Factors Influencing Time-to-diagnosis of Biliary Atresia.
ABSTRACT: OBJECTIVES:Diagnosing biliary atresia (BA) quickly is critical, because earlier treatment correlates with delayed or reduced need for liver transplantation. However, diagnosing BA quickly is also difficult, with infants usually treated after 60 days of life. In this study, we aim to accelerate BA diagnosis and treatment, by better understanding factors influencing the diagnostic timeline. METHODS:Infants born between 2007 and 2014 and diagnosed with BA at our institution were included (n?=?65). Two periods were examined retrospectively: P1, the time from birth to specialist referral, and P2, the time from specialist referral to treatment. How sociodemographic factors associate with P1 and P2 were analyzed with Kaplan-Meier curves and Cox proportional hazard models. In addition, to better characterize P2, laboratory results and early tissue histology were studied. RESULTS:P1 associated with race/ethnicity, with shorter times in non-Hispanic white infants compared to non-Hispanic black and Hispanic infants (P?=?0.007 and P?=?0.004, respectively). P2 associated with referral age, with shorter times in infants referred after 30, 45, or 60 days of life (P?
Project description:To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota (GM), and how ketogenic diet (KD) alters GM.A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR, and inter-group comparison was conducted by R software.After being on KD treatment for a week, 64% of epileptic infants showed an obvious improvement, with a 50% decrease in seizure frequency. GM structure in epileptic infants (P1 group) differed dramatically from that in healthy infants (Health group). Proteobacteria, which had accumulated significantly in the P1 group, decreased dramatically after KD treatment (P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group, in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.
Project description:<h4>Background</h4>Prolonged wait times are known barriers to accessing nephrology care for patients needing more urgent specialist services. Improved process and standardized triage systems are known to minimize wait times of urgent or semi-urgent care in health care disciplines. In Central Zone (CZ) renal clinic, mean wait times for urgent (P1) and semi-urgent (P2) referrals were prolonged before 2014. We also observed prolonged wait times for elective (P3-P5) categories. Improving wait times was identified as an access to care quality improvement focus in CZ renal clinic of the Nova Scotia Health Authority (NSHA).<h4>Objectives</h4>To describe our new referral process and new triage system, and to examine their effect on number of referrals wait-listed and mean wait times.<h4>Design</h4>A quasi-experimental design was used.<h4>Setting</h4>Halifax, Nova Scotia, Canada.<h4>Participants</h4>Patients referred to Central Zone Renal Clinic between 2012 and 2018.<h4>Measurements</h4>A time series of referral counts and wait times for each triage category were measured before our interventions and after implementing our interventions.<h4>Methods</h4>We reviewed our referral processes to identify gaps leading to prolonged wait times. On January 1, 2014, we implemented new administrative procedures: pretriage (standardized referral information form and staff training), triage (standardized clinic intake criteria and new triage guidelines), posttriage (protecting clinic spots for urgent and semi-urgent referrals, wait-list maintenance, and increasing new referral clinic capacity). Data were collected prospectively. Descriptive analysis on mean wait times was done using run charts.<h4>Results</h4>A 33% reduction in total number of referrals wait-listed was observed over 4.5 years after intervention. Descriptive analysis of the urgent and semi-urgent categories (P1 and P2) revealed a significant shift of mean wait times on run charts after the interventions. Target wait time was achieved in 94% of P1 category and 78% of P2 category.<h4>Limitations</h4>This type of study design does not exclude confounding variables influencing results. We did not explore stakeholder satisfaction or whether the new referral process presented barriers to resending referrals that had insufficient triage data. The long-term sustainability of adding demand-responsive surge clinics and opportunity cost were not assessed. Our referral process and triage system have not been externally validated and may not be applicable in settings without wait-lists or settings that use electronic, telephone or telemedicine consults.<h4>Conclusion</h4>Our selective intake of referrals with adequate triage information and referrals needing nephrology consult as defined by our clinic intake criteria reduced number of referrals wait-listed. We saw improved wait times for urgent and semi-urgent referrals with these categories now falling within target wait times for the vast majority of patients. The work of this improvement initiative continues especially for the lower-risk triage categories.<h4>Trial registration</h4>Not applicable as this was a Quality improvement initiative.
Project description:The specific specialist that a patient sees can have a large influence on the type of care they receive.We administered semistructured interviews with 47 men diagnosed with prostate adenocarcinoma between 2012 and 2014. Telephone interviews were recorded, transcribed, and analyzed using a systematic thematic approach.Three profiles of patients emerged for choosing specialists: active (21.3%), partially active (53.2%), and passive (25.5%). Active patients conducted substantial research when choosing a diagnosing urologist and a treating specialist: they searched online, consulted other men with prostate cancer, and/or visited multiple specialists for opinions. Partially active patients took only 1 additional step to find a treating specialist on their own after receiving a referral from their diagnosing urologist. Passive patients relied exclusively on referrals from their primary care physicians (PCPs) and diagnosing urologists.The majority of patients relied on their PCPs for referrals to diagnosing urologists and on their diagnosing urologists to choose the treating specialist. Given these findings and the significance of specialist choice in determining treatment, it is important that PCPs recognize their indirect but potentially important effect on treatment choice when making referrals for prostate cancer. PCPs should consider counseling patients about seeking second opinions from providers with different treatment perspectives and participating in treatment decisions.
Project description:In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommended a new strategy for the screening and diagnosis of gestational diabetes mellitus (GDM). However, no study has indicated that adopting the IADPSG recommendations improves perinatal outcomes. The objective of this study was to evaluate the effects of implementing the IADPSG criteria for diagnosing GDM on maternal and neonatal outcomes.Previously, we used a two-step approach (a 1-h, 50-g glucose challenge test followed by a 3-h, 100-g glucose tolerance test when indicated) to screen for and diagnose GDM. In July 2011, we adopted the IADPSG recommendations in our routine obstetric care. In this study, we retrospectively compared the rates of various maternal and neonatal outcomes in all women who delivered after 24 weeks of gestation during the periods before (P1, between January 1, 2009 and December 31, 2010) and after (P2, between January 1, 2012 and December 31, 2013) the IADPSG criteria were implemented. Pregnancies complicated by multiple gestations, fetal chromosomal or structural anomalies, and pre-pregnancy diabetes mellitus were excluded. Our results showed that the incidence of GDM increased from 4.6% using the two-step method to 12.4% using the IADPSG criteria. Compared to the women in P1, the women in P2 experienced less weight gain during pregnancy, lower birth weights, shorter labor courses, and lower rates of macrosomia (<4000 g) and large-for-gestational age (LGA) infants. P2 was a significant independent factor against macrosomia (adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.43-0.90) and LGA (adjusted OR 0.74, 95% CI 0.61-0.89) after multivariable logistic regression analysis.The adoption of the IADPSG criteria for diagnosis of GDM was associated with significant reductions in maternal weight gain during pregnancy, birth weights, and the rates of macrosomia and LGA.
Project description:HLA-DR molecules bind microbial peptides in an endosomal compartment and present them on the cell surface for CD4 T cell surveillance. HLA-DM plays a critical role in the endosomal peptide selection process. The structure of the HLA-DM-HLA-DR complex shows major rearrangements of the HLA-DR peptide-binding groove. Flipping of a tryptophan away from the HLA-DR1 P1 pocket enables major conformational changes that position hydrophobic HLA-DR residues into the P1 pocket. These conformational changes accelerate peptide dissociation and stabilize the empty HLA-DR peptide-binding groove. Initially, incoming peptides have access to only part of the HLA-DR groove and need to compete with HLA-DR residues for access to the P2 site and the hydrophobic P1 pocket. This energetic barrier creates a rapid and stringent selection process for the highest-affinity binders. Insertion of peptide residues into the P2 and P1 sites reverses the conformational changes, terminating selection through DM dissociation.
Project description:<h4>Background</h4>Immune checkpoint and BRAF-targeted inhibitors have demonstrated significant survival benefits for advanced melanoma patients within the context of clinical trials. We sought to determine their impact on overall survival (OS) at a population level in order to better understand the current landscape for patients diagnosed with clinical stage III melanoma.<h4>Methods</h4>A retrospective study was performed using the National Cancer Database. Patients diagnosed with clinical stage III melanoma were categorized by diagnosis year into two cohorts preceding the advent of novel therapies (P1: 2004-2005, P2: 2008-2009) and a contemporary group (P3: 2012-2013). OS was estimated using standard time-to-event statistical methods.<h4>Results</h4>Of 3720 patients, 525 (14%) were diagnosed in P1, 1375 (37%) in P2, and 1820 (49%) in P3. Median age at diagnosis increased over time (58, 59, and 61 years in P1, P2, and P3, respectively, P = 0.004). OS increased between P2 (median 49.3 months) and P3 (median 58.2 months, Bonferroni-corrected log-rank P < 0.001) but did not differ between P1 (median 50.5 months) and P2 (Bonferroni-corrected log-rank P > 0.99). These differences persisted on multivariable analysis. OS improved for patients diagnosed in P3 compared with P1 [hazard ratio (HR) 0.76, P < 0.001] but not P2 compared with P1 (HR 0.96, P = 0.52).<h4>Conclusions</h4>OS has significantly improved nationally for patients newly diagnosed with clinical stage III melanoma in the era of novel melanoma therapies. OS outcomes will likely continue to evolve as these agents are increasingly utilized in the adjuvant setting. These data may help to better inform affected patients with respect to prognosis.
Project description:The most feared complication following intestinal resection is anastomotic leakage. In high risk areas (esophagus/rectum) where neoadjuvant chemoradiation is used, the incidence of anastomotic leaks remains unacceptably high (? 10%) even when performed by specialist surgeons in high volume centers. The aims of this study were to test the hypothesis that anastomotic leakage develops when pathogens colonizing anastomotic sites become in vivo transformed to express a tissue destroying phenotype. We developed a novel model of anastomotic leak in which rats were exposed to pre-operative radiation as in cancer surgery, underwent distal colon resection and then were intestinally inoculated with Pseudomonas aeruginosa, a common colonizer of the radiated intestine. Results demonstrated that intestinal tissues exposed to preoperative radiation developed a significant incidence of anastomotic leak (>60%; p<0.01) when colonized by P. aeruginosa compared to radiated tissues alone (0%). Phenotype analysis comparing the original inoculating strain (MPAO1- termed P1) and the strain retrieved from leaking anastomotic tissues (termed P2) demonstrated that P2 was altered in pyocyanin production and displayed enhanced collagenase activity, high swarming motility, and a destructive phenotype against cultured intestinal epithelial cells (i.e. apoptosis, barrier function, cytolysis). Comparative genotype analysis between P1 and P2 revealed a single nucleotide polymorphism (SNP) mutation in the mexT gene that led to a stop codon resulting in a non-functional truncated protein. Replacement of the mutated mexT gene in P2 with mexT from the original parental strain P1 led to reversion of P2 to the P1 phenotype. No spontaneous transformation was detected during 20 passages in TSB media. Use of a novel virulence suppressing compound PEG/Pi prevented P. aeruginosa transformation to the tissue destructive phenotype and prevented anastomotic leak in rats. This work demonstrates that in vivo transformation of microbial pathogens to a tissue destroying phenotype may have important implications in the pathogenesis of anastomotic leak.
Project description:To better understand the effects of COVID-19 on air quality in Taiyuan, hourly in situ measurements of PM<sub>2.5</sub>(particulate matter with an aerodynamic diameter less than 2.5 mm) and chemical components (water-soluble ions, organic carbon (OC), elemental carbon (EC), and trace elements) were conducted before (P1: 1 January-23 January 2020) and during (P2: 24 January-15 February 2020) the coronavirus disease 2019 (COVID-19) outbreak. The average concentrations of PM<sub>2.5</sub> dropped from 122.0 μg/m<sup>3</sup> during P1 to 83.3 μg/m<sup>3</sup> during P2. Compared with P1, except for fireworks burning-related chemical components (K<sup>+</sup>, Mg<sup>2+</sup>, K, Cu, Ba), the concentrations of other chemical components of PM<sub>2.5</sub> decreased by14.9-69.8%. Although the large decrease of some emission sources, fireworks burning still resulted in the occurrence of pollution events during P2. The analysis results of positive matrix factorization model suggested that six PM<sub>2.5</sub> sources changed significantly before and during the outbreak of the epidemic. The contributions of vehicle emission, industrial process, and dust to PM<sub>2.5</sub> decreased from 23.1%, 3.5%, and 4.0% during P1 to 7.7%, 3.4%, and 2.3% during P2, respectively, whereas the contributions of secondary inorganic aerosol, fireworks burning, and coal combustion to PM<sub>2.5</sub> increased from 62.0%, 1.8%, and 5.5% to 71.5%, 9.0%, and 6.2%, respectively. The source apportionment results were also affected by air mass transport. The largest reductions of vehicle emission, industrial process, and dust source were distinctly seen for the air masses from northwest.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1007/s11869-021-01082-y.
Project description:The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher's exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.
Project description:The ribosomal stalk is formed by four acidic phosphoproteins in Saccharomyces cerevisiae, P1?, P1?, P2? and P2?, which form two heterodimers, P1?/P2? and P1?/P2?, that preferentially bind to sites A and B of the P0 protein, respectively. Using mutant strains carrying only one of the four possible P1/P2 combinations, we found a specific phenotype associated to each P1/P2 pair, indicating that not all acidic P proteins play the same role. The absence of one P1/P2 heterodimer reduced the rate of cell growth by varying degrees, depending on the proteins missing. Synthesis of the 60S ribosomal subunit also decreased, particularly in strains carrying the unusual P1?-P2? or P1?-P2? heterodimers, although the distinct P1/P2 dimers are bound with similar affinity to the mutant ribosome. While in wild-type strains the B site bound P1?/P2? in a highly specific manner and the A site bound the four P proteins similarly, both the A and B binding sites efficiently bound practically any P1/P2 pair in mutant strains expressing truncated P0 proteins. The reported results support that while most ribosomes contain a P1?/P2?-P0-P1?/P2? structure in normal conditions, the stalk assembly mechanism can generate alternative compositions, which have been previously detected in the cell.