are designed to assess intervention efficacy under ideal conditions, while pragmatic trials are designed to assess whether research-proven interventions are effective in "real-world" settings without substantial research support. METHODS: We compared two trials (Hyperlink 1 and 3) that tested a pharmacist-led telehealth intervention in adults with uncontrolled hypertension. We applied PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) scores to describe differences in the way these studies were designed and enrolled study-eligible participants, and the effect of these differences on participant characteristics and adherence to study interventions. RESULTS: PRECIS-2 scores demonstrated that Hyperlink 1 was more explanatory and Hyperlink 3 more pragmatic. Recruitment for Hyperlink 1 was conducted by study staff, and 2.9% of potentially eligible patients enrolled. Enrollees were older, and more likely to be male and White than non-enrollees. Study staff scheduled the initial pharmacist visit and adherence to attending this visit was 98%. Conversely for Hyperlink 3, recruitment was conducted by clinic staff at routine encounters and 81% of eligible patients enrolled. Enrollees were younger, and less likely to be male and White than non-enrollees. Study staff did not assist with scheduling the initial pharmacist visit and adherence to attending this visit was only 27%. Compared to Hyperlink 1, patients in Hyperlink 3 were more likely to be female, and Asian or Black, had lower socioeconomic indicators, and were more likely to have comorbidities. Owing to a lower BP for eligibility in Hyperlink 1 (>140/90 mm Hg) than in Hyperlink 3 (>150/95 mm Hg), mean baseline BP was 148/85 mm Hg in Hyperlink 1 and 158/92 mm Hg in Hyperlink 3. CONCLUSION: The pragmatic design features of Hyperlink 3 substantially increased enrollment of study-eligible patients and of those traditionally under-represented in clinical trials (women, minorities, and patients with less education and lower income), and demonstrated that identification and enrollment of a high proportion of study-eligible subjects could be done by usual primary care clinic staff. However, the trade-off was much lower adherence to the telehealth intervention than in Hyperlink 1, which is likely to reflect uptake under real-word conditions and substantially dilute intervention effect on BP. TRIAL REGISTRATION: The Hyperlink 1 study (NCT00781365) and the Hyperlink 3 study (NCT02996565) are registered at ClinicalTrials.gov.

Association of an Automated Blood Pressure Measurement Quality Improvement Program With Terminal Digit Preference and Recorded Mean Blood Pressure in 11 Clinics.

Importance: Terminal digit preference has been shown to be associated with inaccurate blood pressure (BP) recording. Objective: To evaluate whether converting from manual BP measurement with aneroid sphygmomanometers to automated BP measurement was associated with terminal digit preference, mean levels of recorded BP, and the rate at which hypertension was diagnosed. Design, Setting, and Participants: This quality improvement study was conducted from May 9, 2021, to March 24, 2022, using interrupted time series analysis of medical record data from 11 primary care clinics in a single health care system from April 2008 to April 2015. The study population was patients aged 18 to 75 years who had their BP measured and recorded at least once during the study period. Exposures: Manual BP measurement before April 2012 vs automated BP measurement with the Omron HEM-907XL monitor from May 2012 to April 2015. Main Outcomes and Measures: The main outcome was the distribution of terminal digits and mean systolic BP (SBP) values obtained during 4 years of manual measurement vs 3 years of automated measurement, assessed using a generalized linear mixed regression model with a random intercept for clinic and adjusted for seasonal fluctuations and patient demographic and clinical characteristics. Results: The study included 1 541 227 BP measurements from 225 504 unique patients during the entire study period, with 849 978 BP measurements from 165 137 patients (mean [SD] age, 47.1 [15.2] years; 58.2% female) during the manual measurement period and 691 249 measurements from 149 080 patients (mean [SD] age, 48.4 [15.3] years; 56.3% female) during the automated measurement period. With manual measurement, 32.8% of SBP terminal digits were 0 (20% was the expected value because nursing staff was instructed to record BP to the nearest even digit). This proportion decreased to 12.4% during the automated measurement period (expected value, 10%) when both even and odd digits were to be recorded. After automated measurement was implemented, the mean SBP estimated with statistical modeling increased by 5.09 mm Hg (95% CI, 4.98-5.19 mm Hg). Fewer BP values recorded during the automated than the manual measurement period were below 140/90 mm Hg (69.9% vs 84.3%; difference, -14.5%; 95% CI, -14.6% to -14.3%) and below 130/80 mm Hg (42.1% vs 60.0%; difference, -17.9%; 95% CI, -18.0% to -17.7%). The proportion of patients with a diagnosis of hypertension was 4.3 percentage points higher (23.4% vs 19.1%) during the automated measurement period. Conclusions and Relevance: In this quality improvement study, automated BP measurement was associated with decreased terminal digit preference and significantly higher mean BP levels. The method of BP measurement was also associated with the rate at which hypertension was diagnosed. These findings may have implications for pay-for-performance programs, which may create an incentive to record BP levels that meet a particular goal and a disincentive to adopt automated measurement of BP.

Association of Cardiovascular Outcomes and Mortality With Sustained Long-Acting Insulin Only vs Long-Acting Plus Short-Acting Insulin Treatment.

Importance: Cardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes. Objective: To compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin. Design, Setting, and Participants: This retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019. Exposures: Long-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level. Main Outcomes and Measures: Mortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure. Results: Among 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality. Conclusions and Relevance: Findings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.

Radiographic correlation of clinical shoulder deformity and patient perception following scapula fracture.

BACKGROUND: Interest in operative management of scapular fractures is increasing based upon defined radiographic displacement criteria and growing awareness that certain extra-articular fractures will not do well and result in dysfunction and deformity (slumped shoulder). We intend to quantify clinical deformity, analyze correlations of these novel measures with defined radiographic measures of fracture displacement and with the patients' reported perception of their deformity. METHODS: Prospectively enrolled patients underwent standardized questioning regarding their perception of the deformity. Radiographs were utilized to measure glenopolar angle medial/lateral displacement, and angulation of the displaced scapula fracture. Novel measurements of clinical deformity (shoulder area, shoulder angle and shoulder height difference) were calculated. All measurements were repeated post-operatively for patients undergoing operative treatment. RESULTS: Fifty-one patients (39 operative) were examined within 30 days of injury. Follow-up (≥2 months post-op) was obtained for 31/39 (79%). Medial-lateral displacement significantly correlated with all measures of clinical deformity and with patient reported shoulder appearance bothersome score. Angulation significantly correlated with patient perception and two clinical measures (shoulder area and shoulder angle difference). All post-operative radiographic measures, clinical measures of deformity, and patient reported scores statistically improved from baseline measures. DISCUSSION: Patients with scapula fracture do perceive deformity, and there is a significant correlation between the patients' perception, radiographic and clinical measurements of deformity after scapula fracture. All measures statistically improved in patients with operative treatment compared to baseline measurements. This study reinforces the importance of the clinicians' clinical examination and observation of shoulder deformity in the scapula fracture patient. LEVEL OF EVIDENCE: IV.

Design of a pragmatic cluster-randomized trial comparing telehealth care and best practice clinic-based care for uncontrolled high blood pressure.

BACKGROUND: Uncontrolled hypertension is the largest single contributor to all-cause and cardiovascular mortality in the U.S. POPULATION: Nurse- and pharmacist-led team-based care and telehealth care interventions have been shown to result in large and lasting improvements in blood pressure (BP); however, it is unclear how successfully these can be implemented at scale in real-world settings. It is also uncertain how telehealth interventions impact patient experience compared to traditional clinic-based care. AIMS/OBJECTIVES: To compare the effects of two evidence-based blood pressure care strategies in the primary care setting: (1) best-practice clinic-based care and (2) telehealth care with home BP telemonitoring and management by a clinical pharmacist. To evaluate implementation using mixed-methods supported by the RE-AIM framework and Consolidated Framework for Implementation Research. METHODS: The design is a cluster-randomized comparative effectiveness pragmatic trial in 21 primary care clinics (9 clinic-based care, 12 telehealth care). Adult patients (age 18-85) with hypertension are enrolled via automated electronic health record (EHR) tools during primary care encounters if BP is elevated to ≥150/95 mmHg at two consecutive visits. The primary outcome is change in systolic BP over 12 months as extracted from the EHR. Secondary outcomes are change in key patient-reported outcomes over 6 months as measured by surveys. Qualitative data are collected at various time points to investigate implementation barriers and help explain intervention effects. CONCLUSION: This pragmatic trial aims to inform health systems about the benefits, strengths, and limitations of implementing home BP telemonitoring with pharmacist management for uncontrolled hypertension in real-world primary care settings.

Emergency medicine physicians' ability to predict hospital admission at the time of triage.

BACKGROUND: We seek to determine if experienced emergency medicine physicians can accurately predict the likelihood of admission for patients at the time of triage. Such predictions, if proven to be accurate, could decrease the time spent in the ED for patients who will ultimately be admitted by hastening downstream workflow. METHODS: This is a prospective cohort study of experienced physicians at a large urban hospital. Physicians were asked to predict the likelihood of admission for patients based only on information available in the EMR at the time of triage. Physicians also predicted the service to which the patients would be admitted. Physicians provided a confidence level of their prediction. Measures of predictive accuracy were calculated, including sensitivity, specificity, and area under the receiver operating characteristic curve. RESULTS: 35 physicians evaluated 398 patient charts and made predictions. Sensitivity of determining admission for the entire cohort was 51.8%. The specificity was 89.1%. For those predictions made with a confidence level of >90%, sensitivity was 61.5% and specificity was 95.7%. Among physicians correctly predicting admission, the admitting service was predicted accurately 88.6% of the time. CONCLUSION: Physicians performed poorly at predicting which patients would be admitted at the time of triage, even when they were confident in their predictions. Conversely, physicians accurately predicted who would be discharged. Physicians predicted with reasonable accuracy the service to which patients were ultimately admitted. More research and operational assessment needs to be performed to determine if these predictions can help improve ED efficiency.

Frequent 911 Fall Calls in Older Adults: Opportunity for Injury Prevention Strategies.

OBJECTIVES: To evaluate the utility of monitoring emergency medical services (EMS) call patterns to identify older adults who may benefit from targeted fall prevention and medical monitoring strategies. DESIGN: Retrospective chart review of EMS fall-related care. The HealthEMS database for the community surveyed was queried from January 1, 2007, through December 31, 2016. Fall-related calls for individuals aged 60 and older were identified and used to determine which individuals had subsequent fall calls and needed transport to the hospital over the study time period. SETTING: Medium-sized suburban community. PARTICIPANTS: Community-dwelling adults aged 60 and older with fall-related calls. MEASUREMENTS: Descriptive EMS cell data. RESULTS: Over the 10-year period, 37,324 EMS call data were recorded, with 11% (N=4,084) identified as fall-related calls that occurred for individuals aged 60 and older. Twenty-nine percent (n=685) of individuals who called for a fall called at least one more time within the study period. Time between calls substantially decreased the more frequently an individual called (p<.001). Fifteen percent (n=107) of repeat callers called 5 or more times for falls, and these individuals were transported to the hospital only 21% of the time (vs 75% of first-time callers, p <.001). CONCLUSION: Certain older individuals are at risk of having multiple fall-related calls to EMS over short periods of time, sometimes within hours of previous calls. In our current healthcare system, no significant intervention or follow-up is offered or available by emergency first response teams to prevent subsequent falls. This study demonstrates the need for a paradigm change in our healthcare system that helps reduce resource utilization for the first responder community for fall-related calls in older adults and re-directs those resources to implement nationwide fall-prevention strategies to decrease fall related disability and death.

Predictors of Mortality in Elder Patients With Proximal Humeral Fracture.

BACKGROUND: Known possible consequences of proximal humerus fractures include impaired shoulder function, decreased independence, and increased risk for mortality. The purpose of this report is to describe the survival and independence of elderly patients with fractures of the proximal humerus, treated in our institution, relative to patient characteristics and treatment method. METHODS: Retrospective cohort study from 2006 to 2012. SETTING: Community-based hospital with level 1 designation. PATIENTS/PARTICIPANTS: Three hundred nineteen patients ≥60 years who presented to the emergency department with an isolated fracture of the proximal humerus were either admitted to the inpatient ward for the organization and provision of immediate definitive care or discharged with the expectation of coordination of their care as an outpatient. Treatment was nonoperative or operative. OUTCOME MEASURES: One- and 2-year mortality. RESULTS: Significant predictors of mortality at 1 year included Charlson Comorbidity Index (CCI; continuous, hazard ratio [HR] = 1.40; 95% confidence interval [CI]: 1.06-1.86), body mass index (BMI; <25 vs ≥25; HR = 3.43; 95% CI: 1.45-8.14), and American Society of Anesthesiologists (ASA) disease severity score (3-4 vs 1-2; HR = 4.48; 95% CI: 1.21-16.55). In addition to CCI and BMI, reliance on a cane/walker/wheelchair at the time of fracture predicted mortality at 2 years (vs unassisted ambulation; HR = 3.13; 95% CI: 1.59-5.88). Although the Neer classification of fracture severity significantly correlated with inpatient admission (P < .001), it was not significantly associated with mortality or with loss of living or ambulatory independence. Among admitted patients, 64% were discharged to a facility with a higher level of care than their prefracture living facility. Twenty percent of study patients experienced a loss in ambulatory status by at least 1 level at 1 year postfracture. CONCLUSION: In a cohort of elderly patients with fractures of the proximal humerus, patient characteristics including comorbidities, ASA classification, and lower BMI were associated with increased mortality. Specifically, those admitted at the time of fracture and treated nonoperatively had the highest mortality rate and, likely, represent the frailest cohort. Those initially treated as outpatients and later treated operatively had the lowest mortality and, likely, represent the healthiest cohort. These data are inherently biased by prefracture comorbidities but help stratify our patients' mortality risk at the time of injury.

Displacement of diaphyseal clavicle fractures related to patient position and progressive displacement in the peri-injury period.

BACKGROUND: The purposes of this study were (1) to determine how supine versus upright patient position affects the measurement of diaphyseal clavicle fracture displacement, (2) to describe the incidence of progressive displacement in the peri-injury period, and (3) to investigate variables associated with the progressive displacement. METHODS: Between 2013 and 2015, patients aged 14 years or older presenting with a diaphyseal clavicle fracture within 7 days of injury were included (N = 50). A well-defined radiographic protocol was established. Nine patients underwent surgery after the second follow-up, and the remaining 41 patients, who did not undergo surgery, received the full complement of measures at the first, second, and third follow-up time points. The second follow-up (8-21 days after injury) and third follow-up (22-60 days after injury) had the same defined radiographic protocol as the first visit. The amount of displacement and angulation was measured in both the supine and upright positions on the initial injury radiographs and subsequent follow-up radiographs. RESULTS: Vertical translation was 2.4 mm (95% confidence interval, 1.8-3.0 mm) greater and angulation was 3.9° (95% confidence interval, 3.3°-4.6°) greater in the upright position. Progressive displacement occurred in 16 patients (32%). Older age (P = .015) and ipsilateral shoulder girdle or chest wall injury (P = .007) were significantly associated with progressive displacement. CONCLUSIONS: Upright radiographs evaluate maximal displacement in diaphyseal clavicle fractures. Close follow-up of nonoperatively treated clavicle fractures is warranted. Progressive displacement was more likely in older patients and/or those who had ipsilateral shoulder girdle or chest wall injury.

Placement of a cervical collar increases the optic nerve sheath diameter in healthy adults.

INTRODUCTION: Blunt head trauma is a common cause of increased intracranial pressure (ICP). Ultrasound measurement of the optic nerve sheath diameter (OSND) is an accurate and non-invasive way to detect increased ICP. Blunt trauma patients are often immobilized in a rigid cervical spine collar. Our objective was to describe the changes in ONSD following the placement of a c-collar and determine if any changes were time-dependent. METHODS: We performed a prospective cohort study measuring the ONSD of healthy volunteers before and after placement of a c-collar. Two physicians obtained the measurements. Each eye was scanned twice using a standardized technique. This was done before c-collar placement, 5min after placement and 20min after placement. A mean of both eyes was calculated and analyzed using descriptive statistics. An intraclass correlation coefficient (ICC) was used to assess inter-rater reliability. RESULTS: Twenty study participants with a mean age of 37.1years old were enrolled. The mean baseline ONSD was 3.77mm (95% CI 3.48-4.07). The mean ONSD 5 min after the c-collar was placed was 4.47 (95% CI 4.17-4.78). The mean ONSD at 20min after c-collar placement was 4.53 (95% CI 4.13-4.92). These changes were statistically significant (p=0.003 and <0.001). Reliability was relatively strong overall (ICC=0.74; 95% CI: 0.65, 0.81). CONCLUSION: The placement of a cervical collar increased the ONSD at 5min and this change remained increased at 20min. Future study should assess whether similar results are found in patients with blunt head trauma.

Comparison and predictors of treatment adherence and remission among patients with schizophrenia treated with paliperidone palmitate or atypical oral antipsychotics in community behavioral health organizations.

BACKGROUND: Nonadherence to antipsychotic treatment increases the likelihood of relapse and progressive symptomatology in patients with schizophrenia. Atypical long-acting injectables, including paliperidone palmitate (PP), may increase adherence and improve symptoms. This study compared and assessed predictors of treatment patterns and symptom remission among schizophrenia patients treated with PP versus atypical oral antipsychotic therapy (OAT) in community behavioral health organizations (CBHOs). METHODS: This retrospective cohort analysis evaluated 763 patients with schizophrenia and new (PP-N; N = 174) or continuing (PP-C; N = 308) users of PP, or new users of OAT (N = 281) at enrollment in the REACH-OUT study (2010-2013). Treatment outcomes assessed at 1 year were discontinuation, and adherence, measured by proportion of days covered (PDC) or medication possession ratio (MPR). Remission status was assessed using the Structured Clinical Interview for Symptoms of Remission (SCI-SR). A machine learning platform, Reverse Engineering and Forward Simulation (REFS™), was used to identify predictors of study outcomes. Multivariate Cox and generalized linear regressions estimated the adjusted hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals. RESULTS: Among PP-N users, 27% discontinued their initial treatment regimen versus 51% (p < 0.001) of OAT users. PP-N (vs OAT; HR = 0.49 [0.31-0.76]) users and males (HR = 0.65 [0.46-0.92]) had significantly lower rates of discontinuation. Relative to OAT, PP-N had a 36% [31%-42%] higher MPR and a 10-fold increased achievement of PDC ≥80% (OR = 10.46 [5.72-19.76]). PP users were significantly more likely to achieve remission in follow-up (PP-N vs OAT: OR = 2.65 [1.39-5.05]; PP-C vs OAT: OR = 1.83 [1.03-3.25]). CONCLUSIONS: Relative to OAT, PP was associated with improved adherence, less frequent treatment discontinuation, and improved symptom remission in this CBHO study population.

Reverse Engineering and Evaluation of Prediction Models for Progression to Type 2 Diabetes: An Application of Machine Learning Using Electronic Health Records.

BACKGROUND: Application of novel machine learning approaches to electronic health record (EHR) data could provide valuable insights into disease processes. We utilized this approach to build predictive models for progression to prediabetes and type 2 diabetes (T2D). METHODS: Using a novel analytical platform (Reverse Engineering and Forward Simulation [REFS]), we built prediction model ensembles for progression to prediabetes or T2D from an aggregated EHR data sample. REFS relies on a Bayesian scoring algorithm to explore a wide model space, and outputs a distribution of risk estimates from an ensemble of prediction models. We retrospectively followed 24 331 adults for transitions to prediabetes or T2D, 2007-2012. Accuracy of prediction models was assessed using an area under the curve (AUC) statistic, and validated in an independent data set. RESULTS: Our primary ensemble of models accurately predicted progression to T2D (AUC = 0.76), and was validated out of sample (AUC = 0.78). Models of progression to T2D consisted primarily of established risk factors (blood glucose, blood pressure, triglycerides, hypertension, lipid disorders, socioeconomic factors), whereas models of progression to prediabetes included novel factors (high-density lipoprotein, alanine aminotransferase, C-reactive protein, body temperature; AUC = 0.70). CONCLUSIONS: We constructed accurate prediction models from EHR data using a hypothesis-free machine learning approach. Identification of established risk factors for T2D serves as proof of concept for this analytical approach, while novel factors selected by REFS represent emerging areas of T2D research. This methodology has potentially valuable downstream applications to personalized medicine and clinical research.

CD4 recovery on antiretroviral therapy is associated with decreased progression to liver disease among hepatitis C virus-infected injecting drug users.

Background. Human immunodeficiency virus (HIV) coinfection accelerates liver disease progression in individuals with chronic hepatitis C. We evaluated the associations of CD4, HIV RNA, and antiretroviral therapy (ART)-induced CD4 recovery with liver diagnoses in a prospective cohort of injecting drug users (IDUs). Methods. We evaluated 383 coinfected IDUs in the Boston area, prospectively observed for a median of 1.8 years. Liver disease progression included the first occurrence of hepatocellular carcinoma, variceal bleeding, ascites, encephalopathy, or death due to hepatic failure. Multivariable-adjusted extended Cox models were specified to estimate hazard ratios (HRs) for comparisons of CD4, change in CD4 (from nadir), and HIV RNA with respect to liver disease progression events. Results. Twenty-four persons experienced a liver disease progression event over 1155 person-years (2.1 per 100 person-years), including 20 deaths attributed to end-stage liver disease (1.7 per 100 person-years). CD4 at baseline and over follow-up strongly predicted liver disease progression (baseline CD4 <200 vs ≥200: HR = 5.23, 95% confidence interval [CI], 2.30-11.92; time-updated CD4 <200 vs ≥200: HR = 11.79, 95% CI, 4.47-31.07). Nadir CD4 was also a strong indicator (<100 vs ≥100: HR = 3.52, 95% CI, 1.54-8.06). A lack of CD4 recovery (failure to increase 100 cells over nadir) among ART initiators was associated with increased risk (HR = 7.69; 95% CI, 2.60-22.69). Human immunodeficiency virus RNA was not significantly associated with liver disease progression. Conclusions. Impaired immune function was highly predictive of liver disease progression in this cohort of IDUs, and a lack of CD4 recovery on ART was associated with increased risk of progression to HCV-associated liver disease.

Antiretroviral therapy reduces the rate of hepatic decompensation among HIV- and hepatitis C virus-coinfected veterans.

BACKGROUND: Human immunodeficiency virus (HIV) coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure. METHODS: We evaluated 10 090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying ART regimen of ≥3 drugs from ≥2 classes. Hepatic decompensation was defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HRs) of hepatic decompensation, comparing initiation of ART to noninitiation. RESULTS: We observed 645 hepatic decompensation events in 46 444 person-years of follow-up (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to noninitiators (HR = 0.72; 95% confidence interval [CI], .54-.94). When we removed individuals with HIV RNA ≤400 copies/mL at baseline from the analysis (assuming that they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR = 0.59; 95% CI, .43-.82). CONCLUSIONS: Initiation of ART significantly reduced the rate of hepatic decompensation by 28%-41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease.

Central Nervous System Vasculopathy in HIV-Infected Children Enrolled in the Pediatric AIDS Clinical Trials Group 219/219C Study.

BACKGROUND: Central nervous system (CNS) vasculopathy has been reported in human immunodeficiency virus-infected (HIV+) adults and children. In children, it often presents with HIV encephalopathy, stroke, or intracerebral aneurysms. The etiology, incidence, and risk factors of HIV-associated CNS vasculopathy in children are unknown. METHODS: We identified HIV+ children with a diagnosis of vasculopathy or other cerebrovascular events among children enrolled between 1993 and 2004 in 2 prospective, multicenter cohort studies. Demographic and laboratory data, history of antiretroviral use, and signs, symptoms, and diagnostic studies pertaining to the CNS event were reviewed. RESULTS: Among the 3338 HIV+ children, 51 had diagnoses that suggested CNS vasculopathy. Of these, 12 (24%) were included in this analysis, after excluding those with alternative diagnoses and those from closed sites. Among these 12, 4 (33%) were female, 4 (33%) were white, and 10 (83%) had perinatal HIV. Their average age at the event was 10.8 years with a median CD4 count of 22 cells/mm(3) and median HIV-1 viral load of 94 304 copies/mL. Fifty-eight percent of subjects had a history of opportunistic infections before the CNS event. Fifty percent had cerebral aneurysms on imaging. The overall incidence among HIV+ subjects was 3.4 cases per 10 000 person-years (95% confidence interval, 1.8-6.0). CONCLUSIONS: CNS vasculopathy in HIV+ children is uncommon but more common than in the general pediatric population. Cerebral aneurysms are the most common manifestation. Although the pathogenesis remains unclear, older children and those with low CD4 counts and high HIV viral loads are at the highest risk.