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Sequential oxidative cleavage and double-Mannich reactions enable the stereoselective conversion of simple norbornenes into complex alkaloid-like structures. The products undergo a wide range of derivatization reactions, including regioselective enol triflate formation/cross-coupling sequences and highly efficient conversion to an unusual tricyclic 8,5,5-fused lactam. Overall, the process represents a formal one-atom aza-ring expansion with concomitant bridging annulation, making it of interest for the broader derivatization of alkene feedstocks.
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BACKGROUND: Although multiple specialties perform neonatal circumcision (NC), overall NC proceduralist availability is limited. The approach to training new practitioners varies. This study aims to describe NC training experiences, current practices, and make suggestions for future improvements. METHODS: Perinatal physicians across 11 hospitals in a large Midwestern United States city who perform NC or who conduct newborn examinations and provide circumcision counseling were recruited for semistructured interviews about NC care. Interviews were transcribed; training-related comments underwent inductive and deductive qualitative coding. Themes related to circumcision training and recommendations for improving the experience of future circumcision learners were summarized. RESULTS: Twenty-three physicians (10 family medicine, 8 pediatrics, and 5 obstetrics; 78% currently perform circumcision) participated. All participants conducted newborn examinations and provided circumcision counseling, but only 21/23 were trained to perform circumcision. Several themes related to training emerged: (1) personal training experience, (2) training others to perform circumcision, and (3) current training needs and barriers. Most reported learning in residency by a "see one, do one, teach one" approach with minimal formal didactic or structured training. Compared with their personal experience, participants noted a shift toward more direct supervision and preprocedure preparation for current trainees. However, most reported that circumcision learning continues to be "hands-on." Participants desired a more structured approach for future trainees. CONCLUSIONS: Perinatal physicians noted a shift in the current NC training to a more hands-on approach than they experienced personally. Development of a structured NC curriculum was recommended to improve training.
Subject(s)
Circumcision, Male , Humans , Circumcision, Male/education , Male , Infant, Newborn , Female , Clinical Competence/standards , Pediatrics/education , Midwestern United States , Interviews as TopicABSTRACT
OBJECTIVE: Over half of infant boys born in the United States undergo newborn circumcision. However, available data indicate that boys who are publicly insured, or Black/African American, have less access to desired newborn circumcision, thus concentrating riskier, more costly operative circumcision among these populations. This study ascertains perinatal physician perspectives about barriers and facilitators to providing newborn circumcisions, with a goal of informing future strategies to ensure more equitable access. METHODS: Qualitative interviews about newborn circumcision care were conducted from April-June 2020 at eleven Chicago-Area hospitals. Physicians that provide perinatal care (pediatricians, family medicine physicians, and obstetricians) participated in qualitative interviews about newborn circumcision. Inductive and deductive qualitative coding was performed to identify themes related to barriers and facilitators of newborn circumcision care. RESULTS: The 23 participating physicians (78% female, 74% white, median 16 years since medical school graduation [range 5-38 years], 52% hospital leadership role, 78% currently perform circumcisions) reported multiple barriers including difficulty with procedural logistics and inconsistent clinician availability and training; corresponding suggestions for operational improvements were also provided. Regarding newborn circumcision insurance coverage and reimbursement, physicians reported limited knowledge, but noted that some insurance reimbursement policies financially disincentivize clinicians and hospitals from offering inpatient newborn circumcision. CONCLUSIONS: Physicians identified logistical/operational, and reimbursement-related barriers to providing newborn circumcision for desirous families. Future studies and advocacy work should focus on developing clinical strategies and healthcare policies to ensure equitable access, and incentivize clinicians/hospitals to perform newborn circumcisions.
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Circumcision, Male , General Practitioners , Male , Infant , Infant, Newborn , Humans , United States , Female , Insurance Coverage , Pediatricians , ChicagoABSTRACT
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria. OBJECTIVE: The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease. STUDY DESIGN: We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression. RESULTS: The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75 % of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43 % vs 3 %), lower eGFR at diagnosis (median = 52 mL/min/1.73 m2 vs 114 mL/min/1.73 m2), and have normal mobility. Patients with PH1 had higher proportion of calcium oxalate monohydrate kidney stones than controls (median = 100 % vs 10 %). There were no differences in diagnosis of failure to thrive, stone size, or echocardiography results. CONCLUSIONS: Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.
Subject(s)
Hyperoxaluria, Primary , Kidney Calculi , Kidney Failure, Chronic , Nephrocalcinosis , Nephrolithiasis , Adolescent , Humans , Child , Nephrocalcinosis/diagnosis , Calcium Oxalate/metabolism , Case-Control Studies , Kidney Failure, Chronic/etiology , Kidney Calculi/etiology , Kidney Calculi/complicationsABSTRACT
The past decade has seen the increasing influence and relevance of real-world data (RWD) and real-world evidence (RWE) in healthcare decision making. The value added by RWD/RWE has prompted the pharmaceutical industry to develop high performing systems and practices to harness the power of evidence generated at the global level. However, this worldwide transformation provides outstanding opportunities to support capability building within local affiliates and to impact key country-level stakeholders through resulting evidence. Therefore, we present an Evidence Blueprint Initiative, which links the global and local ("glocal") skills, and furthermore addresses the opportunities and gaps in evidence generation capabilities at the local level. Cross-functional experts were recruited at the local, regional, and global level to define best practices. A framework was developed to characterize the foundational expertise needed and to assess markets' existing capabilities. Subsequently, targeted roadmaps were developed and implemented to build capabilities in specific areas within each affiliate. The impact from the Blueprint is encouraging, resulting in improved local evidence plans, established evidence teams, enhanced RWD use and strategic implementation of patient centric science in local affiliates. The success of the Blueprint resides in empowering affiliates to realise their local evidence generation ambitions and to match them to their local context. It strengthens and expands the ties between various parts of the organisation and the external environment while building fit-for-future evidence capabilities from local affiliates.
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Significance: High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in ex vivo FT and ovaries with good sensitivity and specificity. Multispectral fluorescence imaging (MFI) can differentiate healthy, benign, and malignant ovarian and FT tissues. Optical coherence tomography (OCT) reveals subsurface microstructural information and can distinguish normal and cancerous structure in ovaries and FTs. Aim: We developed an FT endoscope, the falloposcope, as a method for detecting ovarian cancer with MFI and OCT. The falloposcope clinical prototype was tested in a pilot study with 12 volunteers to date to evaluate the safety and feasibility of FT imaging prior to standard of care salpingectomy in normal-risk volunteers. In this manuscript, we describe the multiple modifications made to the falloposcope to enhance robustness, usability, and image quality based on lessons learned in the clinical setting. Approach: The â¼0.8 mm diameter falloposcope was introduced via a minimally invasive approach through a commercially available hysteroscope and introducing a catheter. A navigation video, MFI, and OCT of human FTs were obtained. Feedback from stakeholders on image quality and procedural difficulty was obtained. Results: The falloposcope successfully obtained images in vivo. Considerable feedback was obtained, motivating iterative improvements, including accommodating the operating room environment, modifying the hysteroscope accessories, decreasing endoscope fragility and fiber breaks, optimizing software, improving fiber bundle images, decreasing gradient-index lens stray light, optimizing the proximal imaging system, and improving the illumination. Conclusions: The initial clinical prototype falloposcope was able to image the FTs, and iterative prototyping has increased its robustness, functionality, and ease of use for future trials.
Subject(s)
Fallopian Tubes , Ovarian Neoplasms , Female , Humans , Pilot Projects , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , EndoscopesABSTRACT
OBJECTIVE: To explore private vs public pediatric circumcision insurance coverage and surgeon reimbursement. METHODS: A telephone survey about circumcision coverage (Current Procedural Terminology codes: 54150, 54161) was conducted in October 2021 with insurance plan representatives from the 12 plans that comprised ≥1% of institutional pediatric urology visits to compare plan characteristics and coverage details. Circumcision billing data were collected at one pediatric hospital to assess surgeon reimbursement (insurance+patient payment) by plan type using bivariate statistics. RESULTS: Ten plans (5 private and 5 public) responded (83.3% response rate). All except one public plan covered newborn circumcision. For non-newborn circumcisions, most public plans (80%) had unrestricted coverage, whereas all private plans required medical necessity. Median reimbursement for newborn circumcision (CPT: 54150) was $484 for private and $78 for public plans, Pâ¯<â¯.001 while median reimbursement for non-newborn circumcision (CPT: 54161) was $314 for private and $147 for public plans, Pâ¯<â¯.001. CONCLUSION: Private insurance plans reimburse significantly more than public plans for newborn circumcision. For non-newborn circumcision, private plans reimburse more than public but the coverage is more restricted, with a smaller differential between newborn and non-newborn circumcision. This coverage and reimbursement structure may indirectly encourage newborn circumcision for privately insured boys and non-newborn circumcision for publicly insured boys.
Subject(s)
Circumcision, Male , Surgeons , Male , Infant, Newborn , Humans , Child , United States , Insurance Coverage , Hospitals, Urban , Health FacilitiesABSTRACT
BACKGROUND: Individuals with nephrolithiasis frequently present to the Emergency Department (ED). Safety and quality principles are often applied in pediatric EDs to children presenting with nephrolithiasis, such as limiting ionizing radiation exposure and opioid analgesics. However, it is unknown whether pediatric EDs apply these same principles to adult patients who present with nephrolithiasis. We hypothesized that adult patients would be associated with higher use of radiation-based imaging and opioid analgesics. OBJECTIVE: To assess variations in diagnostic and treatment interventions and hospital utilization between pediatric and adult patients presenting to the pediatric ED with nephrolithiasis. STUDY DESIGN: A retrospective cohort study was conducted, examining outcomes for pediatric (<18-years-old) versus adult (≥18-years-old) patients in 42 pediatric EDs from 2009 to 2020 using the Pediatric Health Information System (PHIS) database. Patients with an ICD-9/10 principal diagnosis code of nephrolithiasis with no nephrolithiasis-related visits within the prior 6 months were included. Primary outcomes were imaging, medications, and surgical interventions. Secondary outcomes were hospital admissions, 90-day ED revisits, and 90-day readmissions. Generalized linear mixed models with random effects were used to adjust for confounding and clustering. RESULTS: In total, 16,117 patients with 17,837 encounters were included. Most hospitals were academic (95.2%), and a plurality were located in the South (38.1%). Most patients were <18-years-old (84.4%, median (interquartile range): 15 (12-17)-years-old), female (57.9%), and White (76.3%), and 17.1% were Hispanic/Latino. Most had no complex chronic conditions (89.2%) and no chronic disease per pediatric medical complexity algorithm (51.5%). For the primary outcome, adults, relative to pediatric patients, who presented to the pediatric ED with nephrolithiasis had higher adjusted odds of receiving computerized tomography (CT) scans (Odds Ratio [OR] 1.43 [95% Confidence Interval [CI] 1.29-1.59]) and opioid analgesics (OR 1.45 [95%CI 1.33-1.58]) (Summary Figure). Secondary outcomes showed that adults, relative to pediatric patients, had lower adjusted odds of hospital admissions, 90-day ED revisits, and 90-day readmissions. DISCUSSION: Our results suggest that certain pediatric safety and quality principles, such as limiting ionizing radiation exposure and opioid analgesic prescriptions, are not being equally applied to pediatric and adult patients who present to pediatric EDs with nephrolithiasis. The mechanism of these findings remains to be elucidated. CONCLUSIONS: Variations in care for individuals with nephrolithiasis reflect an opportunity for quality improvement in pediatric EDs and inform work exploring optimal care pathways for all patients presenting to the pediatric ED with nephrolithiasis.
Subject(s)
Analgesics, Opioid , Kidney Calculi , Child , United States/epidemiology , Humans , Adult , Female , Adolescent , Analgesics, Opioid/therapeutic use , Retrospective Studies , Tertiary Healthcare , Emergency Service, Hospital , Kidney Calculi/drug therapy , Chronic DiseaseABSTRACT
INTRODUCTION: In 2011, the American Academy of Pediatrics (AAP) published guidelines regarding diagnosis and management of children 2-to-24-months-old with initial febrile urinary tract infection (fUTI). Available data were insufficient to determine whether evidence from studies of 2-to-24-month-olds applies to those <2-months-old, so they were excluded. OBJECTIVE: This study aimed to 1) compare demographic, clinical, imaging and outcomes between patients <2-months-old and those 2-to-24-months-old hospitalized with fUTI, and 2) assess whether diagnostic and imaging recommendations of the AAP 2011 guidelines apply to those <2-months-old. STUDY DESIGN: A cohort study of patients ≤24-months-old hospitalized at a children's hospital with fUTI from 2016 to 2018 was conducted. Data were collected via a prospectively generated electronic medical record note template, supplemented with retrospective chart review. Primary outcomes included differences in demographics, clinical presentation, urine culture results, and imaging utilization/results by age group. Secondary outcomes included surgical procedures, UTI recurrence, and 90-day all-cause readmissions and emergency department (ED) revisits. Univariate and bivariate statistics were utilized to compare age groups. RESULTS: Overall, 137 patients were included (median age 70 days, 55.5% male [92.1% uncircumcised], 53.3% Hispanic/Latino, 89.8% 1st fUTI). There were no demographic differences between groups, except children <2-months-old were more frequently male (71.2 vs 43.6%, p = 0.002). The Summary Table compares clinical factors and imaging utilization by age. There were no differences in urinalysis or urine culture results between groups. Patients <2-months-old had shorter fever duration, lower maximum temperature, and lower white blood cell counts. Voiding cystourethrograms (VCUGs) were recommended and obtained more frequently in patients <2-months-old, but there were no differences in renal and bladder ultrasound (RBUS) or VCUG results between age groups. There were no differences in UTI recurrence (13.6% of <2-months-old vs 14.1% of 2-to-24-months-old, p = 1.00) or fUTI recurrence (13.6 vs 7.7%, p = 0.40) within 1 year, 90-day readmission (6.8 vs 6.4%, p = 1.00), or 90-day ED revisit (22.0 vs 20.5%, p = 1.00). DISCUSSION: There were minimal differences between the <2-months-old and 2-to-24-months-old age groups in demographics, laboratory (including microbial) or imaging results, or clinical outcomes. Patients <2-months-old were more frequently male and less ill. These data support applying urinalysis and urine culture diagnostic criteria, and universal RBUS, from the AAP guidelines to patients <2-months-old. Given utilization differences, applicability of VCUG guideline recommendations requires further clarification for patients <2-months-old. CONCLUSION: Laboratory testing and RBUS recommendations from the AAP guidelines may be safely applied to infants <2-months-old. Further studies are needed to clarify optimal VCUG recommendations.
Subject(s)
Urinary Tract Infections , Vesico-Ureteral Reflux , Humans , Child , United States , Infant , Male , Child, Preschool , Female , Vesico-Ureteral Reflux/diagnosis , Retrospective Studies , Cohort Studies , Urinary Tract Infections/diagnostic imaging , Urinary Tract Infections/complications , Urinary BladderABSTRACT
PURPOSE: We systematically reviewed the variability in definitions of kidney abnormality (KA) outcomes in individuals with spina bifida (SB). MATERIALS AND METHODS: A systematic scoping review was conducted using MEDLINE, Embase™, Cochrane Library, CINAHL, PsycInfo®, Web of Science™ and ClinicalTrials.gov for articles from time of database inception to September 2020. No language or patient age restrictions were applied. Primary research articles involving individuals with SB where KA was assessed as an outcome were included. Means of assessing KA and defining KA severity were abstracted. RESULTS: Of 2,034 articles found, 274 were included in the review. Most articles were published after 1990 (63.5%) and included pediatric-only populations (0-18 years; 60.5%). KA outcomes were identified by imaging-based anatomical outcomes (84.7%), serum-based outcomes (44.9%), imaging-based functional outcomes (5.5%), urine-based outcomes (3.3%) and diagnoses of end-stage kidney disease (2.6%) or chronic kidney disease otherwise unspecified (1.8%). Hydronephrosis was the most commonly used specific outcome (64.6%, 177/274) with 19.8% (35/177) of articles defining hydronephrosis severity. Hydronephrosis was used more frequently in articles with pediatric-only populations. Creatinine and cystatin-C were used in 82.1% (101/123) and 17.9% (22/123) of articles reporting serum-based outcomes, respectively, with 32.7% and 50.0% of articles defining estimated glomerular filtration rate (GFR) severity. Serum-based outcomes were more common in articles including adults >18 years. Measured GFR was assessed in 9.9% (27/274) of articles, with 44.4% (12/27) of articles defining GFR severity. CONCLUSIONS: Significant variability exists in how authors define KA with few specifically defining KA severity. Consensus and consistency in defining KA outcomes are needed.
Subject(s)
Hydronephrosis , Renal Insufficiency, Chronic , Spinal Dysraphism , Adult , Child , Female , Glomerular Filtration Rate , Humans , Kidney/diagnostic imaging , Male , Spinal Dysraphism/diagnosisABSTRACT
The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62-13.44) months for first-line treatment, and 4.4 (95% CI: 1.47-7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9-30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5-27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Quebec , Retrospective StudiesABSTRACT
BACKGROUND: A significant proportion of boys present to surgical specialists later in infancy/early childhood for elective operative circumcision despite the higher procedural risks. This study aims to assess physician perspectives on access to neonatal circumcision across the United States and identify potential reasons contributing to disparities in access. METHODS: A cross-sectional survey was electronically distributed to physician members of the Societies for Pediatric Urology and the American Academy of Pediatrics Section on Hospital Medicine. Hospital characteristics and circumcision practices were assessed. Associations between NC availability and institutional characteristics were evaluated using chi-squared testing and multivariable logistic regression. Qualitative analyses of free-text comments were performed. RESULTS: A total of 367 physicians responded (129 urologists [41%], 188 pediatric hospitalists [59%]). Neonatal circumcision was available at 86% of hospitals represented. On univariate and multivariate analysis, the 50 hospitals that did not offer neonatal circumcision were more likely to be located in the Western region (odds ratio [OR] = 8.33; 95% confidence interval [CI] 3.1-25 vs. Midwest) and in an urban area (OR = 4.2; 95% CI 1.6-10 vs. suburban/rural) compared with hospitals that offered neonatal circumcision. Most common reasons for lack of availability included not a birth hospital (N = 22, 47%), lack of insurance coverage (N = 8, 17%), and low insurance reimbursement (N = 7, 15%). Institutional, regional, or provider availability (68%), insurance/payment (12.4%), and ethics (12.4%) were common themes in the qualitative comments. CONCLUSIONS: Overall availability of neonatal circumcision varied based on hospital characteristics, including geography. Information from this survey will inform development of interventions designed to offer neonatal circumcision equitably and comprehensively.
Subject(s)
Circumcision, Male/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Health Surveys , Healthcare Disparities/statistics & numerical data , Cross-Sectional Studies , Hospitalists , Hospitals , Humans , Infant, Newborn , Insurance Coverage , Insurance, Health, Reimbursement , Male , Practice Patterns, Physicians' , United States , UrologistsABSTRACT
INTRODUCTION: Genotyping circulating tumor DNA (ctDNA) is a promising noninvasive clinical tool to identify the EGFR T790M resistance mutation in patients with advanced NSCLC with resistance to EGFR inhibitors. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicenter study to standardize T790M mutation detection using plasma ctDNA testing. METHODS: In phase 1, commercial reference standards were distributed to participating clinical laboratories, to use their existing platforms for mutation detection. Baseline performance characteristics were established using known and blinded engineered plasma samples spiked with predetermined concentrations of T790M, L858R, and exon 19 deletion variants. In phase II, peripheral blood collected from local patients with known EGFR activating mutations and progressing on treatment were assayed for the presence of EGFR variants and concordance with a clinically validated test at the reference laboratory. RESULTS: All laboratories in phase 1 detected the variants at 0.5 % and 5.0 % allele frequencies, with no false positives. In phase 2, the concordance with the reference laboratory for detection of both the primary and resistance mutation was high, with next-generation sequencing and droplet digital polymerase chain reaction exhibiting the best overall concordance. Data also suggested that the ability to detect mutations at clinically relevant limits of detection is generally not platform-specific, but rather impacted by laboratory-specific practices. CONCLUSIONS: Discrepancies among sending laboratories using the same assay suggest that laboratory-specific practices may impact performance. In addition, a negative or inconclusive ctDNA test should be followed by tumor testing when possible.
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BACKGROUND: Treatment strategies for metastatic non-small cell lung cancer (NSCLC) are evolving rapidly and can be highly variable. Real-world evidence of treatment patterns and outcomes can provide an understanding of our current practice and offer insights on ways to incorporate emerging therapies into our treatment paradigm. In this population-based study, we investigated treatments and outcomes of stage IV NSCLC patients from a large Canadian province. METHODS: Patients diagnosed with de novo stage IV NSCLC from April 1, 2010 to March 31, 2015 were identified. Data for baseline characteristics, treatments, and outcomes were obtained from provincial data sources, including the cancer registry and electronic medical records. We classified systemic treatments as chemotherapy, targeted therapy (anti-epidermal growth factor receptor, and anti-anaplastic lymphoma kinase) and immunotherapy (checkpoint inhibitors) and characterized clinical outcomes by treatment type. RESULTS: A total of 6438 patients were identified with NSCLC, of whom 3606 (56%) had de novo stage IV disease. The median age of diagnosis was 69 (range: 20 to 100) years and 52.4% were men. First-line palliative treatments included: chemotherapy in 19.5% (n=703), targeted agents in 5.7% (n=204), immunotherapy in 1% (n=1), radiotherapy in 6.8% (n=246), and best supportive care in 74.8% (n=2,698). Median overall survival (mOS) from diagnosis for the whole cohort was 3.8 months. Within subgroups, mOS was 18.0 months for targeted therapies, 9.4 months for chemotherapy, and 2.5 months for best supportive care. Only 1.0% of patients (n=34) received immunotherapy at any line. CONCLUSIONS: Survival benefit was dependent on type of treatment received, with significantly better mOS observed with the use of small-molecule targeted therapy against epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements, as compared with best supportive care.
Subject(s)
Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Canada , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Survival Rate , Treatment Outcome , Young AdultABSTRACT
Background: In 2020, approximately 3100 Canadian women were diagnosed with ovarian cancer (OC), with 1950 women dying of this disease. Prognosis for OC remains poor, with 70% to 75% of cases diagnosed at an advanced stage and an overall 5-year survival of 46%. Current standard of care in Canada involves a combination of cytoreductive surgery and platinum-based chemotherapy. Objective: There are few studies reporting current OC costs. This study sought to determine patient characteristics and costs to the health system for OC in Ontario, Canada. Methods: Women diagnosed with OC in Ontario between 2010 and 2017 were identified. The cohort was linked to provincial administrative databases to capture treatment patterns, survival, and costs. Overall total and mean cost per patient (unadjusted) were reported in 2017 Canadian dollars, using a macro-based costing methodology called GETCOST. It is programmed to determine the costs of short-term and long-term episodes of health-care resources utilized. Results: Of the 2539 OC patients included in the study, the mean age at diagnosis was 60.4±11.35 years. The majority were diagnosed with stage III disease (n=1247). The only treatment required for 74% of stage I patients and 54% of stage II patients was first-line (1L) platinum chemotherapy; in advanced stages (III/IV) 24% and 20%, respectively, did not receive further treatment after 1L therapy. The median overall survival (mOS) for the whole cohort was 5.13 years. Survival was highest in earlier stage disease (mOS not reached in stage I/II), and dropped significantly in advanced stage patients (stage III: mOS=4.09 years; stage IV: mOS=3.47 years). Overall mean costs in patients stage I were CAD $58 099 compared to CAD $124 202 in stage IV. Discussion: The majority of OC patients continue to be diagnosed with advanced disease, which is associated with poor survival and increased treatment costs. Increased awareness and screening could facilitate diagnosis of earlier stage disease and reduce high downstream costs for advanced disease. Conclusion: Advanced OC is associated with poor survival and increased costs, mainly driven by hospitalizations or cancer clinic visits. The introduction of new targeted therapies such as olaparib could impact health system costs, by offsetting higher downstream costs while also improving survival.
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Over half of boys in the United States undergo circumcision, which has its greatest health benefits and lowest risks when performed during the newborn period under local anesthesia. The COVID-19 pandemic has affected delivery of patient care in many ways and likely also influenced the provision of newborn circumcisions. Prior to the pandemic, we planned to conduct a qualitative study to ascertain physician perspectives on providing newborn circumcision care. The interviews incidentally coincided with the onset of the pandemic and thus, pandemic-related changes emerged as a theme. We elected to analyze this theme in greater detail. Semi-structured interviews were conducted with perinatal physicians in a large urban city from 4/2020 to 7/2020. Physicians that perform or counsel regarding newborn circumcision and physicians with knowledge of or responsibility for hospital policies were eligible. Interviews were transcribed verbatim and qualitative coding was performed. Twenty-three physicians from 11 local hospitals participated. Despite no specific COVID-19 related questions in the interview guide, nearly half of physicians identified that the pandemic affected delivery of newborn circumcision care with 8 pandemic-related sub-themes. The commonest sub-themes included COVID-19 related changes in: (1) workflow processes, (2) staffing and availability of circumcision proceduralists, and (3) procedural settings. In summary, this qualitative study revealed unanticipated COVID-19 pandemic-related changes with primarily adverse effects on the provision of desired newborn circumcisions. Some of these changes may become permanent resulting in broad implications for policy makers that will likely need to adapt and redesign the processes and systems for the delivery of newborn circumcision care.
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BACKGROUND: Most patients with stage III non-small cell lung cancer (NSCLC) develop metastases and succumb to their cancer. Approaches to the treatment of stage III disease can be highly variable. Understanding current treatment patterns can inform the optimal integration of emerging therapies. In this study, we describe contemporary treatment patterns and outcomes for a population-based cohort of stage III NSCLC patients from a large Canadian province. METHODS: On the basis of the provincial cancer registry, all adult patients diagnosed with stage III NSCLC from April 1, 2010 to March 31, 2015 were identified. Analyses of these patients' existing electronic medical records and administrative claims data were conducted to describe patient characteristics, treatment patterns, and survival outcomes. RESULTS: In total, we screened 6438 patients diagnosed with NSCLC, of whom 1151 (17.9%) had stage III disease. Among them, 61.2% were stage IIIA, 36.4% were stage IIIB, and 2.4% were unspecified. Median age at diagnosis was 70 (22 to 94) years and 50.2% were men. In this cohort, a significant proportion of patients received only palliative radiotherapy (35.6%), palliative chemotherapy (8.8%), or best supportive care (24.8%) as initial treatment. Conversely, relatively few underwent concurrent chemoradiotherapy (11.7%) or trimodality therapy (1.7%). Surgery±adjuvant treatments were performed in 14.8% of stage III patients. Median overall survival was 13.2 months (95% confidence interval [CI], 12.2-14.0) among stage III patients. Patients who received initial curative treatment had statistically significant better survival compared with those who received noncurative treatment (P<0.001); median overall survival 29.8 months (95% CI, 22.3-34.6) and 8.9 months (95% CI, 7.6-11.6), respectively. CONCLUSIONS: In a population-based setting that includes community, regional, and tertiary cancer centers, use of concurrent chemoradiotherapy and trimodality therapy in stage III NSCLC was low despite evidence supporting the potential benefits of these strategies.
Subject(s)
Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Non-Small-Cell Lung/therapy , Combined Modality Therapy/statistics & numerical data , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Alberta , Carcinoma, Non-Small-Cell Lung/surgery , Chemoradiotherapy/statistics & numerical data , Female , Humans , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Palliative Care/statistics & numerical data , Registries , Rural Population/statistics & numerical data , Survival Rate , Urban Population/statistics & numerical data , Young AdultABSTRACT
BACKGROUND: As the treatment landscape in patients with non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFRm) continues to evolve, real-world health utility scores (HUS) become increasingly important for economic analyses. METHODS: In an observational cohort study, questionnaires were completed in EGFRm NSCLC outpatients, to include demographics, EQ-5D-based HUS and patient-reported toxicity and symptoms. Clinical and radiologic characteristics together with outcomes were extracted from chart review. The impact of health states, treatment type, toxicities, and clinical variables on HUS were evaluated. RESULTS: Between 2014 and 2018, a total of 260 patients completed 994 encounters. Across treatment groups, patients with disease progression had lower HUS compared to controlled disease (0.771 vs 0.803; P = .01). Patients predominantly received gefitinib as the first-line EGFR tyrosine kinase inhibitor (TKI) (n = 157, mean-HUS = 0.798), whereas osimertinib (n = 62, mean-HUS = 0.806) and chemotherapy (n = 38, mean-HUS = 0.721) were more likely used in subsequent treatment lines. In longitudinal analysis, TKIs retained high HUS (>0.78) compared to chemotherapy (HUS < 0.74). There were no differences between the frequency or severity of toxicity scores in patients receiving gefitinib compared to osimertinib; however, TKI therapy resulted in fewer toxicities than chemotherapy (P < .05), with the exception of worse diarrhea and skin rash (P < .001). Severity in toxicities inversely correlated with HUS (P < .001). Clinico-demographic factors significantly affecting HUS included age, Eastern Cooperative Oncology Group Performance Score (ECOG PS), disease state, treatment group, and metastatic burden. CONCLUSIONS: In a real-world EGFRm population, patients treated with gefitinib or osimertinib had similar HUS and toxicities, scores which were superior to chemotherapy. Health utility scores inversely correlated with patient-reported toxicity scores. In the era of targeted therapies, future economic analyses should incorporate real-world HUS.
Subject(s)
Carcinoma, Non-Small-Cell Lung/epidemiology , ErbB Receptors , Lung Neoplasms/epidemiology , Patient Acceptance of Health Care , Protein Kinase Inhibitors , Aged , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Disease Management , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Middle Aged , Mutation , Neoplasm Staging , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Treatment OutcomeABSTRACT
Bordetella pertussis testing performed using real-time polymerase chain reaction (RT-PCR) is interpreted based on a cycle threshold (Ct) value. At Public Health Ontario Laboratories (PHOL), a Ct value <36 is reported as positive, and Ct values ≥36 and <40 are reported as indeterminate. PHOL reported indeterminate results to physicians and public health units until May 2012, after which these results were only reported to physicians. We investigated the association between Ct value and disease symptom and severity to examine the significance of indeterminate results clinically, epidemiologically and for public health reporting. B. pertussis positive and indeterminate RT-PCR results were linked to pertussis cases reported in the provincial Integrated Public Health Information System (iPHIS), using deterministic linkage. Patients with positive RT-PCR results had a lower median age of 10.8 years compared to 12.0 years for patients with indeterminate results (p = 0.24). Hospitalized patients had significantly lower Ct values than non-hospitalized patients (median Ct values of 20.7 vs. 31.6, p<0.001). The proportion of patients reporting the most indicative symptoms of pertussis did not differ between patients with positive vs. indeterminate RT-PCR results. Taking the most indicative symptoms of pertussis as the gold-standard, the positive predictive value of the RT-PCR test was 68.1%. RT-PCR test results should be interpreted in the context of the clinical symptoms, age, vaccination status, prevalence, and other factors. Further information on interpretation of indeterminate RT-PCR results may be needed, and the utility of reporting to public health practitioners should be re-evaluated.