Novel Methodology for Linking 9-1-1 Dispatch Categories with a Death Registry: Mortality Rates of Selected Dispatch Categories.

OBJECTIVES: Medical Priority Dispatch System (MPDS) is a system used to assign medical 9-1-1 calls to one of 35 chief complaints that are further categorized in order of increasing priority, Alpha through Echo. In this descriptive study we demonstrate the methodology of matching MPDS codes to a county mortality registry. We also evaluated the ability of select MPDS codes (fall, respiratory, sick person, and abdominal pain) to predict mortality up to 30 d for all ages transported by Alameda County Emergency Medical Services (EMS). METHODS: Using Alameda County EMS data, we conducted a retrospective review of all EMS encounters that occurred from November 1, 2011, to November 1, 2016. To describe mortality in this population, we identified unique patients and linked them to the Alameda County Public Health Death Registry. We identified mortality at 48 h, 7 d, and 30 d after an EMS encounter. RESULTS: Approximately 99% of the EMS encounters were matched with unique patient identifiers, yielding a study sample of 202,431 (4% less than age 18, 53% between ages 18-65, and 43% over age 65). Patients with a respiratory chief complaint had the highest mortality percentage in each age group (0.23%, 2.7%, and 14.55% respectively). There was no correlation between the MPDS code and mortality for patients less than age 18. An increase in Alpha through Echo designation for respiratory complaints in patients 18-65 and older than 65 years corresponded with an increase in 30-day mortality. CONCLUSIONS: This study demonstrates an upward trend in mortality with increasing acuity of Alpha through Echo designations for adult patients with respiratory complaints. Mortality increased with age in this cohort. Most of the deaths occurred after 7 days.

A population study of respiratory rehospitalisation in very preterm infants in the first 3 years of life.

AIM: Very premature infants consume healthcare resources following discharge from neonatal intensive care units (NICU). This study aimed to evaluate the burden of respiratory related rehospitalisation within the first 3 years post discharge in very premature infants in an Australian population. METHODS: Rehospitalisation of a 4-year cohort of NICU survivors, born less than 32 weeks gestation, was derived from data linkage of three state-wide databases including NSW Neonatal Intensive Care Units' Data Collection, Admitted Patient Data Collection and the Death Registry. Rehospitalisation diagnoses were determined by ICD-10 AM codes. RESULTS: Of the 2939 survivors, 525 (18%) had bronchopulmonary dysplasia (BPD) and 261 BPD infants (50%) were discharged on home oxygen. Almost two-third (1860, 63%) of the survivors are required rehospitalisation, respiratory causes, including 394 respiratory syncytial virus (RSV)-related, accounted for 2668 (48%) of the 5599 rehospitalisations. Significantly more home oxygen BPD survivors had respiratory (70%) and RSV-related (22%) rehospitalisations than the BPD infants not needing home oxygen (58% and 18%, respectively), and the survivors without BPD had the lowest rates (32% and 10%, P < 0.001). Most respiratory (61%) and RSV-related (74%) rehospitalisations occurred during the first 12 months post discharge. No RSV-related fatality occurred. Amongst the total 17 562 hospital days, respiratory and RSV-related admissions accounted for 10 905 (62%) and 3031 (17.2%) days. In multivariable logistic analyses, home oxygen and maternal indigenous status were independently associated with high (3 or more) respiratory and RSV rehospitalisation rates. CONCLUSIONS: Respiratory rehospitalisations are common in very premature survivors. Home oxygen and indigenous status are significant risk factors for respiratory and RSV-related rehospitalisations.

Redefining Clinical Hyperprogression: The Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival. METHODS: Clinical and radiologic data from 121 non-small cell lung cancer (NSCLC) patients with 136 immunotherapy cases were reviewed retrospectively. Three HPD definitions (Champiat et al., HPDc; Saâda-Bouzid et al., HPDs; and Ferrara et al., HPDf) were employed. Additionally, all new measurable lesions on the post-treatment CT scan were incorporated in measuring the sum of longest diameters (SLD) to define modified HPD (mHPD). RESULTS: Among the 121 patients, 4 (3.3%) had HPDc, 11 (9.1%) had HPDs, and none had HPDf. Adding all new measurable lesions increased HPD incidence by 5%-10% across definitions. Multivariate analysis revealed significantly lower progression-free survival (PFS) and overall survival (OS) for patients with HPDc (HR 5.25, P = .001; HR 3.75, P = .015) and HPDs (HR 3.74, P < .001; HR 3.46, P < .001) compared to those without. Patients with mHPD showed similarly poor survival outcomes as HPD patients. Liver metastasis at diagnosis was associated with HPDs, and a high tumor burden correlated with HPDc. CONCLUSIONS: The incidence and risk factors of HPD varied with different definitions, but mHPD identified more cases with poor outcomes. This comprehensive approach may enhance the identification of at-risk patients and lead to a better understanding of HPD in lung cancer during immunotherapy.

Personalized, tumor-informed, circulating tumor DNA assay for detecting minimal residual disease in non-small cell lung cancer patients receiving curative treatments.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA-based MRD detection to predict recurrence in a real-world cohort of primarily early-stage non-small cell lung cancer (NSCLC) patients treated with curative intent. METHODS: Longitudinal plasma samples were collected post curative-intent treatment from 36 patients with stage I-IV NSCLC. A personalized, tumor-informed assay was used to detect and quantify ctDNA in plasma samples. RESULTS: Of the 24 patients with plasma samples available during the MRD window (within 6 months of curative surgery and before adjuvant therapy), ctDNA was detectable in two patients. Patients with ctDNA-positivity during the MRD window were 15 times more likely to recur compared to ctDNA-negative patients (HR: 15.0, 95% CI: 1.0-253.0, p = 0.010). At any time post-curative intent treatment, ctDNA-positivity was associated with significantly poorer recurrence-free survival compared to persistently ctDNA-negative patients (p < 0.0001). CONCLUSION: Our real-world data indicate that longitudinal, personalized, tumor-informed ctDNA monitoring is a valuable tool in patients with NSCLC receiving curative treatment to identify patients at high risk for recurrence.

Screening programmes for developmental dysplasia of the hip in newborn infants.

BACKGROUND: Uncorrected developmental dysplasia of the hip (DDH) is associated with long term morbidity such as gait abnormalities, chronic pain and degenerative arthritis. OBJECTIVES: To determine the effect of different screening programmes for DDH on the incidence of late presentation of congenital hip dislocation. SEARCH STRATEGY: Searches were performed in CENTRAL (The Cochrane Library), MEDLINE and EMBASE (January 2011) supplemented by searches of clinical trial registries, conference proceedings, cross references and contacting expert informants. SELECTION CRITERIA: Randomised, quasi-randomised or cluster trials comparing the effectiveness of screening programmes for DDH. DATA COLLECTION AND ANALYSIS: Three independent review authors assessed study eligibility and quality, and extracted data. MAIN RESULTS: No study examined the effect of screening (clinical and/or ultrasound) and early treatment versus not screening and later treatment.One study reported universal ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery but was associated with a significant increase in treatment.One study reported targeted ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery, with no significant difference in rate of treatment.Meta-analysis of two studies found universal ultrasound compared to targeted ultrasound did not result in a significant reduction in late diagnosed DDH or surgery. There was heterogeneity between studies reporting the effect on treatment rate.Meta-analysis of two studies found delayed ultrasound and targeted splinting compared to immediate splinting of infants with unstable (but not dislocated) hips resulted in no significant difference in the rate of late diagnosed DDH. Both studies reported a significant reduction in treatment with use of delayed ultrasound and targeted splinting.One study reported delayed ultrasound and targeted splinting compared to immediate splinting of infants with mild hip dysplasia on ultrasound resulted in no significant difference in late diagnosed DDH but a significant reduction in treatment. No infants in either group received surgery. AUTHORS' CONCLUSIONS: There is insufficient evidence to give clear recommendations for practice. There is inconsistent evidence that universal ultrasound results in a significant increase in treatment compared to the use of targeted ultrasound or clinical examination alone. Neither of the ultrasound strategies have been demonstrated to improve clinical outcomes including late diagnosed DDH and surgery. The studies are substantially underpowered to detect significant differences in the uncommon event of late detected DDH or surgery. For infants with unstable hips or mildly dysplastic hips, use of delayed ultrasound and targeted splinting reduces treatment without significantly increasing the rate of late diagnosed DDH or surgery.

A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon.

PURPOSE: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase, allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU combined with preoperative radiotherapy and determined the recommended Phase II dose and dose-limiting toxicity in patients with locally advanced rectal and colon cancer. METHODS AND MATERIALS: Patients with TNM Stage II or III rectal cancer and residual or recurrent colon cancer received eniluracil (starting at 6.0 mg/m(2) every 12 h) and 5-FU (starting at 0.6 mg/m(2) every 12 h). Eniluracil and 5-FU were given with a 5-week course of preoperative radiotherapy of 4500 cGy, with a possible 540-cGy boost. Surgery was performed approximately 4 weeks after completion of chemoradiotherapy. RESULTS: Twenty-two patients were enrolled; 1 patient was withdrawn owing to noncompliance. Chemotherapy was completed in all patients; radiotherapy was completed in 20 patients. The recommended Phase II dose of eniluracil and 5-FU was 8 mg/m(2) every 12 h and 0.8 mg/m(2) every 12 h, respectively. Diarrhea was the dose-limiting toxicity. Eleven of the 17 patients with primary rectal cancer underwent a sphincter-sparing procedure. One patient had a pathologic complete response. CONCLUSION: Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well tolerated. Additional investigation is warranted.

Cochrane Review: Screening programmes for developmental dysplasia of the hip in newborn infants.

BACKGROUND: Uncorrected developmental dysplasia of the hip (DDH) is associated with long-term morbidity such as gait abnormalities, chronic pain and degenerative arthritis. OBJECTIVES: To determine the effect of different screening programmes for DDH on the incidence of late presentation of congenital hip dislocation. SEARCH METHODS: Searches were performed in CENTRAL (The Cochrane Library), MEDLINE and EMBASE (January 2011) supplemented by searches of clinical trial registries, conference proceedings, cross references and contacting expert informants. SELECTION CRITERIA: Randomised, quasi-randomised or cluster trials comparing the effectiveness of screening programmes for DDH. DATA COLLECTION AND ANALYSIS: Three independent review authors assessed study eligibility and quality, and extracted data. MAIN RESULTS: No study examined the effect of screening (clinical and/or ultrasound) and early treatment versus not screening and later treatment. One study reported universal ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery but was associated with a significant increase in treatment. One study reported targeted ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery, with no significant difference in rate of treatment. Meta-analysis of two studies found universal ultrasound compared to targeted ultrasound did not result in a significant reduction in late diagnosed DDH or surgery. There was heterogeneity between studies reporting the effect on treatment rate. Meta-analysis of two studies found delayed ultrasound and targeted splinting compared to immediate splinting of infants with unstable (but not dislocated) hips resulted in no significant difference in the rate of late diagnosed DDH. Both studies reported a significant reduction in treatment with use of delayed ultrasound and targeted splinting. One study reported delayed ultrasound and targeted splinting compared to immediate splinting of infants with mild hip dysplasia on ultrasound resulted in no significant difference in late diagnosed DDH but a significant reduction in treatment. No infants in either group received surgery. AUTHORS' CONCLUSIONS: There is insufficient evidence to give clear recommendations for practice. There is inconsistent evidence that universal ultrasound results in a significant increase in treatment compared to the use of targeted ultrasound or clinical examination alone. Neither of the ultrasound strategies have been demonstrated to improve clinical outcomes including late diagnosed DDH and surgery. The studies are substantially underpowered to detect significant differences in the uncommon event of late detected DDH or surgery. For infants with unstable hips or mildly dysplastic hips, use of delayed ultrasound and targeted splinting reduces treatment without significantly increasing the rate of late diagnosed DDH or surgery. PLAIN LANGUAGE SUMMARY: Screening methods for dislocated or improperly formed hips in newborn infants The hip joint is a ball and socket joint. Newborns may have hips that are not in their socket (dislocated) or hips that are improperly formed (dysplasia). Risk factors for hip dysplasia include a family history of a similar problem and female infants delivered in the breech position. The hips of most newborns will be examined clinically after birth and during infancy to determine whether they are stable, unstable or dislocated. Screening for hip dysplasia may prevent the need for late treatment, which is associated with long term hip deformity, gait disturbance and arthritis. However, early screening leads to increased treatment. Treatment may be complicated by damage to the hip due to impairment of the blood supply (avascular necrosis). This review found no studies that compared the benefits and costs of early screening versus not screening for hip problems. Studies that compared the addition of ultrasound to clinical examination reported that when ultrasound was performed on all infants, the rate of treatment increased with no significant difference in rate of late detected dysplasia or surgery. Targeted ultrasound to infants at high risk of hip dysplasia did not significantly increase the rate of treatment but also did not significantly reduce the rate of late detected dysplasia or surgery. It is not possible to give clear recommendations for hip screening of newborn infants from the available evidence. Where infants are clinically detected as having unstable but not dislocated hips, or are detected on ultrasound to have mild hip dysplasia, there is evidence that delaying treatment by two to eight weeks reduces the need for treatment without a significant increase in late diagnosed dysplasia or surgery.

Screening programmes for developmental dysplasia of the hip in newborn infants

BACKGROUND Uncorrected developmental dysplasia of the hip (DDH) is associated with long term morbidity such as gait abnormalities, chronic pain and degenerative arthritis. OBJECTIVE To determine the effect of different screening programmes for DDH on the incidence of late presentation of congenital hip dislocation. METHODS Search methods: Searches were performed in CENTRAL (The Cochrane Library), MEDLINE and EMBASE (January 2011) supplemented by searches of clinical trial registries, conference proceedings, cross references and contacting expert informants. Selection criteria: Randomized, quasi-randomized or cluster trials comparing the effectiveness of screening programmes for DDH. Data collection and analysis: Three independent review authors assessed study eligibility and quality, and extracted data. MAIN RESULTS No study examined the effect of screening (clinical and/or ultrasound) and early treatment versus not screening and later treatment. AUTHORS' CONCLUSIONS There is insufficient evidence to give clear recommendations for practice. There is inconsistent evidence that universal ultrasound results in a significant increase in treatment compared to the use of targeted ultrasound or clinical examination alone. Neither of the ultrasound strategies have been demonstrated to improve clinical outcomes including late diagnosed DDH and surgery. The studies are substantially underpowered to detect significant differences in the uncommon event of late detected DDH or surgery. For infants with unstable hips or mildly dysplastic hips, use of delayed ultrasound and targeted splinting reduces treatment without significantly increasing the rate of late diagnosed DDH or surgery. .

The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients.

Impairment of dendritic cells (DC), the most effective activators of anticancer immune responses, is one mechanism for defective antitumor immunity, but the causes of DC impairment are incompletely understood. We evaluated the association of impaired DC differentiation with angiogenesis-associated molecules D-dimer, vascular endothelial growth factor (VEGF), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor (PAI-1) in peripheral blood from 41 patients with lung, breast, and colorectal carcinoma. Subsequently, we studied the effect of administration of the anti-VEGF antibody (bevacizumab) on DC maturation and function in vivo. Compared with healthy volunteers, cancer patients had a bias toward the immunoregulatory DC2, had deficits in DC maturation after overnight in vitro culture, and had a significant increase in immature myeloid cell progenitors of DC (0.50 +/- 0.31% vs. 0.32 +/- 0.16% of peripheral blood mononuclear cells, respectively, P = 0.011). A positive correlation was found between the percentage of DC2 and PAI-1 (R = 0.50) and between immature myeloid cells and VEGF (R = 0.52). Bevacizumab administration to cancer patients was associated with a decrease in the accumulation of immature progenitor cells (0.39 +/- 0.30% vs. 0.27 +/- 0.24%, P = 0.012) and induced a modest increase in the DC population in peripheral blood (0.47 +/- 0.23% vs. 0.53 +/- 0.30%). Moreover, anti-VEGF antibody treatment enhanced allo-stimulatory capacity of DC and T cell proliferation against recall antigens. These data suggest that DC differentiation is negatively associated with VEGF levels and may be one explanation for impaired anticancer immunity, especially in patients with advanced malignancies.

A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract.

PURPOSE: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. METHODS AND MATERIALS: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m(2) q12h)/5-FU (starting at 0.6 mg/m(2) q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. RESULTS: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m(2) q12h/1 mg/m(2) q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. CONCLUSION: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.