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BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.

BackgroundThe COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans.MethodsAmerican Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon.ResultsTwelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66).ConclusionAlthough some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

PurposeActive surveillance (AS) for grade group (GG) 2 patients is not yet well defined. We sought to compare clinical outcomes of men with GG1 and GG2 prostate cancer undergoing AS in a large prospective North American cohort.Materials and methodsParticipants were prospectively enrolled in an AS study with protocol-directed followup at 10 centers in the U.S. and Canada. We evaluated time from diagnosis to biopsy grade reclassification and time to treatment. In men treated after initial surveillance, adverse pathology and recurrence were also analyzed.ResultsAt diagnosis, 154 (9%) had GG2 and 1,574 (91%) had GG1. Five-year reclassification rates were similar between GG2 and GG1 (30% vs 37%, p=0.11). However, more patients with GG2 were treated at 5 years (58% vs 34%, p

BackgroundPatients with lower extremity wounds from diabetes mellitus or peripheral artery disease (PAD) have a risk of amputation as high as 25%. In patients with arterial disease, revascularization decreases the risk of amputation. We aimed to determine if the early assessment of arterial perfusion correlates with the risk of amputation.MethodsWe retrospectively reviewed patients referred to the vascular clinic over 18 months with Rutherford Grade 5 and 6 chronic limb-threatening ischemia to determine if patients had a pulse exam done at the time the wound was identified and when ankle brachial index (ABI) testing to evaluate perfusion was performed. Kaplan Meier analysis was used to determine if the timing of ABI testing affected the time to revascularization, wound healing, and risk of amputation.ResultsNinety-three patients with lower extremity wounds were identified. Of these, 59 patients (63%) did not have a pulse exam performed by their primary care provider when the wound was identified. Patients were classified by when they underwent ankle brachial index testing to assess arterial perfusion. Twenty-four had early ABI (

Background and purposeAdvancements in carotid revascularization have produced promising outcomes in patients with symptomatic carotid artery stenosis. However, the optimal timing of revascularization procedures after symptomatic presentation remains unclear. The purpose of this study is to compare in-hospital outcomes of transcarotid artery revascularization (TCAR), transfemoral carotid stenting (TFCAS), or carotid endarterectomy (CEA) performed within different time intervals after most recent symptoms.MethodsThis is a retrospective cohort study of United States patients in the vascular quality initiative. All carotid revascularizations performed for symptomatic carotid artery stenosis between September 2016 and November 2019 were included. Procedures were categorized as urgent (0-2 days after most recent symptom), early (3-14 days), or late (15-180 days). The primary outcome of interest was in-hospital stroke and death. Secondary outcomes include in-hospital stroke, death, and transient ischemic attacks. Multivariable logistic regression was used to compare outcomes.ResultsA total of 18 643 revascularizations were included: 2006 (10.8%) urgent, 7423 (39.8%) early, and 9214 (49.42%) late. Patients with TFCAS had the highest rates of stroke/death at all timing cohorts (urgent: 4.0% CEA, 6.9% TFCAS, 6.5% TCAR, P=0.018; early: 2.5% CEA, 3.8% TFCAS, 2.9% TCAR, P=0.054; late: 1.6% CEA, 2.8% TFCAS, 2.3% TCAR, P=0.003). TFCAS also had increased odds of in-hospital stroke/death compared with CEA in all 3 groups (urgent adjusted odds ratio [aOR], 1.7 [95% CI, 1.0-2.9] P=0.03; early aOR, 1.6 [95% CI, 1.1-2.4] P=0.01; and late aOR, 1.9 [95% CI, 1.2-3.0] P=0.01). TCAR and CEA had comparable odds of in-hospital stroke/death in all 3 groups (urgent aOR, 1.9 [95% CI, 0.9-4], P=0.10), (early aOR, 1.1 [95% CI, 0.7-1.7], P=0.66), (late aOR, 1.5 [95% CI, 0.9-2.3], P=0.08).ConclusionsCEA remains the safest method of revascularization within the urgent period. Among revascularization performed outside of the 48 hours, TCAR and CEA have comparable outcomes.

BackgroundEffective strategies are needed to facilitate the prompt diagnosis and treatment of tuberculosis in countries with a high burden of the disease.MethodsWe conducted a cluster-randomized trial in which Ugandan community health centers were assigned to a multicomponent diagnostic strategy (on-site molecular testing for tuberculosis, guided restructuring of clinic workflows, and monthly feedback of quality metrics) or routine care (on-site sputum-smear microscopy and referral-based molecular testing). The primary outcome was the number of adults treated for confirmed tuberculosis within 14 days after presenting to the health center for evaluation during the 16-month intervention period. Secondary outcomes included completion of tuberculosis testing, same-day diagnosis, and same-day treatment. Outcomes were also assessed on the basis of proportions.ResultsA total of 20 health centers underwent randomization, with 10 assigned to each group. Of 10,644 eligible adults (median age, 40 years) whose data were evaluated, 60.1% were women and 43.8% had human immunodeficiency virus infection. The intervention strategy led to a greater number of patients being treated for confirmed tuberculosis within 14 days after presentation (342 patients across 10 intervention health centers vs. 220 across 10 control health centers; adjusted rate ratio, 1.56; 95% confidence interval [CI], 1.21 to 2.01). More patients at intervention centers than at control centers completed tuberculosis testing (adjusted rate ratio, 1.85; 95% CI, 1.21 to 2.82), received a same-day diagnosis (adjusted rate ratio, 1.89; 95% CI, 1.39 to 2.56), and received same-day treatment for confirmed tuberculosis (adjusted rate ratio, 2.38; 95% CI, 1.57 to 3.61). Among 706 patients with confirmed tuberculosis, a higher proportion in the intervention group than in the control group were treated on the same day (adjusted rate ratio, 2.29; 95% CI, 1.23 to 4.25) or within 14 days after presentation (adjusted rate ratio, 1.22; 95% CI, 1.06 to 1.40).ConclusionsA multicomponent diagnostic strategy that included on-site molecular testing plus implementation supports to address barriers to delivery of high-quality tuberculosis evaluation services led to greater numbers of patients being tested, receiving a diagnosis, and being treated for confirmed tuberculosis. (Funded by the National Heart, Lung, and Blood Institute; XPEL-TB ClinicalTrials.gov number, NCT03044158.).

BackgroundSurgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.MethodsThis international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index 60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.FindingsOf eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16-30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77-0·84; p

ObjectiveThe current recommendations are to perform carotid endarterectomy within 2 weeks of symptoms for maximum long-term stroke prevention, although urgent carotid endarterectomy within 48 hours has been associated with increased perioperative stroke. With the development and rapid adoption of transcarotid artery revascularization (TCAR), we decided to study the effect of timing on the outcomes after TCAR.MethodsThe Vascular Quality Initiative database was searched for symptomatic patients who had undergone TCAR from September 2016 to November 2019. These patients were stratified by the interval to TCAR after symptom onset: urgent, within 48 hours; early, 3 to 14 days; and late, >14 days. The primary outcome was the in-hospital rate of combined stroke and death (stroke/death), evaluated using logistic regression analysis. The secondary outcome was the 1-year rate of recurrent ipsilateral stroke and mortality, evaluated using Kaplan-Meier survival analysis.ResultsA total of 2608 symptomatic patients who had undergone TCAR were included. The timing was urgent for 144 patients (5.52%), early for 928 patients (35.58%), and late for 1536 patients (58.90%). Patients undergoing urgent intervention had an increased risk of in-hospital stroke/death, which was driven primarily by an increased risk of stroke. No differences were seen for in-hospital death. On adjusted analysis, urgent intervention resulted in a threefold increased risk of stroke (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.2; P = .01) and a threefold increased risk of stroke/death (OR, 2.9; 95% CI, 1.3-6.4; P = .01) compared with late intervention. Patients undergoing early intervention had comparable risks of stroke (OR, 1.3; 95% CI, 0.7-2.3; P = .40) and stroke/death (OR, 1.2; 95% CI, 0.7-2.1; P = .48) compared with late intervention. On subset analysis, the type of presenting symptoms was an effect modifier. Patients presenting with stroke and those presenting with transient ischemic attack or amaurosis fugax both had an increased risk of stroke/death when undergoing urgent compared with late TCAR (OR, 2.7; 95% CI, 1.1-6.6; P = .04; and OR, 4.1; 95% CI, 1.1-15.0; P = .03, respectively). However only patients presenting with transient ischemic attack or amaurosis fugax had experienced an increased risk of stroke with urgent compared with late TCAR (OR, 5.0; 95% CI, 1.4-17.5; P < .01). At 1 year of follow-up, no differences were seen in the incidence of recurrent ipsilateral stroke (urgent, 0.7%; early, 0.2%; late, 0.1%; P = .13) or postdischarge mortality (urgent, 0.7%; early, 1.6%; late, 1.8%; P = .71).ConclusionsWe found that TCAR had a reduced incidence of stroke when performed 48 hours after symptom onset. Urgent TCAR within 48 hours of the onset of stroke was associated with a threefold increased risk of in-hospital stroke/death, with no added benefit for ≤1 year after intervention. Further studies are needed on long-term outcomes of TCAR stratified by the timing of the procedure.

PurposeTo examine how treatment delays brought on by the COVID-19 pandemic impacted the physical and emotional well-being of physicians treating these patients.MethodsA cross-sectional survey of physician breast specialists was posted from April 23rd to June 11th, 2020 on membership list serves and social media platforms of the National Accreditation Program for Breast Centers and the American Society of Breast Surgeons. Physician well-being was measured using 6 COVID-19 burnout emotions and the 4-item PROMIS short form for anxiety and sleep disturbance. We examined associations between treatment delays and physician well-being, adjusting for demographic factors, COVID-19 testing and ten COVID-19 pandemic concerns.Results870 physicians completed the survey, 61% were surgeons. The mean age of physicians was 52 and 548 (63.9%) were female. 669 (79.4%) reported some delay in patient care as a result of the COVID-19 pandemic. 384 (44.1%) and 529 (60.8%) of physicians scored outside normal limits for anxiety and sleep disturbance, respectively. After adjusting for demographic factors and COVID-19 testing, mean anxiety and COVID-19 burnout scores were significantly higher among physicians whose patients experienced either delays in surgery, adjuvant chemotherapy, radiation, breast imaging or specialty consultation. A multivariable model adjusting for ten physician COVID-19 concerns and delays showed that "delays will impact my emotional well-being" was the strongest concern associated with anxiety, sleep disturbance and COVID-19 burnout factors.ConclusionsBreast cancer treatment delays during the initial surge of the COVID-19 pandemic in the United States were associated with a negative impact on physician emotional wellness.

PurposeThe response to the COVID-19 pandemic has affected the management of patients with cancer. In this pooled retrospective analysis, we describe changes in management patterns for patients with cancer diagnosed with COVID-19 in two academic institutions in the San Francisco Bay Area.Materials and methodsAdult and pediatric patients diagnosed with COVID-19 with a current or historical diagnosis of malignancy were identified from the electronic medical record at the University of California, San Francisco, and Stanford University. The proportion of patients undergoing active cancer management whose care was affected was quantified and analyzed for significant differences with regard to management type, treatment intent, and the time of COVID-19 diagnosis. The duration and characteristics of such changes were compared across subgroups.ResultsA total of 131 patients were included, of whom 55 were undergoing active cancer management. Of these, 35 of 55 (64%) had significant changes in management that consisted primarily of delays. An additional three patients not undergoing active cancer management experienced a delay in management after being diagnosed with COVID-19. The decision to change management was correlated with the time of COVID-19 diagnosis, with more delays identified in patients treated with palliative intent earlier in the course of the pandemic (March/April 2020) compared with later (May/June 2020) (OR, 4.2; 95% CI, 1.03 to 17.3; P = .0497). This difference was not seen among patients treated with curative intent during the same timeframe.ConclusionWe found significant changes in the management of cancer patients with COVID-19 treated with curative and palliative intent that evolved over time. Future studies are needed to determine the impact of changes in management and treatment on cancer outcomes for patients with cancer and COVID-19.

BackgroundTrauma care providers often face a dilemma regarding anticoagulation therapy initiation in patients with traumatic brain injury owing to the associated risks of traumatic brain injury progression. The aims of this study were the following: (1) to describe the current practice of anticoagulation therapy in traumatic brain injury patients and their outcomes and (2) to identify factors associated with the progression of traumatic brain injury after anticoagulation therapy.MethodsIn this multicenter prospective observational study, we included computed tomography-proven traumatic brain injury patients who received anticoagulation therapy within 30 days of hospital admission. Our primary outcome was the incidence of clinically significant progression of traumatic brain injury after anticoagulation therapy initiation.ResultsA total of 168 patients were enrolled more than 22 months. Atrial fibrillation and venous thromboembolism were the most common pre-injury and postinjury anticoagulation therapy indications, respectively. Overall, 16 patients (9.6%) experienced clinically significant traumatic brain injury progression after anticoagulation therapy, out of which 9 (5.4%) patients subsequently required neurosurgical interventions. Between patients with clinical progression of traumatic brain injury and patients who showed no such progression, there were no significant differences in the baseline demographics and severity of traumatic brain injury. However, anticoagulation therapy was initiated significantly earlier in patients of the deterioration group than those of the no-deterioration group (4.5 days vs 11 days, P = .015). In a multiple logistic regression model, patients who received anticoagulation therapy later after injury had significantly lower risk of clinically significant traumatic brain injury progression (odds ratio: 0.915 for each day, 95% confidence interval: 0.841-0.995, P = .037).ConclusionOur results suggest that early anticoagulation therapy is associated with higher risk of traumatic brain injury progression, thus a balance between bleeding and thromboembolic risks should be carefully evaluated in each case before initiating anticoagulation therapy.

PurposeDelaying cataract surgery is associated with an increased risk of falls, but whether routine preoperative testing delays cataract surgery long enough to cause clinical harm is unknown. We sought to determine whether the use of routine preoperative testing leads to harm in the form of delayed surgery and falls in Medicare beneficiaries awaiting cataract surgery.DesignRetrospective, observational cohort study using 2006-2014 Medicare claims.ParticipantsMedicare beneficiaries 66+ years of age with a Current Procedural Terminology claim for ocular biometry.MethodsWe measured the mean and median number of days between biometry and cataract surgery, calculated the proportion of patients waiting ≥ 30 days or ≥ 90 days for surgery, and determined the odds of sustaining a fall within 90 days of biometry among patients of high-testing physicians (testing performed in ≥ 75% of their patients) compared with patients of low-testing physicians. We also estimated the number of days of delay attributable to high-testing physicians.Main outcome measuresIncidence of falls occurring between biometry and surgery, odds of falling within 90 days of biometry, and estimated delay associated with physician testing behavior.ResultsOf 248 345 beneficiaries, 16.4% were patients of high-testing physicians. More patients of high-testing physicians waited ≥ 30 days and ≥ 90 days to undergo surgery (31.4% and 8.2% vs. 25.0% and 5.5%, respectively; P < 0.0001 for both). Falls before surgery in patients of high-testing physicians increased by 43% within the 90 days after ocular biometry (1.0% vs. 0.7%; P < 0.0001). The adjusted odds ratio of falling within 90 days of biometry in patients of high-testing physicians versus low-testing physicians was 1.10 (95% confidence interval [CI], 1.03-1.19; P = 0.008). After adjusting for surgical wait time, the odds ratio decreased to 1.07 (95% CI, 1.00-1.15; P = 0.06). The delay associated with having a high-testing physician was approximately 8 days (estimate, 7.97 days; 95% CI, 6.40-9.55 days; P < 0.0001). Other factors associated with delayed surgery included patient race (non-White), Northeast region, ophthalmologist ≤ 40 years of age, and low surgical volume.ConclusionsOveruse of routine preoperative medical testing by high-testing physicians is associated with delayed surgery and increased falls in cataract patients awaiting surgery.

PurposeThe Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study's objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention.MethodsWe analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management.ResultsInfections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p = 0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p = 0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented.ConclusionInfants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS.Trial registrationNCT01186913.

BackgroundDelays in the diagnosis of tuberculosis (TB) contribute to a substantial proportion of TB-related mortality, especially among people living with HIV (PLHIV). We sought to characterize the diagnostic journey for HIV-positive and HIV-negative patients with a new TB diagnosis in Zambia, to understand drivers of delay, and characterize their preferences for service characteristics to inform improvements in TB services.MethodsWe assessed consecutive adults with newly microbiologically-confirmed TB at two public health treatment facilities in Lusaka, Zambia. We administered a survey to document critical intervals in the TB care pathway (time to initial care-seeking, diagnosis and treatment initiation), identify bottlenecks and their reasons. We quantified patient preferences for a range of characteristics of health services using a discrete choice experiment (DCE) that assessed 7 attributes (distance, wait times, hours of operation, confidentiality, sex of provider, testing incentive, TB test speed and notification method).ResultsAmong 401 patients enrolled (median age of 34 years, 68.7% male, 46.6% HIV-positive), 60.9% and 39.1% were from a first-level and tertiary hospital, respectively. The median time from symptom onset to receipt of TB treatment was 5.0 weeks (IQR: 3.6-8.0) and was longer among HIV-positive patients seeking care at a tertiary hospital than HIV-negative patients (6.4 vs. 4.9 weeks, p = 0.002). The time from symptom onset to initial presentation for evaluation accounted for the majority of time until treatment initiation (median 3.0 weeks, IQR: 1.0-5.0)-an important minority of 11.0% of patients delayed care-seeking ≥8 weeks. The DCE found that patients strongly preferred same-day TB test results (relative importance, 37.2%), facilities close to home (18.0%), and facilities with short wait times (16.9%). Patients were willing to travel to a facility up to 7.6 kilometers further away in order to access same-day TB test results. Preferences for improving current TB services did not differ according to HIV status.ConclusionsProlonged intervals from TB symptom onset to treatment initiation were common, especially among PLHIV, and were driven by delayed health-seeking. Addressing known barriers to timely diagnosis and incorporating patients' preferences into TB services, including same-day TB test results, may facilitate earlier TB care engagement in high burden settings.

BackgroundWe investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke.MethodsWe identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society.ResultsOf 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time (P = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes.ConclusionThe use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time.

BackgroundIn-hospital ST-elevation myocardial infarction (STEMI) is associated with a higher mortality rate than out-of-hospital STEMI. Quality measures and universal protocols for treatment of in-hospital STEMI do not exist, likely contributing to delays in recognition and treatment.HypothesisTo analyze differences in mortality among three subsets of patients who develop in-hospital STEMI.MethodsThis was a multicenter, retrospective observational study of patients who developed in-hospital STEMI at six United States medical centers between 2008 and 2017. Patients were stratified into three groups: (1) cardiac, (2) periprocedure, or (3) noncardiac/nonpostprocedure. Outcomes examined include time from electrocardiogram (ECG) acquisition to cardiac catheterization lab arrival (ECG-to-CCL) and survival to discharge.ResultsWe identified 184 patients with in-hospital STEMI (mean age 68.7 years, 58.7% male). Group 1 (cardiac) patients had a shorter average ECG-to-CCL time (69 minutes) than group 2 (periprocedure, 215 minutes) and group 3 (noncardiac/nonpostprocedure, 199 minutes). Compared to group 1, survival to discharge was lower for group 2 (OR 0.33, P = .102) and group 3 (OR 0.20, P = .016). After adjusting for prespecified covariates, the relationship between group and survival showed a similar trend but did not reach statistical significance.ConclusionsPatients who develop in-hospital STEMI in the context of a preceding procedure or noncardiac illness appear to have longer reperfusion times and higher in-hospital mortality than patients admitted with cardiac diagnoses. Larger studies are warranted to further investigate these observations. Health systems should place an increased emphasis on developing quality metrics and implementing quality improvement initiatives to improve outcomes for in-hospital STEMI.

BackgroundThe emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.MethodsThis study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.ResultsDuring the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p

Background/objectivesStandard supportive care during induction therapy for high-risk neuroblastoma (HR-NBL) includes primary prophylactic granulocyte colony-stimulating factor (G-CSF) aimed at limiting duration of neutropenia, reducing infection risk, and minimizing treatment delays. Preclinical models suggest that G-CSF promotes maintenance of neuroblastoma cancer stem cells and may reduce the efficacy of chemotherapy. This study's objective was to determine the safety and feasibility of administering induction chemotherapy without routine use of prophylactic G-CSF.Design/methodsChildren with newly diagnosed HR-NBL received six-cycle induction chemotherapy regimen without prophylactic G-CSF in four cycles. G-CSF was administered for stem cell mobilization after cycle 3 and granulocyte-monocyte colony-stimulating factor after cycle 5 prior to surgical resection of primary disease. The primary outcome measure was the incidence of grade 3 or higher infection. We hypothesized that the per patient infection rate would be comparable to our institutional baseline rate of 58% in patients with HR-NBL receiving induction chemotherapy with prophylactic growth factor support. The trial used an A'Hern single-stage design.ResultsTwelve patients with HR-NBL received 58 cycles of chemotherapy on study. Three patients completed the entire six-cycle regimen with no infections. Nine patients experienced grade 3 infections (bacteremia four, urinary tract infection two, skin/soft tissue infection three). No patients experienced grade 4 infections or required intensive care treatment for infection.ConclusionA greater than expected number of serious bacterial infections were observed during administration of induction chemotherapy for HR-NBL without primary prophylactic G-CSF. These results support continued prophylactic administration growth factor during induction chemotherapy.

PURPOSE: In oncology, chemotherapy treatment delays potentially jeopardize patient safety and impede progress toward disease remission. The purpose of this study was to examine the causes and consequences of chemotherapy treatment delays and possible solutions to improve quality of care. PARTICIPANTS & SETTING: The current authors selected a purposive sample of eight ambulatory oncology practices for ethnographic site visits, which lasted five days each. METHODOLOGIC APPROACH: The authors conducted 290 observation hours, including clinician shadowing, and 46 semistructured interviews with clinicians (oncology nurses, physicians, and advanced practice providers). Deductive and inductive thematic analysis was performed on all data. FINDINGS: The authors identified four primary themes from the analysis that affect delays. IMPLICATIONS FOR NURSING: Future investigations should examine nurses communication practices in the context of timely chemotherapy administration because communication and documentation technologies within healthcare settings continuously evolve.

BackgroundNon-Hispanic black (NHB) and Hispanic patients have lower access to kidney transplantation compared to non-Hispanic whites (NHWs). We examined whether differences in the prevalence of comorbidities that affect eligibility for transplant contribute to disparities in receipt of transplantation.MethodsWe performed a retrospective study of 986 019 adults who started dialysis between 2005 and 2014, according to the United States Renal Data System. We compared prevalence of comorbidities that could influence transplant eligibility by race/ethnicity. We examined time to first transplant by race/ethnicity in this overall cohort and in a very healthy sub-cohort without conditions that could be contraindications to transplantation.ResultsDuring 2.3 years of mean follow-up, 64 892 transplants occurred. NHBs and Hispanics had a lower prevalence of medical barriers to transplantation at the time of dialysis initiation than NHWs, including age >70 years (26% in NHB versus 47% in NHW) and malignancy (4% in Hispanics versus 10% in NHWs). Access to transplant was 65% lower (95% CI, 0.33-0.37) in NHBs and 43% lower (95% CI, 0.54-0.62) in Hispanics (versus NHWs) in the first year after end-stage renal disease, but by Year 4, access to transplantation was not statistically significantly different between Hispanics or NHBs (versus NHWs). In our very healthy cohort, racial and ethnic disparities in access to transplantation persisted up to Year 5 in NHBs and Year 4 in Hispanics after end-stage renal disease onset.ConclusionsDifferences in medical eligibility do not appear to explain racial/ethnic disparities in receipt of kidney transplantation and may mask the actual magnitude of the inequities that are present.

ObjectiveStudies evaluating major amputation after initial minor amputation are few with rates of subsequent major amputation ranging from 14% to 35% with limited understanding of associated comorbidities and time to limb loss. The aim of this study is to determine the major amputation rates for patients who had already undergone an initial minor amputation and determine which factors are associated with the need for subsequent major amputation.MethodsUsing statewide data between 2005 and 2013, patients with peripheral artery disease (PAD), diabetes mellitus (DM), and combined PAD/DM who had a lower extremity ulcer and who had also undergone a minor amputation were identified. These patients were evaluated for the rate of subsequent major amputation and competing risk Cox proportional hazards modeling was used to study which factors were associated with the risk of subsequent limb loss.ResultsThe cohort consisted of 11,597 patients (DM, n = 4254; PAD, n = 2142; PAD/DM, n = 5201) with lower extremity ulcers who underwent an initial minor amputation. The rate of any subsequent amputation was highest in patients with PAD/DM (23% vs DM = 17%, PAD = 17%; P = not statistically significant). The rate of subsequent minor amputation was 16% in the PAD/DM versus 15.2% in PAD and 12.2% in patients with DM (P < .001). Patients with PAD/DM had the highest rate of subsequent major amputation (6.3% vs DM = 5.2%, PAD = 2.1%; P < .001). There was no statistically significant difference in the median time to major amputation among the three groups (PAD/DM, 13 months; DM, 14 months; PAD, 8.6 months; P = NS). Patients who were revascularized before a repeat minor amputation had a decreased risk of a major amputation compared with those who were intervened on after a repeat minor amputation (hazard ratio, 0.002; 95% confidence interval, 0-0.22). Patients treated completely in the outpatient setting were also less likely to undergo subsequent major amputation (hazard ratio, 0.7; 95% confidence interval, 0.5-0.98) compared with those who required hospitalization or presented to the emergency room.ConclusionsPatients with ulcers and combined PAD and DM have a higher risk for secondary major and minor amputation than patients with either disease alone with half of the limb loss occurring at approximately 1 year after the initial minor amputation. Additionally, early diagnosis and appropriate referral may result in decreased limb loss for these patients.

BACKGROUND: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. METHODS: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. FINDINGS: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31-62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46-0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17-2·81) and pelvic (1·35, 1·10-1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. INTERPRETATION: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. FUNDING: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

BackgroundPatients with knee osteoarthritis may undergo total knee replacement too early or may delay or underuse this procedure. We quantified these categories of total knee replacement utilization in 2 cohorts of participants with knee osteoarthritis and investigated factors associated with each category.MethodsData were pooled from 2 multicenter cohort studies that collected demographic, patient-reported, radiographic, clinical examination, and total knee replacement utilization information longitudinally on 8,002 participants who had or were at risk for knee osteoarthritis and were followed for up to 8 years. Validated total knee replacement appropriateness criteria were longitudinally applied to classify participants as either potentially appropriate or likely inappropriate for total knee replacement. Participants were further classified on the basis of total knee replacement utilization into 3 categories: timely (indicating that the patient had total knee replacement within 2 years after the procedure had become potentially appropriate), potentially appropriate but knee not replaced (indicating that the knee had remained unreplaced for >2 years after the procedure had become potentially appropriate), and premature (indicating that the procedure was likely inappropriate but had been performed). Utilization rates were calculated, and factors associated with each category were identified.ResultsAmong 8,002 participants, 3,417 knees fulfilled our inclusion and exclusion criteria and were classified into 1 of 3 utilization categories as follows: 290 knees (8% of the total and 9% of the knees for which replacement was potentially appropriate) were classified as "timely", 2,833 knees (83% of the total and 91% of those for which replacement was potentially appropriate) were classified as "potentially appropriate but not replaced", and 294 knees (comprising 9% of the total and 26% of the 1,114 total knee replacements performed) were considered to be "likely inappropriate" yet underwent total knee replacement and were classified as "premature". Of the knees that were potentially appropriate but were not replaced, 1,204 (42.5%) had severe symptoms. Compared with the patients who underwent timely total knee replacement, the likelihood of being classified as potentially appropriate but not undergoing total knee replacement was greater for black participants and the likelihood of having premature total knee replacement was lower among participants with a body mass index of >25 kg/m and those with depression.ConclusionsIn 2 multicenter cohorts of patients with knee osteoarthritis, we observed substantial numbers of patients who had premature total knee replacement as well as of patients for whom total knee replacement was potentially appropriate but had not been performed >2 years after it had become potentially appropriate. Further understanding of these observations is needed, especially among the latter group.Clinical relevanceUndergoing total knee replacement too early may result in little or no benefit while exposing the patient to the risks of a major operation, whereas waiting too long may cause limitations in physical activity that in turn increase the risk of additional disability and chronic disease; however, little is known about timing of this surgery. We quantified the extent of premature, timely, and delayed use, and found a high prevalence of both premature and delayed use.

BackgroundA decision to delay seeking treatment for symptoms of acute coronary syndrome increases the risk of serious complications, disability, and death.AimsThe purpose of this study was to determine if there was an association between gradual vs abrupt symptom onset and prehospital delay for patients with acute coronary syndrome and to examine the relationship between activities at symptom onset and gradual vs abrupt symptom onset.MethodsThis was a secondary analysis of a large prospective multi-center study. Altogether, 474 patients presenting to the emergency department with symptoms of acute coronary syndrome were included in the study. Symptom characteristics, activity at symptom onset, and prehospital delay were measured with the ACS Patient Questionnaire.ResultsMedian prehospital delay time was four hours. Being uninsured (β=0.120, p=0.031) and having a gradual onset of symptoms (β=0.138, p=0.003) were associated with longer delay. A diagnosis of ST-elevation myocardial infarction (β=-0.205, p=0.001) and arrival by ambulance (β=-0.317, p

IntroductionAchieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan Africa (SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign.DiscussionThese three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved >90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted in marked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in which mortality was comprehensively measured.ConclusionsThese trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets.

BACKGROUND: Socioeconomic status (SES) is associated with diagnostic and treatment delays and survival in multiple cancers, but less data exist for anal squamous cell carcinoma (ASCC). This study investigated the association between SES and outcomes for patients undergoing definitive chemoradiation therapy for ASCC. METHODS: One hundred and eleven patients diagnosed with nonmetastatic ASCC between 2005 and 2018 were retrospectively reviewed. Socioeconomic predictor variables included primary payer, race, income, employment, and partnership status. Outcomes included the tumor-node (TN) stage at diagnosis, the duration from diagnosis to treatment initiation, relapse-free survival (RFS), and overall survival (OS). Age, gender, TN stage, and HIV status were analyzed as covariates in survival analysis. RESULTS: SES was not associated with the TN stage at diagnosis. SES factors associated with treatment initiation delays were Medicaid payer (P = .016) and single partnership status (P = .016). Compared to privately insured patients, Medicaid patients had lower 2-year RFS (64.4% vs 93.8%, P = .021) and OS (82.9% vs 93.5%, P = .038). Similarly, relative to patients in the racial majority, racial minority patients had lower 2-year RFS (53.3% vs 93.5%, P = .001) and OS (73.7% vs 92.6%, P = .008). Race was an independent predictor for both RFS (P = .027) and OS (P = .047). CONCLUSIONS: These results highlight the impact of social contextual factors on health. Interventions targeted at socioeconomically vulnerable populations are needed to reduce disparities in ASCC outcomes.

BackgroundEvidence indicates the unmet need for primary care services including medical, mental health, and dental care is greater among uninsured and Medicaid beneficiaries than privately insured individuals, many of whom use Health Resources and Services Administration-funded health centers (HRSA HCs).ObjectiveWe examined differences in rates of unmet need between low-income uninsured and Medicaid patients of HRSA HCs and safety-net clinics in general or private physicians.Research designWe used logistic regression models to compare the predicted probabilities of unmet need for uninsured and Medicaid individuals whose usual source of care is HRSA HCs versus clinics in general or private physicians.SampleWe used a nationally representative survey of low income, adult patients who identified HRSA HCs as their usual source of care. We used the National Health Interview Survey to independently identify low-income individuals whose usual source of care was clinics (National Health Interview Survey clinics) or physicians (National Health Interview Survey physicians) in the general population.MeasuresDependent variables were unmet need and delay in medical care, and unmet need for prescription medications, mental health, and dental care. The primary independent variable of interest was the usual source of care. We controlled for potential confounders.ResultsWe found the probability of unmet need for medical and dental care to be lower among HRSA HC patients than individuals whose usual source of care were not HRSA HCs.ConclusionsHRSA HC patients have lower probabilities of unmet need for medical and dental care. This is likely because HRSA HCs provide accessible, affordable, and comprehensive primary care services. Expanding capacity of these organizations will help reduce unmet need and its consequences.

BackgroundHepatitis C virus (HCV) infection is increasingly prevalent among people who inject drugs (PWID) in the context of the current US opioid crisis. Although curative therapy is available and recommended as a public health strategy, few PWID have been treated. We explore PWID narratives that explain why they have not sought HCV treatment or decided against starting it. We then compare these narratives to evidence-based and guideline-concordant information to better enable health, social service, harm reduction providers, PWID, and other stakeholders to dispel misconceptions and improve HCV treatment uptake in this vulnerable population.MethodsWe recruited HIV-uninfected PWID (n = 33) through community-based organizations (CBOs) to participate in semi-structured, in-depth qualitative interviews on topics related to overall health, access to care, and knowledge and interest in specific HIV prevention methods.ResultsIn interviews, HCV transmission and delaying or forgoing HCV treatment emerged as important themes. We identified three predominant narratives relating to delaying or deferring HCV treatment among PWID: (1) lacking concern about HCV being serious or urgent enough to require treatment, (2) recognizing the importance of treatment but nevertheless deciding to delay treatment, and (3) perceiving that clinicians and insurance companies recommend that patients who currently use or inject drugs should delay treatment.ConclusionsOur findings highlight persistent beliefs among PWID that hinder HCV treatment utilization. Given the strong evidence that treatment improves individual health regardless of substance use status while also decreasing HCV transmission in the population, efforts are urgently needed to counter the predominant narratives identified in our study. We provide evidence-based, guideline-adherent information that counters the identified narratives in order to help individuals working with PWID to motivate and facilitate treatment access and uptake. An important strategy to improve HCV treatment initiation among PWID could involve disseminating guideline-concordant counternarratives to PWID and the providers who work with and are trusted by this population.

BACKGROUND:The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke is time dependent. Despite great effort, the median door-to-needle time (DNT) was 60 min at the United States stroke centers. We investigated the effect of a simple quality improvement initiative on DNT for IVT. METHODS:This is a single-center study of patients treated with IVT between 2013 and 2017. A simple quality improvement initiative was implemented in January 2015 to allow the Stroke team to manage hypertension in the emergency room, to make decision for IVT before getting blood test results unless patients were taking oral anticoagulants, and to give IVT in the CT suite. Baseline characteristics, DNT and outcomes at hospital discharge were compared between pre- and post-intervention groups. RESULTS:Ninety and 136 patients were treated with IVT in pre- and post-intervention groups, respectively. The rate of IVT was significantly higher in the post-intervention group (20% vs. 14.4%, p = 0.007). The median DNT with interquartile range (IQR) was reduced significantly by 23 min (63[53-81] vs. 40[29-53], p

BackgroundDiagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP).MethodsA retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT.ResultsOne hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03-4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles.ConclusionsDeterminants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting.

BackgroundChronic immune activation in the blood and central nervous system is a consequence of human immunodeficiency virus (HIV) infection that contributes to disease morbidity and can occur despite virally suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined immune activation markers in cerebrospinal fluid (CSF) and blood specimens collected over 96 weeks from participants who initiated ART during acute HIV infection (AHI).MethodsRV254/SEARCH010 study participants with AHI underwent CSF (n = 89) and plasma (n = 146) sampling before initiating ART and at weeks 24 and 96 of treatment. A majority participants (64.4%) received a standard ART regimen (hereafter, "standard ART"), with some (34.7%) also receiving maraviroc and raltegravir for the first 24 weeks (hereafter, "ART plus"). We compared neopterin, CXCL10, CCL2, and interleukin 6 (IL-6) levels in the AHI group to those in 18 healthy, uninfected controls.ResultsFollowing 24 and 96 weeks of treatment, levels of all CSF markers normalized while levels of several plasma markers remained elevated in the AHI group (P < .001). Participants receiving the ART-plus regimen had lower median plasma CCL2 levels at week 24 and lower plasma neopterin levels at week 96.ConclusionsART initiation during AHI differentially impacts the brain compartment, with markers of inflammation returning to normal levels in the CSF, where they were sustained at week 96, but not in plasma.

BackgroundImpaired postinjury platelet aggregation is common, but the effect of transfusion on this remains unclear. Data suggest that following injury platelet transfusion may not correct impaired platelet aggregation, and impaired platelet aggregation may not predict the need for platelet transfusion. We sought to further investigate platelet aggregation responses to transfusions, using regression statistics to isolate the independent effects of transfusions given in discrete time intervals from injury on both immediate and longitudinal platelet aggregation. We hypothesized that platelet aggregation response to platelet transfusion increases over time from injury.MethodsSerial (0-96 hours) blood samples were collected from 248 trauma patients. Platelet aggregation was assessed in vitro with impedance aggregometry stimulated by adenosine diphosphate, collagen, and thrombin receptor-activating peptide-6. Using regression, transfusion exposure was modeled against platelet aggregation at each subsequent timepoint and adjusted for confounders (Injury Severity Score, international normalized ratio (INR), base deficit, platelet count, and interval transfusions). The expected change in platelet aggregation at each timepoint under the intervention of transfusion exposure was calculated and compared with the observed platelet aggregation.ResultsThe 248 patients analyzed were severely injured (Injury Severity Score, 21 ± 19), with normal platelet counts (mean, 268 × 10/L ± 90), and 62% were transfused in 24 hours. The independent effect of transfusions on subsequent platelet aggregation over time was modeled with observed platelet aggregation under hypothetical treatment of one unit transfusion of blood, plasma, or platelets. Platelet transfusions had increasing expected effects on subsequent platelet aggregation over time, with the maximal expected effect occurring late (4-5 days from injury).ConclusionControversy exists on whether transfusions improve impaired postinjury platelet aggregation. Using regression modeling, we identified that expected transfusion effects on subsequent platelet aggregation are maximal with platelet transfusion given late after injury. This is critical for tailored resuscitation, identifying a potential early period of resistance to platelet transfusion that resolves by 96 hours.Level of evidenceTherapeutic, level V.

ObjectiveTo determine whether lower socioeconomic status (SES) and longer home to hospital driving time are associated with reductions in tissue plasminogen activator (tPA) administration and timeliness of the treatment.MethodsWe conducted a retrospective observational study using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between January 2015 and March 2017. The study included 118,683 ischemic stroke patients age ≥18 who were transported by emergency medical services to one of 1,489 US hospitals. We defined each patient's SES based on zip code median household income. We calculated the driving time between each patient's home zip code and the hospital where he or she was treated using the Google Maps Directions Application Programing Interface. The primary outcomes were tPA administration and onset-to-arrival time (OTA). Outcomes were analyzed using hierarchical multivariable logistic regression models.ResultsSES was not associated with OTA (p = 0.31) or tPA administration (p = 0.47), but was associated with the secondary outcomes of onset-to-treatment time (OTT) (p = 0.0160) and in-hospital mortality (p = 0.0037), with higher SES associated with shorter OTT and lower in-hospital mortality. Driving time was associated with tPA administration (p < 0.001) and OTA (p < 0.0001), with lower odds of tPA (0.83, 0.79-0.88) and longer OTA (1.30, 1.24-1.35) in patients with the longest vs shortest driving time quartiles. Lower SES quintiles were associated with slightly longer driving time quartiles (p = 0.0029), but there was no interaction between the SES and driving time for either OTA (p = 0.1145) or tPA (p = 0.6103).ConclusionsLonger driving times were associated with lower odds of tPA administration and longer OTA; however, SES did not modify these associations.

PURPOSE: Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs. PATIENTS AND METHODS: Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs. RESULTS: Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib (P = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; P < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; P < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank P = .01) and overall survival (log-rank P < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications. CONCLUSION: CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.

All patients with hepatocellular carcinoma meeting United Network for Organ Sharing T2 criteria currently receive the same listing priority for liver transplant (LT). A previous study from our center identified a subgroup with a very low risk of waitlist dropout who may not derive immediate LT benefit. To evaluate this issue at a national level, we analyzed within the United Network for Organ Sharing database 2052 patients with T2 hepatocellular carcinoma receiving priority listing from 2011 to 2014 in long wait time regions 1, 5, and 9. Probabilities of waitlist dropout were 18.3% at 1 year and 27% at 2 years. In multivariate analysis, factors associated with a lower risk of waitlist dropout included Model for End-Stage Liver Disease-Na

Background & aimsEarly liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH.MethodsWe developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant.ResultsPatients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores.ConclusionsIn a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.

We examined correlates of late and delayed initiation of antiretroviral therapy (ART) in British Columbia, Canada. From December 2013 to December 2015 we recruited treatment-naïve people living with HIV who initiated ART within the previous year. 'Late initiation' was defined as CD4 cell count ≤500 cells/µL at ART initiation and 'delayed initiation' as ≥1 year between HIV diagnosis and initiation. Multivariable logistic regression assessed independent correlates of late and delayed initiation. Of 87 participants, 44 (51%) initiated late and 22 (26%) delayed initiation. Delayed initiation was positively associated with older age (adjusted odds ratio [AOR]: 1.06 per year, 95% confidence interval [95% CI]: 1.01-1.12) and inversely associated with wanting to start ART at diagnosis (AOR: 0.06, 95% CI: 0.02-0.21). Variables associated with late initiation were older age (AOR: 1.09 per year, 95% CI: 1.03-1.15) and medical reason(s) for initiation (AOR: 5.00, 95% CI: 1.41-17.86). Late initiation was less likely among those with greater perceived ART efficacy (AOR 0.94, 95% CI: 0.90-0.98) and history of incarceration (AOR: 0.12, 95% CI: 0.03-0.56). Disparities in timing of initiation were observed for age, perceived ART efficacy, and history of incarceration. Enhanced health services that address these factors may facilitate earlier treatment initiation.

IntroductionAmong patients with psychotic disorders, the 'duration of untreated psychosis' (DUP) is a predictor of key outcomes such as symptom remission and quality of life. In sub-Saharan Africa, DUP is up to five times longer than in high-income countries, with many patients going without antipsychotic medication for 5 years or longer. One contributor to this high DUP may relate to cultural norms that drive use of alternative and complementary therapies (ACTs) as first-line treatment strategies, rather than biomedical care with antipsychotic medicine. We aim to1 determine the prevalence and factors associated with DUP and ACT use in Uganda, and2 Identify factors that drive patient and family choices to use ACT as a first-line treatment strategy.Methods and analysisWe will leverage on an ongoing cohort study at the national psychiatric and teaching hospital in Uganda. The parent study is an observational cohort design following antipsychotic naïve adults with a first episode of psychosis without substance use, HIV/AIDS or syphilis. The embedded study will use a mixed methods design including quantitative assessment of parent study participants with the Nottingham Onset Schedule-DUP to determine the DUP. Qualitative assessment will focus on patient and caregiver perceptions and use of ACT and its impact on DUP among patients with psychosis using in-depth interviews.Ethics and disseminationThe study has received ethical approval from the school of medicine research and ethics committee of the college of health sciences at Makerere University. It has also received institutional support to perform the study from the Infectious Diseases Institute and Butabika hospital. Besides publication of the work in reputable peer-reviewed journals, we hope that this work will lead to evidence-based discussions on the need for early interventions to reduce DUP in Uganda.

Functional impairment is associated with mortality in adult liver transplant candidates. This has not been studied in pediatric liver transplant candidates. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to investigate functional status, waitlist mortality, and posttransplant outcomes in children younger than 18 years who were waitlisted in 2006-2016 for primary liver transplant. Functional status was categorized, by using the Lansky Play-Performance Scale (LPPS), as normal/good (80-100), moderately impaired (50-70), or severely impaired (10-40) by center assessment. Among 3250 children not listed as Status 1A, 62% had an LPPS score of 80-100, 25% had a score of 50-70, and 13% had a score of 10-40 at listing. Children with an LPPS score of 10-40 at listing were more likely to die while on the waitlist (standardized hazard ratio 1.85, 95% confidence interval 1.09-3.13, P = .02) in analyses adjusting for being on a ventilator, breathing support, or dialysis and other illness severity measures. For the 2565 children transplanted, an LPPS score of 10-40 at listing drastically increased mortality risk by 1 year posttransplant (hazard ratio 5.77, 95% confidence interval 3.05-10.91, P

Acute-on-chronic liver failure (ACLF) characterized with ≥2 extrahepatic organ failures in cirrhosis carries a high mortality. Outcomes of patients listed for liver transplantation (LT) after ACLF and after LT are largely unknown. The North American Consortium for the Study of End-Stage Liver Disease prospectively enrolled 2793 nonelectively hospitalized patients with cirrhosis; 768 were listed for LT. Within 3 months, 265 (35%) received a LT, 395 remained alive without LT, and 108 died/delisted. Compared with nonlisted patients, those listed were younger and more often had ACLF, acute kidney injury, and a higher admission Model for End-Stage Liver Disease (MELD) score. ACLF was most common in patients who died/delisted, followed by those alive with and without LT respectively, (30%, 22%, and 7%, respectively; P

BackgroundThe impact of treatment delays on prostate cancer-specific outcomes remains ill-defined. This study investigates the effect of time to treatment on biochemical disease control after prostatectomy.MethodsThis retrospective study includes 1,807 patients who received a prostatectomy as a primary treatment at two large tertiary referral centers from 1987 to 2015. Multivariate cox model with restricted cubic spline was used to identify optimal time to receive treatment and estimate the risk of biochemical recurrence.ResultsMedian follow-up time of the study was 46 (interquartile range, 18-86) months. Time to treatment was subcategorized based on multivariate cubic spline cox model. In multivariate spline model, adjusted for all the pertinent pretreatment variables, inflection point in the risk of biochemical recurrence was observed around 3 months, which further increased after 6 months. Based on spline model, time to treatment was then divided into 0 to 3 months (61.5%), >3 to 6 months (31.1%), and 6 months (7.4%). In the adjusted cox model, initial delays up to 6 months did not adversely affect the outcome; however, time to treatment >6 months had significantly higher risk of biochemical recurrence (HR, 1.84; 95% confidence interval, 1.30-2.60; P < 0.01).ConclusionsThe initial delays up to 6 months in prostate cancer primary treatment may be sustainable without adversely affecting the outcome. However, significant delays beyond 6 months can unfavorably affect biochemical disease control.ImpactTime to treatment can aid clinicians in the decision-making of prostate cancer treatment recommendation and educate patients against unintentional treatment delays.

AIM:Although recent out-of-hospital cardiac arrest (CA) trials found no benefits of hypothermia versus normothermia targeted temperature management, preclinical models suggest earlier timing of hypothermia improves neuroprotective efficacy. This study investigated whether shorter time to goal temperature was associated with better one-year outcomes in the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital Trial. METHODS:Patients were classified by tertiles of time to attain assigned goal temperature range (32-34°C or 36-37.5°C) following ROSC. Outcomes in the first tertile ("earlier") Group 1 were compared with second and third tertiles ("later") Group 2. Separate analyses were, additionally, completed for hypothermia and normothermia intervention groups. Three one-year outcomes were examined: survival; Vineland Adaptive Behavior Scale (VABS-II) score≥70; and decrease in VABS-II≤15 points from baseline. RESULTS:In the entire cohort (n=281), median time from ROSC to goal temperature was 7.4 [IQR 6.2-9.7] hours: Group 1, 5.8 [IQR 5.2, 6.2] and Group 2, 8.8 [IQR 7.4, 10.4] h. Outcomes did not differ between these groups. For hypothermia subgroup, survival was lower in Group 1 than 2, [10/49(20%) versus 47/99(47%), p

BackgroundXpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF.MethodsWe searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394.FindingsOur search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68-1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65-1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60-0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2

BackgroundPatients treated at 24/7 percutaneous coronary intervention (PCI) centres following out-of-hospital cardiac arrest (OHCA) have better outcomes than those treated at non-24/7 PCI centres. However, variation in outcomes between 24/7 PCI centres is not well studied.ObjectivesTo evaluate variation in outcomes among 24/7 PCI centres and to assess stability of 24/7 PCI centre performance.MethodsAdult patients in the California Office of Statewide Health Planning and Development Patient Discharge Database with a "present on admission" diagnosis of cardiac arrest admitted to a 24/7 PCI centre from 2011 to 2015 were included. Primary outcome was good neurologic recovery at hospital discharge. Secondary outcomes were survival to hospital discharge, cardiac catheterisation, and DNR orders within 24 h. Data were analysed using mixed effects logistic regression models. Hospitals were ranked each year and overall.ResultsOf 27,122 patients admitted to 128 24/7 PCI centres, 41% (11,184) survived and 27% (7188) had good neurologic recovery. Adjusted rates of good neurologic recovery (18%-39%; p,0.001), survival (32%-51%; p

BACKGROUND:Studies of the timing of end-stage renal disease (ESRD) have primarily defined "early" versus "late" initiation of dialysis using estimated glomerular filtration rate (eGFR)-based criteria. Our objective was to determine the theoretical time that could be spent in chronic kidney disease (CKD) stage 5 prior to reaching a conservative eGFR threshold of 5 mL/min/1.73 m2 compared to the actual time spent in CKD stage 5 by risk factors of interest. METHODS:Eight-hundred and seventy Chronic Renal Insufficiency Cohort participants with CKD stage 5 who started renal replacement therapy (RRT) were included for retrospective study. We used mixed models to estimate the person-specific trajectory of renal function. We then used these individual trajectories to estimate the amount of time that would be spent in CKD stage 5 (between eGFR of 15 and 5 mL/min/1.73 m2) and compared this estimate to the actual time spent in CKD stage 5 prior to ESRD (between eGFR of 15 mL/min/1.73 m2 and ESRD). RESULTS:We found the median observed time between eGFR of 15 mL/min/1.73 m2 to RRT was 9.6 months, but the median predicted time between eGFR of 15 mL/min/1.73 m2 to eGFR of 5 mL/min/1.73 m2 was 17.7 months. Some of the largest differences between the predicted and actual amount of time spent in CKD stage 5 were noted among those with systolic blood pressure

BackgroundClinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment.MethodsWe prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection.ResultsOver a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83-97%) and specificity of 95% (92-98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empirically-treated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L).ConclusionJudged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses.

ImportanceDe novo statin therapy in patients receiving chronic dialysis has failed to demonstrate cardiovascular (CV) protection in randomized clinical trials and thus is not recommended by current guidelines. However, current guidelines recommend the continuation of statin therapy if initiated before transition to dialysis.ObjectiveTo investigate whether the continuation of statins from advanced chronic kidney disease into the dialysis therapy period is associated with improved survival.Design, setting, and participantsRetrospective cohort study of US veterans transitioning to dialysis between October 1, 2007, and March 30, 2014. Participants were 14 298 US veterans who were receiving statins during the 12-month period before transition to dialysis and survived the first year of dialysis. Data analysis was conducted between August 2, 2017, and June 28, 2018.ExposuresPatients were characterized as statin continuers (n = 11 936) if statin therapy was continued for at least 6 months during the first year after dialysis initiation and as statin discontinuers (n = 2362) if therapy with statins was stopped or no statin therapy was received in the year posttransition.Main outcomes and measuresAssociations of statin continuation with 12-month all-cause mortality and CV mortality after 1 year of dialysis initiation were examined using Cox proportional hazards regression models adjusted for demographics and comorbidities.ResultsThe mean (SD) age of the cohort was 71 (10) years; the cohort was 96.7% (n = 13 828) male and 21.3% (n = 3043) African American, and 74.6% (n = 10 627) had diabetes. The 12-month all-cause mortality and CV mortality rates after 1 year of transition to dialysis were lower in statin continuers: deaths per 100 person-years were 21.9 (95% CI, 20.9-22.8) and 8.1 (95% CI, 7.5-8.6) in statin continuers vs 30.3 (95% CI, 27.8-32.8) and 9.8 (95% CI, 8.3-11.2) in statin discontinuers. Moreover, lower all-cause mortality and CV mortality risks with statin continuation persisted in adjusted analyses, with hazard ratios of 0.72 (95% CI, 0.66-0.79) and 0.82 (95% CI, 0.69-0.96), respectively. Associations were similar across subgroups, including age, race, and diabetes status.Conclusions and relevanceIn this study, the continuation of statin therapy after transition to dialysis was associated with reduced all-cause mortality and CV mortality. The study findings suggest that future studies are needed to examine potential CV benefits of continuing statin therapy after dialysis initiation.

Given the increasing incidence of hepatocellular carcinoma (HCC) and regional variation in liver transplantation (LT) rates for HCC, we investigated temporal and geographic disparities in LT and wait-list dropout. LT candidates receiving Model for End-Stage Liver Disease (MELD) exception from 2005 to 2014 were identified from the United Network for Organ Sharing database (n = 14,320). Temporal differences were compared across 2 eras (2005-2009 and 2010-2014). Regional groups were defined based on median wait time as long-wait region (LWR; regions 1, 5, and 9), mid-wait region (MWR; regions 2, 4, 6, 7, and 8), and short-wait region (SWR; regions 3, 10, and 11). Fine and Gray competing risk regression estimated risk of wait-list dropout as hazard ratios (HRs). The cumulative probability of LT within 3 years was 70% in the LWR versus 81% in the MWR and 91% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, median time to LT increased by 6.0 months (5.6 to 11.6 months) in the LWR compared with 3.8 months (2.6 to 6.4 months) in the MWR and 1.3 months (1.0 to 2.3 months) in the SWR. The cumulative probability of dropout within 3 years was 24% in the LWR versus 16% in the MWR and 8% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, the LWR also had the greatest increase in probability of dropout. Risk of dropout was increased in the LWR (HR, 3.5; P < 0.001) and the MWR (HR, 2.2; P < 0.001) compared with the SWR, and year of MELD exception 2010-2014 (HR, 1.9; P < 0.001) compared with 2005-2009. From 2005-2009 to 2010-2014, intention-to-treat 3-year survival decreased from 69% to 63% in the LWR (P < 0.001), 72% to 69% in the MWR (P = 0.008), and remained at 74% in the SWR (P = 0.48). In conclusion, we observed a significant increase in wait-list dropout in HCC patients in recent years that disproportionately impacted LWR patients. Widening geographical disparities call for changes in allocation policy as well as enhanced efforts at increasing organ donation and utilization.

BackgroundThe Institute of Medicine emphasizes care timeliness as an important quality metric. We assessed treatment timeliness in stage I-IIIA lung cancer patients deemed eligible for curative intent therapy and analyzed the relationship between time to treatment (TTT) and timely treatment (TT) with survival.MethodsWe retrospectively reviewed consecutive cases of stage I-IIIA lung cancer deemed eligible for curative intent therapy at the VA San Diego Healthcare System between 10/2010-4/2017. We defined TTT as days from chest tumor board to treatment initiation and TT using guideline recommendations. We used multivariable (MVA) Cox proportional hazards regressions for survival analyses.ResultsIn 177 veterans, the median TTT was 35 days (29 days for chemoradiation, 36 for surgical resection, 42 for definitive radiation). TT occurred in 33% or 77% of patients when the most or least timely guideline recommendation was used, respectively. Patient characteristics associated with longer TTT included other cancer history, high simplified comorbidity score, stage I disease, and definitive radiation treatment. In MVA, TTT and TT [HR 0.53 (95% CI 0.27, 1.01) for least timely definition] were not associated with OS in stage I-IIIA patients, or disease-free survival in subgroup analyses of 122 stage I patients [HR 1.49 (0.62, 3.59) for least timely definition].ConclusionTreatment was timely in 33-77% of veterans with lung cancer deemed eligible for curative intent therapy. TTT and TT were not associated with survival. The time interval between diagnosis and treatment may offer an opportunity to deliver or improve other cancer care.