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BACKGROUND: Following a breast cancer diagnosis, it is uncertain whether womens breast density knowledge influences their willingness to undergo pre-operative imaging to detect additional cancer in their breasts. We evaluated womens breast density knowledge and their willingness to delay treatment for pre-operative testing. METHODS: We surveyed women identified in the Breast Cancer Surveillance Consortium aged ≥ 18 years, with first breast cancer diagnosed within the prior 6-18 months, who had at least one breast density measurement within the 5 years prior to their diagnosis. We assessed womens breast density knowledge and correlates of willingness to delay treatment for 6 or more weeks for pre-operative imaging via logistic regression. RESULTS: Survey participation was 28.3% (969/3,430). Seventy-two percent (469/647) of women with dense and 11% (34/322) with non-dense breasts correctly knew their density (p

Objective: To identify factors associated with delays in beginning adjuvant therapy and prognosis impacts on non‐metastatic breast cancer patients. Methods: This assessment comprised a prospective cohort study concerning breast cancer patients treated at a public oncology centre. A time interval of ≥60 days between surgery and the beginning of the first adjuvant treatment was categorised as a delay. Factors associated with delays were evaluated through logistic regression analysis and the prognosis effects were assessed by a Cox regression analysis. Results: The median time interval between surgery and the first adjuvant treatment for the 401 women included in this study was of 57.0 days (37.0–93.0). Independent factors associated with delays comprised not presenting an overexpression of the HER‐2 protein, not having undergone neoadjuvant chemotherapy, and having undergone chemotherapy or other therapeutic modalities other than hormone therapy and chemotherapy as the first adjuvant treatment. Delays did not affect recurrence, distant metastasis, or death risks. Factors associated with recurrence and distant metastasis risks comprised a clinical staging ≥2B, having undergone neoadjuvant chemotherapy, presenting the luminal molecular subtype B and triple‐negative tumours, and having children. Factors associated with death comprised triple‐negative molecular tumours and neoadjuvant chemotherapy. Conclusion: Delays in beginning adjuvant treatment did not affect the prognosis of non‐metastatic breast cancer patients. Clinical and treatment‐related factors, on the other hand, were associated with delays, and recurrence, distant metastasis, and death risks. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to conduct a detailed geospatial analysis of mobile phone signal coverage in the northwest macro-region of Paraná State, Brazil, seeking to identify areas where limitations in coverage may be related to lengthy travel times of the helicopter emergency medical service (HEMS) for the assistance of victims of road traffic injuries (RTIs). Methods: An observational study was conducted to examine mobile phone signal coverage and HEMS travel times from 2017 to 2021. HEMS travel times were categorized into four groups: T1 (0–15 min), T2 (16–30 min), T3 (31–45 min), and T4 (over 45 min). Empirical Bayesian Kriging was used to map areas with low mobile signal coverage. The Kruskal–Wallis test and Dwass–Steel–Critchlow–Fligner comparative analyses were performed to explore how mobile signal coverage relates to HEMS travel times to RTI locations. Results: There were 470 occurrences of RTIs attended by HEMS, of which 108 (23%) resulted in on-site fatalities. Among these deaths, 47 (26.85%) occurred in areas with low mobile phone signal coverage ("shadow areas"). Low mobile phone signal coverage identified at 175 (37.24%) RTIs locations, was unevenly distributed across the macro-region. The lowest medians of mobile signal quality were predominantly found in areas with HEMS travel times exceeding 30 min, corresponding to signal strength values of −98.44 (T3) and −100.75 (T4) dBm. This scenario represents a challenge for effective communication to activate HEMS. In the multiple comparison analysis among travel time groups, significant differences were observed between T1 and T2 (p < 0.001), T1 and T3 (p < 0.001), T1 and T4 (p < 0.001), and T2 and T3 (p < 0.001), indicating a potential association between lower mobile phone signal coverage and longer HEMS travel times. Conclusion: It can be concluded that poor mobile phone signals in remote areas can hinder HEMS activation, potentially delaying the start of treatment for RTIs. Identification of the shadow areas can help communication and health managers in designing and implementing the necessary changes to improve mobile phone signal coverage and consequently reduce delays in the initial response to RTIs. [ABSTRACT FROM AUTHOR]

Purpose: The time from breast cancer surgery to chemotherapy has been shown to affect survival outcomes; however, the effect of time from first breast cancer-related healthcare contact to first cancer specialist consultation, or the time from first breast cancer-related healthcare contact to adjuvant chemotherapy on survival has not been well explored. We aimed to determine whether various wait times along the breast cancer treatment pathway (contact-to-consultation, contact-to-chemotherapy, surgery-to-chemotherapy) were associated with overall survival in women within the Canadian province of Ontario. Methods: We performed a population-based retrospective cohort study of women diagnosed with stage I–III breast cancer in Ontario between 2007 and 2011 who received surgery and adjuvant chemotherapy. This was the Ontario cohort of a larger, nationwide study (the Canadian Team to improve Community-Based Cancer Care along the Continuum – CanIMPACT). We used Cox-proportional hazards regression to determine the association between the contact-to-consultation, contact-to-chemotherapy, and surgery-to-chemotherapy intervals and overall survival while adjusting for cancer stage, age, comorbidity, neighborhood income, immigration status, surgery type, and method of cancer detection. Results: Among 12,782 breast cancer patients, longer surgery-to-chemotherapy intervals (HR 1.13, 95% CI 1.03–1.18 per 30-day increase), but not the contact-to-consultation (HR 0.979, 95% CI 0.95–1.01 per 30-day increase), nor the more comprehensive contact-to-chemotherapy intervals (HR 1.00, 95% CI 0.98–1.02 per 30-day increase) were associated with decreased survival in our adjusted analyses. Conclusion: Our findings emphasize the prognostic importance of a shorter surgery-to-chemotherapy interval, whereas the contact-to-consultation and contact-to-chemotherapy intervals have less impact on survival outcomes. [ABSTRACT FROM AUTHOR]

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.

Nina Hein,1 Conner Callaway,2 Devin Ford,2 John C Carlson1 1Ochsner Health System, Department of Allergy and Clinical Immunology, New Orleans, LA, USA; 2Tulane University, School of Medicine, New Orleans, LA, USACorrespondence: John C Carlson, Department of Pediatrics, Ochsner Health System, 1315 Jefferson Hwy, New Orleans, LA, 20121, USA, Tel +1-504-842-3900, Fax +1-504-842-5848, Email john.carlson@ochsner.org

In order to explore the optimal time of endoscopy in patients with acute upper gastrointestinal hemorrhage (UGIB). 736 patients with acute UGIB who received digestive endoscopy examination in the Emergency Department of Beijing Friendship Hospital from June 2020 to June 2022 were retrospective analysised. According to the endoscopic examination time after visit the Department of Emergency, the patients were divided into emergency endoscopy group (within 12 hours after visit the Department of Emergency) and selective endoscopy group (after 12 hours). The general clinical data, endoscopic related data, interventional embolization rate, surgical procedure rate, blood transfusion volume, 30 day rebleeding rate, mortality rate, and average hospital stay of the two groups were compared. A total of 428 patients were enrolled in this study, 326 of whom underwent emergency endoscopic examination (76. 2%). Compared with the elective endoscopy group, the emergency endoscopy group showed a significant increase in heart rate (P =0. 043) and a decrease in systolic blood pressure (P =0. 061). 14 patients (3. 3%) were referred to the vascular intervention department for transarterial embolization after endoscopic treatment failed, while 6 patients (1. 4%) were transferred to general surgery for surgical treatment. The two groups of patients (P =0. 115,P =0. 561) showed no significant difference. There was no significant difference in average blood transfusion volume and hospital stay between the two groups of patients (P =0. 138,P =0. 799). The rate of rebleeding within 30 days was 10. 0% (43/428), 11. 7% (38/326) in the emergency endoscopy group, and 4. 9% (5/102) in the elective endoscopy group (P =0. 048). The total 30-day mortality rate was 6. 8% (29/428), and there was no difference between the emergency endoscopy group and the elective endoscopy group (7. 7% and 3. 9%,P =0. 189). Compared with emergency endoscopy, elective endoscopy for UGIB patients has a lower probability of rebleeding after 30 days, and there is no significant difference in intervention embolization rate, surgical surgery rate, blood transfusion volume, 30-day mortality rate, and average hospital stay. After hemodynamic stability, UGIB patients should use selective endoscopy. [ABSTRACT FROM AUTHOR]

AbstractPurpose This study investigates how the COVID-19 pandemic (CP) impacted the timeline between initial diagnosis (ID) of prostate carcinoma and subsequent therapy consultation (TC) or radical prostatectomy (RP) due to the implementation of a “minimal contact concept,” which postponed clinical examinations until the day of admission.Methods We analyzed patient data from a tertiary care center from 2018 to September 2021. The focus was on comparing the time intervals from ID to TC and from ID to RP before and during the CP.Results Of 12,255 patients, 6,073 (61.6%) were treated before and 3,791 (38.4%) during the CP. The median time from ID to TC reduced from 37 days (IQR: 21 – 58d) pre-CP to 32 days (IQR: 20 – 50d) during CP (p

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.

Introduction: Timely institution of pre-hospital therapies aimed at damage control and the appropriately timed decision of transfer to higher centers for definitive neurosurgical management are crucial in determining the outcome of patients following traumatic brain injury. This study aimed to evaluate the factors determining pre-hospital care and delay in patients with traumatic brain injury. Methods: This was a descriptive cross-sectional study conducted in a tertiary care center after obtaining ethical approval from the Institutional Review Board (approval number 392 (6-11) E2). All patients with traumatic brain injury who presented to the emergency department from 1 July, 2018 to 15 June, 2019 were enrolled. Data related to patient demographics, the primary cause of the incident, grading of traumatic brain injury on admission, pre-hospital care, and variables that cause pre-hospital delay were collected. Results: In this study of 144 patients with traumatic brain injury, we found that 70 (48.61%) experienced transfer delays exceeding one hour. There were 71 (49.31%) patients aged 15-44 years, and 100 (69.44%) were males , with falls being the primary cause of 119 (82.64%). Most patients had mild traumatic brain injury 80 (55.56%). Out of 144, 20 (13.89%) received prehospital care, and 28 (19.44%) underwent a computed tomography scan of the head before arrival. Conclusions: Our study highlights the challenges in pre-hospital care and delays in reaching for neurosurgical care in patients with traumatic brain injury. Falls, road accidents, and physical assaults were the leading causes.

Haemophilia is associated with a high tendency of acute bleeding episodes which can lead to severe morbidity and mortality in the absence of prompt care. Although delay in seeking care can lead to adverse outcomes, many people with haemophilia (PwH) in Uganda do not report to haemophilia treatment centres (HTCs) for treatment in the event of acute bleeding within the two hours recommended by the World Federation of Hemophilia (WFH). Information on factors associated with delays in seeking care is limited.

Objective. To determine if there was an association between intrapartum stillbirths and both traveled distance for delivery and delivery care accessibility, assessing periods before and during the COVID-19 pandemic. Methods. This is a population-based cohort study. Patients had birth occurring after the onset of labor; the primary outcome was intrapartum stillbirth. City of residence was classified according to the ratio between deliveries performed and total births among its residents; values lower than 0.1 indicated low delivery care accessibility. Travel distance was calculated using the Haversine formula. Education level, maternal age, and birth sex were included. In each period, relative risk was assessed by generalized linear model with Poisson variance. Results. There were 2 267 534 deliveries with birth occurring after the onset of labor. Most patients were between age 20 and 35 years, had between 8 and 11 years of education, and resided in cities with high delivery care accessibility. Low delivery care accessibility increased risk of intrapartum stillbirth in the pre-pandemic (relative risk [RR] 2.02; 95% CI [1.64, 2.47]; p < 0.01) and the pandemic period (RR 1.69; 95% CI [1.09, 2.55]; p = 0.015). This was independent of other risk-increasing factors, such as travel distance and fewer years of education. Conclusions. Low delivery care accessibility is associated with the risk of intrapartum stillbirths, and accessibility reduced during the pandemic. Delivery of patients by family physicians and midwives, as well as official communication channels between primary care physicians and specialists, could improve patient healthcare-seeking behavior.

Early detection plays a key role to enhance the outcome for Coronary Artery Disease. We utilized a big data analytics platform on ∼32,000 patients to trace patients from the first encounter to CAD treatment. There are significant gender-based differences in patients younger than 60 from the time of the first encounter to Coronary Artery Bypass Grafting with a p-value=0.03. This recognition makes significant changes in outcome by avoiding delay in treatment.

Carbon monoxide (CO) is one of the most common causes of intoxication. Delayed neurologic sequelae (DNS) have a major impact on prognosis of CO poisoning patients. Hyperbaric oxygen therapy (HBOT) is widely used to treat DNS. However, there is no consensus regarding the optimal timing of HBOT. This prospective study enrolled patients who visited the hospital from November 2019 to October 2022. The cutoff value for the latency to HBOT after CO exposure was determined, and the area under the receiver operating characteristic curve (AUC) was estimated. In total, 167 patients were divided into non-DNS and DNS groups. The initial Glasgow Coma Scale (GCS) score, CO exposure time, latency to HBOT after CO exposure, median length of hospital stay (p < 0.001) and creatine kinase (p = 0.016) showed significant differences. A GCS score ≤ 9 had an odds ratio (OR) of 5.059 (95% confidence interval [CI]: 1.602–15.976, p = 0.006), and latency to HBOT after CO exposure ≥ 200 min had an OR of 18.971 (95% CI: 4.310–83.508, p < 0.001). The AUC was 0.8235 (95% CI: 0.7504–0.8966). A GCS score ≤ 9 and latency to HBOT ≥ 200 min may be significant risk factors for DNS. [ABSTRACT FROM AUTHOR]

India has one of the highest burden of burns. The health systems response to burn care is sometimes patchy and highly influenced by social determinants. Delay in access to acute care and rehabilitation adversely affects recovery outcomes. Evidence on underlying factors for delays in care are limited. In this study, we aim to explore patients' journeys to analyse their experiences in accessing burn care in Uttar Pradesh, India. We conducted qualitative inquiry using the patient journey mapping approach and in-depth interviews (IDI). We purposively selected a referral burn centre in Uttar Pradesh, India and included a diverse group of patients. A chronological plot of the patient's journey was drawn and confirmed with respondents at the end of the interview. A detailed patient journey map was drawn for each patient based on interview transcripts and notes. Further analysis was done in NVivo 12 using a combination of inductive and deductive coding. Similar codes were categorised into sub-themes, which were distributed to one of the major themes of the 'three delays' framework. Six major burns patients (4 female and 2 males) aged between 2 and 43 years were included in the study. Two patients had flame burns, and one had chemical, electric, hot liquid, and blast injury, respectively. Delay in seeking care (delay 1) was less common for acute care but was a concern for rehabilitation. Accessibility and availability of services, costs of care and lack of financial support influenced delay (1) for rehabilitation. Delay in reaching an appropriate facility (delay 2) was common due to multiple referrals before reaching an appropriate burn facility. Lack of clarity on referral systems and proper triaging influenced this delay. Delay in getting adequate care (delay 3) was mainly due to inadequate infrastructure at various levels of health facilities, shortage of skilled health providers, and high costs of care. COVID-19-related protocols and restrictions influenced all three delays. Burn care pathways are adversely affected by barriers to timely access. We propose using the modified 3-delays framework to analyse delays in burns care. There is a need to strengthen referral linkage systems, ensure financial risk protection, and integrate burn care at all levels of health care delivery systems. • The first study from a low-and middle-income country exploring patients' journeys and 'three delays' in burns care. • Findings suggest long delays in reaching an appropriate health facility and receiving adequate care. • The absence referral linkage between facilities and high treatement cost, are identified are critical barriers to timely care. • We propose a modified 'three-delays' framework to analyse factors causing delays in accessing burn care. [ABSTRACT FROM AUTHOR]

To investigate the association between the Emergency Medical Service dispatcher's initial stroke triage and prehospital stroke management, primary admission to hospitals offering revascularization treatment, prehospital time delay, and rate of acute revascularization. In an observational cohort study, patients with acute ischemic stroke (AIS) in Denmark (2017–2018) were included if the emergency call to the Emergency Medical Dispatch Center (EMDC) was made within three hours after symptom onset. Among 3546 included AIS patients, the EMS dispatcher identified 74.6% (95% confidence interval (CI) 73.1–76.0) correctly as stroke. EMS dispatcher stroke recognition was associated with a higher rate of primary admission to a hospital offering revascularization treatment (85.8 versus 74.5%); producing an adjusted risk difference (RD) of 11.1% (95% CI 7.8; 14.3) and a higher rate of revascularization treatment (49.6 versus 41.6%) with an adjusted RD of 8.4% (95% CI 4.6; 12.2). We adjusted for sex, age, previous stroke or transient ischemic attack, and stroke severity. EMDC stroke recognition was associated with shorter prehospital delay. For all AIS patients, the adjusted difference was − 33.2 min (95% CI − 44.4; − 22.0). Among patients receiving acute revascularization treatment (n = 1687), the adjusted difference was -12.6 min (95% CI − 18.9; − 6.3). Stroke recognition by the EMS dispatcher was associated with a higher probability of primary admission to a hospital offering acute stroke treatment, and subsequently with a higher rate of acute revascularization treatment, and with an overall reduction in prehospital delay. [ABSTRACT FROM AUTHOR]

Introduction: There is no consensus in the literature on a reasonable delay time from diagnosis to radical prostatectomy (RP) surgery, without worsening the prognosis. Objective: To evaluate the influence of the delay on the risk of disease recurrence in patients with acinar adenocarcinoma of the prostate treated with RP. Method: Four hundred and twelve patients undergoing RP were retrospectively evaluated. Of these, 172 were excluded due to incomplete data and another 28 due to preoperative staging as high-risk prostate cancer (PSA > 10 ng/mL or Gleason score on biopsy > 7). Pre-and postoperative stagings were compared and survival analysis was performed using the Kaplan-Meier method to investigate the influence of time on discordance between pre- and postoperative stagings. Results: For the 212 patients of the sample, the average time from diagnosis to RP was 176.1 ± 120.2 days (median 145.5 days), ranging from 29 to a maximum of 798 days. The Kaplan-Meier curve indicated that the cancer worsened the longer the delay between diagnosis and surgery. Patients undergoing surgery within 60 days had an approximately 95% probability of not increasing the initial risk of recurrence. This number fell to 80%, 70% and 50% in patients operated on up to 100, 120 and 180 days, respectively. Conclusion: Delay in performing RP represents a continuous risk of relapse. The ideal time for RP is up to 60 days from prostate biopsy, as the probability of upstaging is less than 5% in this period.

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 (

Objective:It was aimed to investigate the effect of early diuretic treatment on hospitalization and short-term mortality in patients with acute heart failure.Method:Our study was carried out as a retrospective, single-centered, observational study in the department of emergency a tertiary training and research hospital. The study population was the patients presenting with signs and symptoms of acute heart failure. The primary outcome was all-cause 30-day mortality and hospitalization. Univariant tests and ROC analysis were used for analysis.Results:A total of 325 patients were included. The median age of the patients was 76.0 years (interquartile range 69.0-83.0). The mortality rate of our study population was %14.4 (47). Systolic blood pressure and diastolic blood pressure were significantly higher in the survivor group (p=0.018, 0.033, respectively). Age, troponin-I, and pro-brain natriuretic peptide were significantly higher in the non-survivor group (p

Abstract Background Clozapine is the only antipsychotic medication with proven efficacy against treatment-resistant schizophrenia. This multicenter retrospective cohort study aimed to evaluate the impact of a delay in clozapine initiation on long-term outcomes. Methods Patients who initiated clozapine treatment between July 2009 and December 2018 were included in this study. According to the length of time from the diagnosis of schizophrenia to clozapine initiation, the patients were categorized into one of three groups: early (≤ 9 years), intermediate (10–19 years), and late (≥ 20 years) initiation. The endpoints were psychiatric rehospitalization and all-cause clozapine discontinuation within 3 years. Hazard ratios (HR) and 95% confidence interval (CI) were estimated using the Fine and Gray method or the Cox proportional hazards model. Results The incidence rates of rehospitalization within three years, according to the cumulative incidence function, were 32.3% for early, 29.7% for intermediate, and 62.2% for late initiation, respectively. Late initiation had a significantly higher risk of psychiatric rehospitalization than early initiation (HR, 2.94; 95% CI, 1.01– 8.55; P = 0.016 by the Gray's test). The risk of psychiatric rehospitalization was not significantly different between the early and intermediate initiation groups. The incidence rate of all-cause clozapine discontinuation within three years using the Kaplan–Meier method was 13.0% for early, 10.6% for intermediate, and 20.1% for late initiation. The risk of all-cause clozapine discontinuation was not significantly among the groups. The late initiation group had more patients discontinuing because of death due to physical diseases than the other groups. Conclusions The study suggests that clozapine should be initiated promptly in patients with treatment-resistant schizophrenia to prevent psychiatric rehospitalization during long-term treatment. Further prospective studies with appropriate consideration of confounding factors and large sample sizes are needed to strengthen the evidence.

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.

BackgroundOne in five patients diagnosed with TB in Uganda are not initiated on TB treatment within two weeks of diagnosis. We evaluated a multifaceted intervention for improving TB treatment initiation among patients diagnosed with TB using Xpert® MTB/RIF testing in Uganda.MethodsThis was a pre-post interventional study at one tertiary referral hospital. The intervention was informed by the COM-B model and included; i) medical education sessions to improve healthcare worker knowledge about the magnitude and consequences of pretreatment loss to follow-up; ii) modified laboratory request forms to improve recording of patient contact information; and iii) re-designed workflow processes to improve timeliness of sputum testing and results dissemination. TB diagnostic process and outcome data were collected and compared from the period before (June to August 2019) and after (October to December 2019) intervention initiation.ResultsIn September 2019, four CME sessions were held at the hospital and were attended by 58 healthcare workers. During the study period, 1242 patients were evaluated by Xpert® MTB/RIF testing at the hospital (679 pre and 557 post intervention). Median turnaround time for sputum test results improved from 12 hours (IQR 4-46) in the pre-intervention period to 4 hours (IQR 3-6) in the post-intervention period. The proportion of patients started on treatment within two weeks of diagnosis improved from 59% (40/68) to 89% (49/55) (difference 30%, 95% CI 14%-43%, p

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.).

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has disrupted breast cancer control through short-term declines in screening and delays in diagnosis and treatments. We projected the impact of COVID-19 on future breast cancer mortality between 2020 and 2030.MethodsThree established Cancer Intervention and Surveillance Modeling Network breast cancer models modeled reductions in mammography screening use, delays in symptomatic cancer diagnosis, and reduced use of chemotherapy for women with early-stage disease for the first 6 months of the pandemic with return to prepandemic patterns after that time. Sensitivity analyses were performed to determine the effect of key model parameters, including the duration of the pandemic impact.ResultsBy 2030, the models project 950 (model range = 860-1297) cumulative excess breast cancer deaths related to reduced screening, 1314 (model range = 266-1325) associated with delayed diagnosis of symptomatic cases, and 151 (model range = 146-207) associated with reduced chemotherapy use in women with hormone positive, early-stage cancer. Jointly, 2487 (model range = 1713-2575) excess breast cancer deaths were estimated, representing a 0.52% (model range = 0.36%-0.56%) cumulative increase over breast cancer deaths expected by 2030 in the absence of the pandemic's disruptions. Sensitivity analyses indicated that the breast cancer mortality impact would be approximately double if the modeled pandemic effects on screening, symptomatic diagnosis, and chemotherapy extended for 12 months.ConclusionsInitial pandemic-related disruptions in breast cancer care will have a small long-term cumulative impact on breast cancer mortality. Continued efforts to ensure prompt return to screening and minimize delays in evaluation of symptomatic women can largely mitigate the effects of the initial pandemic-associated disruptions.

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

This document summarizes suggestions of the central sleep apnea (CSA) Technical Expert Panel working group. This paper shares our vision for bringing the right device to the right patient at the right time. For patients with CSA, current coverage criteria do not align with guideline treatment recommendations. For example, CPAP and oxygen therapy are recommended but not covered for CSA. On the other hand, bilevel positive airway pressure (BPAP) without a backup rate may be a covered therapy for OSA, but it may worsen CSA. Narrow coverage criteria that require near elimination of obstructive breathing events on CPAP or BPAP in the spontaneous mode, even if at poorly tolerated pressure levels, may preclude therapy with BPAP with backup rate or adaptive servoventilation, even when those devices provide demonstrably better therapy. CSA is a dynamic disorder that may require different treatments over time, sometimes switching from one device to another; an example is switching from BPAP with backup rate to an adaptive servoventilation with automatic end-expiratory pressure adjustments, which may not be covered. To address these challenges, we suggest several changes to the coverage determinations, including: (1) a single simplified initial and continuing coverage definition of CSA that aligns with OSA; (2) removal of hypoventilation terminology from coverage criteria for CSA; (3) all effective therapies for CSA should be covered, including oxygen and all PAP devices with or without backup rates or servo-mechanisms; and (4) patients shown to have a suboptimal response to one PAP device should be allowed to add oxygen or change to another PAP device with different capabilities if shown to be effective with testing.

The 2012 Berlin definition of acute respiratory distress syndrome (ARDS) provided validated support for three levels of initial arterial hypoxaemia that correlated with mortality in patients receiving ventilatory support. Since 2015, high-flow nasal oxygen (HFNO) has become widely used as an effective therapeutic support for acute respiratory failure, most recently in patients with severe COVID-19. We propose that the Berlin definition of ARDS be broadened to include patients treated with HFNO of at least 30 L/min who fulfil the other criteria for the Berlin definition of ARDS. An expanded definition would make the diagnosis of ARDS more widely applicable, allowing patients at an earlier stage of the syndrome to be recognised, independent of the need for endotracheal intubation or positive-pressure ventilation, with benefits for the testing of early interventions and the study of factors associated with the course of ARDS. We identify key questions that could be addressed in refining an expanded definition of ARDS, the implementation of which could lead to improvements in clinical practice and clinical outcomes for patients.

Corey L Snyder,1,2 Stella X Chen,1,3 Martina L Porter1,4 1Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA; 2Department of Dermatology, University of Texas Southwestern Medical School, Dallas, TX, USA; 3Department of Dermatology, Massachusetts General Hospital, Harvard Combined Dermatology Residency Program, Boston, MA, USA; 4Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USACorrespondence: Martina L Porter, Department of Dermatology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Dermatology Research GZ 522, Boston, MA, 02215, USA, Tel +1-617-667-5834, Fax +1-617-667-4980, Email mporter3@bidmc.harvard.eduAbstract: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can progress to significant tunnels and scars that affect quality of life, especially if diagnosis and treatment are delayed. Average delay after initial presentation of HS symptoms can range from 3 to 10 years in adults and 1 to 2 years in children. Factors associated with diagnostic delay include female gender, non-white race, and greater disease severity at diagnosis. Contributing factors include misdiagnoses, difficulty accessing a dermatologist, hesitation in seeking care due to the stigmatizing nature of the disease, and lack of awareness among providers and patients. While efforts to increase awareness include academic talks at conferences and by foundations geared toward HS, social media offers the opportunity to reach young audiences. Many patients report dissatisfaction with their HS treatments. Better understanding of HS pathophysiology and implementation of clinically focused phenotypes and endotypes can lead to development of more targeted and efficacious therapies. FDA approval of medications for HS beyond adalimumab will increase access to a wider selection of therapies, and implementation of therapeutic drug monitoring may maximize the use of biologics for HS.Keywords: hidradenitis suppurativa, acne inversa, diagnosis, delayed diagnosis, therapeutics, time-to-treatment

Abstract Background Cutaneous Leishmaniasis (CL) affects up to 5.000 people in Ecuador each year. L. guyanensis and L. braziliensis are the most common of the eight CL-causing Leishmania species. Earlier CL research concentrated on the easily accessible Pacific region. This study aims to describe the Leishmania species in Pacific and Amazon ecoregions, to analyze regional differences in CL patient clinical presentation, and to identify determinants of health-seeking delay. Methods All cases in this cross-sectional study were diagnosed using smear slide microscopy, PCR, or both. Cytochrome B gene sequencing was used to identify the causative Leishmania species in qPCR-positive samples. Results This study included 245 patients, with 154 (63%) infected in the Pacific region and 91 (37%) infected in the Amazon. Causative Leishmania species were identified in 135 patients (73% of qPCR positives). L. guyanensis was identified in 76% (102/135) of the samples and L. braziliensis in 19% (26/135). The Pacific region had a low prevalence of 6% (5/89) of L. braziliensis. For the first time, we report L. guyanensis from the central Amazon, L. braziliensis from the northern Pacific, and L. lainsoni from both the central Amazon and northern Pacific. Amazon cases had a longer median health-seeking delay in months (2.0, IQR 3.0) than Pacific cases (1.0, IQR 1.5). Prolonged health-seeking delay was associated with older age, Amerindian ethnicity, infection at lower altitudes, non-ulcerative lesions, and lesions on the lower limbs. Conclusions In the Pacific region, health-seeking delay is relatively short and L. braziliensis prevalence remains low. Limited access to health care and stigma might explain the prolonged health-seeking delay in the Amazon. We recommend larger studies on the distribution of Leishmania species in Amazon CL cases and additional regional research into diagnostic test accuracy. Furthermore, the determinants of health-seeking delay in Ecuador should be investigated further.

Objective: Although surgical treatment of hip fracture provides favourable outcomes, comorbidities and preoperative optimization determine the recovery and rehabilitation period in elderly population. This study evaluated the role of anesthesiologic management for appropriate timing of surgery, and other patient-specific factors for surgical intervention. Methods: The study group comprised of 240 geriatric patients with acute hip fractures, who underwent surgery at an academic tertiary care unit. Preoperative, intraoperative and postoperative variables associated with anesthesiologic management were retrospectively evaluated. A 30-day mortality and morbidity were the primary and secondary outcomes. Results: The median time between the patient’s admission to the hospital and the time of surgery was 1 day. Approximately 29% patients stayed in intensive care unit postoperatively. The median length of hospitalization was 5 days, while the 30-day mortality rate was 1.3%. The American Society of Anesthesiologists (ASA) physical status was identified as the most common factor that significantly affected the 30-day mortality. Conclusion: To date, no consensus has been reached on the appropriate delay period for surgery of acute hip fractures. Our study demonstrates that the main factors determining the patient prognosis are ASA physical status score, and the functional status of the patients. Therefore, perioperative anesthesiologic management should be prioritized to provide optimization of these patients. [ABSTRACT FROM AUTHOR]

Background: Timeliness in the management of patients with head and neck cancer (HNC) can be affected by both patient and non‐patient related factors. This study aims to investigate the factors associated with the timeliness of managing HNC. Methods: A retrospective review was conducted on Western Health medical records including all new patients presenting to the Western Health HNC surgical outpatient clinic in the five‐year period from first January 2017 to 31st December 2021 with the diagnosis of a HNC. Both patient and non‐patient related factors were compared with the duration between a patient's referral to a HNC service and the commencement of their treatment. Results: Two hundred and twenty‐eight patients were included in this study. The median duration from referral to the commencement of treatment was 48 days. Lack of radiological or pathological investigations prior to referral to a HNC service as well as early staging were found to significantly impact timeliness in management. Socioeconomic factors such as non‐English speaking backgrounds, distance from the hospital and lack of social supports were not found to negatively impact timeliness of management. Conclusion: The management of patients with HNC require careful consideration of all patient and non‐patient related factors which may affect timeliness in management, particularly investigations performed prior to their referral to a HNC service. A retrospective review was conducted on Western Health medical records including all new patients presenting to the Western Health HNC surgical outpatient clinic in the five‐year period from 1st January 2017 to 31st December 2021 with the diagnosis of a HNC. Lack of radiological or pathological investigations prior to referral to a HNC service, referrals from general practitioners, as well as early staging were found to be associated with significantly greater delays in management. The management of patients with HNC require careful consideration of all patient and non‐patient related factors which may result in management delays, particularly investigations performed prior to their referral to a HNC service. [ABSTRACT FROM AUTHOR]

Background: Short period from diagnosis to breast cancer (BC) treatment initiation remains challenging for the public health system in Brazil, which may have been further affected by the coronavirus disease-2019 (COVID-19) pandemic. This study assessed BC diagnosis-to-treatment intervals (DTi) in Brazil and the possible effects of the COVID-19 outbreak on delays. Methods: The Painel de Monitoramento de Tratamento Oncológico database was queried to obtain the number of Brazilian patients with a BC confirmed diagnosis and initiating cancer treatment in the pre-COVID-19 (2013-2019) and during the COVID-19 (2020-2021) periods, adopting a 60-day limit as timely treatment. A p-value of <0.05 was considered significant. Results: A total of 315,951 cases were included (females: 99.3% and males: 0.7%), of which 251,667 and 64,284 records were computed before and during the COVID-19 years, respectively. Most patients failed to perform the first cancer treatment within 60 days (>60: 51.8%). We observed an upward trend in the number of BC treatments provided in the pre-COVID-19 years (r² = 0.9575; p < 0.05), but the volume of treatments exhibited an average reduction of 24.6% yearly during the COVID-19 pandemic. The average DTi in days was 122.4, 122.5 and 122.3 in the total period studied, before and during the COVID-19 outbreak, respectively. The arrival of COVID-19 in Brazil increased the chances of treatment delay (OR = 1.043; p < 0.05) and inverted the proportion of early/advanced stages at BC diagnosis (55.8%/44.2%-48.4%/51.6%). Conclusion: COVID-19 has imposed changes in BC care in Brazil, reducing the number of treatments provided by the Brazilian public health system, increasing the chances of delayed treatment initiation despite no differences in DTi averages being identified, and raising the proportion of advanced-stage diagnoses. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to report the safety and performance of aspiration thrombectomy with the Penumbra System for patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO) and late onset to treatment. Methods: This is a retrospective subset analysis of a global prospective multicenter registry (COMPLETE) that enrolled adults with AIS due to LVO and a pre-stroke modified Rankin Scale score (mRS) of 0 or 1 who were treated first-line with aspiration thrombectomy either alone (A Direct Aspiration First Pass Technique [ADAPT]) or in combination with the 3D Revascularization Device (ADAPT + 3D). This subset analysis included all patients in the registry who had anterior circulation LVO, an Alberta Stroke Program Early CT Score of at least 6, and late onset to treatment (>6 h from stroke onset to puncture). Results: Of the 650 patients in the COMPLETE registry, 167 were included in this subset analysis. The rate of successful revascularization (modified thrombolysis in cerebral infarction score 2b-3 achieved) at the end of the procedure was 83.2%, the rate of good functional outcome (mRS 0-2) at 90 days was 55.4%, and the all-cause mortality rate at 90 days was 14.4%. No device-related serious adverse events (SAEs) occurred. Procedure-related SAEs occurred in 9 patients (5.4%) within 24 h and in 12 patients (7.2%) overall. The rate of successful revascularization was higher for patients treated first-line with ADAPT (88.0%) than for patients treated first-line with ADAPT + 3D (75.0%; p = 0.035); no significant difference was observed between the ADAPT and ADAPT + 3D groups for any other primary or secondary outcome. Conclusion: For patients with AIS due to anterior circulation LVO and with late onset to treatment, aspiration thrombectomy with the Penumbra System appears to be safe and effective. The rates of good functional outcome and all-cause mortality from this study compared favorably with those rates from the medical management arms of the DAWN and DEFUSE-3 studies. [ABSTRACT FROM AUTHOR]

Background: Clozapine is the only antipsychotic medication with proven efficacy against treatment-resistant schizophrenia. This multicenter retrospective cohort study aimed to evaluate the impact of a delay in clozapine initiation on long-term outcomes. Methods: Patients who initiated clozapine treatment between July 2009 and December 2018 were included in this study. According to the length of time from the diagnosis of schizophrenia to clozapine initiation, the patients were categorized into one of three groups: early (≤ 9 years), intermediate (10–19 years), and late (≥ 20 years) initiation. The endpoints were psychiatric rehospitalization and all-cause clozapine discontinuation within 3 years. Hazard ratios (HR) and 95% confidence interval (CI) were estimated using the Fine and Gray method or the Cox proportional hazards model. Results: The incidence rates of rehospitalization within three years, according to the cumulative incidence function, were 32.3% for early, 29.7% for intermediate, and 62.2% for late initiation, respectively. Late initiation had a significantly higher risk of psychiatric rehospitalization than early initiation (HR, 2.94; 95% CI, 1.01– 8.55; P = 0.016 by the Gray's test). The risk of psychiatric rehospitalization was not significantly different between the early and intermediate initiation groups. The incidence rate of all-cause clozapine discontinuation within three years using the Kaplan–Meier method was 13.0% for early, 10.6% for intermediate, and 20.1% for late initiation. The risk of all-cause clozapine discontinuation was not significantly among the groups. The late initiation group had more patients discontinuing because of death due to physical diseases than the other groups. Conclusions: The study suggests that clozapine should be initiated promptly in patients with treatment-resistant schizophrenia to prevent psychiatric rehospitalization during long-term treatment. Further prospective studies with appropriate consideration of confounding factors and large sample sizes are needed to strengthen the evidence. [ABSTRACT FROM AUTHOR]

The purpose of our study was to analyze the impact of time interval from referral to surgery and from surgery to adjuvant treatment on survival of adult isocitrate dehydrogenase–wild-type (IDH-wt) glioblastomas. Data on 392 IDH-wt glioblastomas diagnosed at the Tampere University Hospital in 2004–2016 were obtained from the electronic patient record system. Piecewise Cox regression was used to calculate hazard ratios for different time intervals between referral and surgery, as well as between surgery and adjuvant treatments. The median survival time from primary surgery was 9.5 months (interquartile range: 3.8–16.0). Survival among patients with an interval exceeding 4 weeks from referral to surgery was no worse compared to <2 weeks (hazard ratio: 0.78, 95% confidence interval: 0.54–1.14). We found indications of poorer outcome when the interval from surgery to radiotherapy exceeded 30 days (hazard ratio: 1.42, 95% confidence interval: 0.91–2.21 for 31–44 days; and 1.59, 0.94–2.67 for over 45 days). Interval from referral to surgery in the range of 4–10 weeks was not associated with decreased survivals in IDH-wt glioblastomas. In contrast, delay exceeding 30 days from surgery to adjuvant treatment may decrease long-term survival. [ABSTRACT FROM AUTHOR]

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Rationale: Although the mainstay of sepsis treatment is timely initiation of broad-spectrum antimicrobials, treatment delays are common, especially among patients who develop hospital-onset sepsis. The time of day has been associated with suboptimal clinical care in several contexts, but its association with treatment initiation among patients with hospital-onset sepsis is unknown. Objectives: Assess the association of time of day with antimicrobial initiation among ward patients with hospital-onset sepsis. Methods: This retrospective cohort study included ward patients who developed hospital-onset sepsis while admitted to five acute care hospitals in a single health system from July 2017 through December 2019. Hospital-onset sepsis was defined by the Centers for Disease Control and Prevention Adult Sepsis Event criteria. We estimated the association between the hour of day and antimicrobial initiation among patients with hospital-onset sepsis using a discrete-time time-to-event model, accounting for time elapsed from sepsis onset. In a secondary analysis, we fit a quantile regression model to estimate the association between the hour of day of sepsis onset and time to antimicrobial initiation. Results: Among 1,672 patients with hospital-onset sepsis, the probability of antimicrobial initiation at any given hour varied nearly fivefold throughout the day, ranging from 3.0% (95% confidence interval [CI], 1.8--4.1%) at 7 A.M. to 13.9% (95% CI, 11.3--16.5%) at 6 P.M., with nadirs at 7 A.M. and 7 P.M. and progressive decline throughout the night shift (13.4% [95% CI, 10.7--16.0%] at 9 P.M. to 3.2% [95% CI, 2.0--4.0] at 6 A.M.). The standardized predicted median time to antimicrobial initiation was 3.2 hours (interquartile range [IQR], 2.5--3.8 h) for sepsis onset during the day shift (7 A.M.--7 P.M.) and 12.9 hours (IQR, 10.9--14.9 h) during the night shift (7 P.M.--7 A.M.). Conclusions: The probability of antimicrobial initiation among patients with new hospital-onset sepsis declined at shift changes and overnight. Time to antimicrobial initiation for patients with sepsis onset overnight was four times longer than for patients with onset during the day. These findings indicate that time of day is associated with important care processes for ward patients with hospital-onset sepsis. Future work should validate these findings in other settings and elucidate underlying mechanisms to inform quality-enhancing interventions. [ABSTRACT FROM AUTHOR]

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.

Abstract Background Given the dearth of data regarding the time to treatment initiation (TTI) in the palliative setting, and its impact on survival outcomes, we sought to determine TTI in a real‐world cohort of metastatic colorectal cancer (mCRC) and metastatic pancreatic cancer (mPC) patients and evaluate the impact of TTI on real‐world survival outcomes. Methods We collected survival and treatment data for mCRC and mPC from the Flatiron Health electronic health records (EHR) derived database. We divided TTI into 3 categories:

Over the past decade, 2 strategies have advanced the treatment of patients with multiple myeloma and its precursor diseases. First, the definition has changed to include patients without end organ damage, who previously would not have been treated. Second, there is widespread enthusiasm for treating high-risk, smoldering multiple myeloma. In this commentary, we explore the evidence supporting these therapeutic expansions. Although early treatment adds cost and therapeutic burden, it remains unknown whether survival and health-related quality of life are improved by early treatment. Herein, we consider the implications of diagnostic expansion in multiple myeloma.

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.