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Introduction: Clinical research coordinators (CRCs) play a key role in supporting the translational research enterprise, with responsibilities encompassing tasks related to the design, implementation, and evaluation of clinical research trials. While the literature explores CRC competencies, job satisfaction, and retention, little attention has been given to the role of the PI working with Human Resources (HR) in the CRC hiring and onboarding processes. We investigated the priorities, decision-making processes, and satisfaction levels of principal investigators (PIs) and hiring managers in CRC hiring. Methods: An online survey consisting of open-ended and fixed-choice questions to gather information on desired CRC qualifications and competencies, factors influencing hiring decisions, and overall satisfaction with selected candidates was administered. The survey utilized a Task/Competency Checklist developed from job descriptions and the literature. Respondents were asked to rank the importance of factors such as CRC skill set, years of experience, educational background, and budget constraints. Results: Results indicated that the skill set of the applicant was the most frequently cited factor influencing the hiring decision, followed by years of experience. Education and budget constraints were of lesser importance. Most respondents reported a satisfaction rating of 50% or greater with their new hires, although some participants expressed challenges related to institutional training requirements, the performance of entry-level CRCs, and the qualifications of experienced candidates. Conclusion: The hiring cycle involves HR-PI collaboration for a clear job description, effective onboarding processes, and accessible professional development opportunities to enhance PI and employee satisfaction and CRC retention.
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Few studies have considered whether hidden (asymptomatic) plant pathogen infection alters ecological interactions at the higher trophic levels, even though such infection still affects plant physiology. We explored this question in two field experiments, where two varieties of lettuce (Little Gem, Tom Thumb) infected with Botrytis cinerea were either (1) naturally colonised by aphids or (2) placed in the field with an established aphid colony. We then recorded plant traits and the numbers and species of aphids, their predators, parasitoids and hyperparasitoids. Infection significantly affected plant quality. In the first experiment, symptomatically infected plants had the fewest aphids and natural enemies of aphids. The diversity and abundance of aphids did not differ between asymptomatically infected and uninfected Little Gem plants, but infection affected the aphid assemblage for Tom Thumb plants. Aphids on asymptomatically infected plants were less attractive to predators and parasitoids than those on uninfected plants, while hyperparasitoids were not affected. In the second experiment, when we excluded natural enemies, aphid numbers were lower on asymptomatically and symptomatically infected plants, but when aphid natural enemies were present, this difference was removed, most likely because aphids on uninfected plants attracted more insect natural enemies. This suggests that hidden pathogen infection may have important consequences for multitrophic interactions.
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Preferred interests are characteristic of autism spectrum disorder and are reported by parents starting at an early age. However, limited research has explored the presentation of preferred interests in toddlerhood. Previous literature suggests that both the intensity and type of preferred interests held by autistic individuals differ from those held by peers with developmental delay and no diagnosis and that autistic interests are more unusual in nature. While preferred interests are seen in typical child development, previous research suggests that the presence of preferred interests in children with no diagnosis declines with age. Literature also indicates that the sex and cognitive ability of autistic children influences preferred interests. Identification of early preferred interests commonly held by autistic toddlers could serve as a useful clinical indicator of future diagnosis. This article explored whether diagnostic group, age, sex, and cognitive ability predict the likelihood that parents reported preferred interests in children aged 12-36 months with diagnoses of autism, developmental delay, and those with no diagnosis. Additionally, we explored potential diagnostic group differences in interest type. Results suggest that diagnostic group, but not age, sex, or cognitive ability, predicts the likelihood that parents report preferred interests. No differences in the type of interests among diagnostic groups were identified. These results support the use of preferred interests as an early sign of autism but suggest that interest type may not be a helpful clinical indicator of autism in toddlerhood.
Subject(s)
Autism Spectrum Disorder , Humans , Child, Preschool , Male , Female , Infant , Autism Spectrum Disorder/diagnosis , Developmental Disabilities/diagnosis , Parents , Autistic Disorder/diagnosisABSTRACT
INTRODUCTION: There is variability in clinical practice regarding the number of radiographic views required to accurately determine umbilical venous catheter (UVC) tip position. Some units prefer performing a single anteroposterior (AP) view and others do both AP and lateral views. The aim of this study was to compare the need for one versus two radiographical views to accurately determine UVC tip position. METHODS: Radiographs of 382 infants (all gestations) from two level six neonatal units were included in the study. Patients with congenital anomalies and those who had adjustment of UVC position between AP and lateral films being performed were excluded. Six clinicians reviewed anonymized AP only images and documented UVC tip position. Subsequently, they reviewed both AP and lateral views and again documented the UVC tip position. Results were compared to the expert consensus which was taken from the consensus of two paediatric radiologists. RESULTS: The study population had a mean gestational age of 32.8 weeks and birth weight of 2190 g, with 58% males. The UVC tip positions were accurately determined 76% times by the AP view alone and 82% times by using both the AP and lateral views (P < 0.001). The low placed UVC tip position which is the most inappropriate for use was more accurately determined by two images (78% times) rather than single image (70% times) (P < 0.001). CONCLUSIONS: Utilising both AP and lateral views was superior in accurately determining UVC tip position to AP view alone.
Subject(s)
Umbilical Veins , Humans , Infant, Newborn , Retrospective Studies , Umbilical Veins/diagnostic imaging , Male , FemaleABSTRACT
Introduction: Purposeful training and ongoing career support are necessary to meet the evolving and expanding roles of clinical research professionals (CRP). To address the training and employment needs of clinical research coordinators (CRCs), one of the largest sectors of the CRP workforce, we designed, developed, and implemented an online career navigation system, eMPACTTM (eMpowering Purposeful Advancement of Careers and Training). Methods: A design-based research method was employed as an overarching approach that frames iterative design, development, and implementation of educational interventions. The five major phases of this project - conceptualization, task analysis for measurement development, algorithms development, algorithms validation, and system evaluation - presented specific goals and relevant methods. Results: The results reported how the eMPACTTM system was conceptualized, developed, and validated. The system allowed CRCs to navigate tailored training and job opportunities by completing their task competencies and career goals. The data sets could, in turn, support employees' and training coordinators' informed decisions about organizational training needs and recruitment. The early dissemination results showed steady growth in registered CRCs and diversity in users' ethnicity and job levels. Conclusions: The eMPACTTM service showed the possibility of supporting CRCs' individual career advancement and organizational workforce enhancement and diversity. Long-term research is needed to evaluate its impact on CRC workforce development, explore key factors influencing workforce sustainability, and expand eMPACTTM service to other CRP sectors.
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Clinicians form initial impressions about a child's diagnosis based on behavioral features, but research has not yet identified specific behaviors to guide initial diagnostic impressions. Participants were toddlers (N = 55, mean age 22.9 months) from a multi-site early detection study, referred for concern for ASD due to screening or parent/provider concern. Within 5 min of meeting a child, clinicians noted ASD or non-ASD impression, confidence in impression, and behaviors that informed their impression. These clinicians also determined final diagnoses for each child. When a child's final diagnosis was ASD (n = 35), senior clinicians formed an initial impression of ASD in 22 cases (63%) but missed 13 cases (37%). When final diagnosis was non-ASD (n = 20), senior clinicians made an initial impression of non-ASD in all cases (100%). Results were similar among junior clinicians. Senior and junior clinicians used the same behaviors to form accurate impressions of ASD and non-ASD: social reciprocity, nonverbal communication, and eye contact. Senior clinicians additionally used focus of attention when forming accurate impressions of ASD and non-ASD; junior clinicians used this behavior only when forming accurate non-ASD impressions. Clinicians' initial impressions of ASD are very likely to be consistent with final diagnoses, but initial impressions of non-ASD need follow-up. Toddlers who show all four atypical behaviors (social reciprocity, nonverbal communication, eye contact, and focus of attention) might receive expedited ASD diagnoses. However, presence of apparently typical behaviors should not rule out ASD; for some children a longer evaluation is necessary to allow for more opportunities to observe subtle social behavior.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child Development Disorders, Pervasive , Humans , Child, Preschool , Child , Infant , Autistic Disorder/diagnosis , Autism Spectrum Disorder/diagnosis , Child Development Disorders, Pervasive/diagnosis , Social Behavior , Mental ProcessesABSTRACT
The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of [Formula: see text] patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological cancers at risk of being subtracted by standard variant calling pipelines. Our work highlights the importance of contamination assessment for accurate somatic variants detection in research and clinical settings, especially with large-scale sequencing projects being utilised to deliver accurate data from which to make clinical decisions for patient care.
Subject(s)
Neoplasms , Whole Genome Sequencing , Humans , Genomics , Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/genetics , Mutation , Neoplasms/diagnosis , Neoplasms/genetics , Neoplasms/pathologyABSTRACT
ABSTRACT: CD19-negative relapse is a leading cause of treatment failure after chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral cotransduction with vectors encoding our previously described fast-off rate CD19 CAR (AUTO1) combined with a novel CD22 CAR capable of effective signaling at low antigen density. Twelve patients with advanced B-cell acute lymphoblastic leukemia were treated (CARPALL [Immunotherapy with CD19/22 CAR Redirected T Cells for High Risk/Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia] study, NCT02443831), a third of whom had failed prior licensed CAR therapy. Toxicity was similar to that of AUTO1 alone, with no cases of severe cytokine release syndrome. Of 12 patients, 10 (83%) achieved a measurable residual disease (MRD)-negative complete remission at 2 months after infusion. Of 10 responding patients, 5 had emergence of MRD (n = 2) or relapse (n = 3) with CD19- and CD22-expressing disease associated with loss of CAR T-cell persistence. With a median follow-up of 8.7 months, there were no cases of relapse due to antigen-negative escape. Overall survival was 75% (95% confidence interval [CI], 41%-91%) at 6 and 12 months. The 6- and 12-month event-free survival rates were 75% (95% CI, 41%-91%) and 60% (95% CI, 23%-84%), respectively. These data suggest dual targeting with cotransduction may prevent antigen-negative relapse after CAR T-cell therapy.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Humans , Child , Immunotherapy, Adoptive , Receptors, Chimeric Antigen/genetics , Recurrence , Antigens, CD19 , T-Lymphocytes , Sialic Acid Binding Ig-like Lectin 2ABSTRACT
BACKGROUND: Type 2 diabetes is a public health priority for the UK. A growing body of evidence has indicated ethnic and socioeconomic disparities in rates of diabetes prevalence and complications. Attendance at diabetes follow-up checks is key to ensuring complications are identified and managed at an early stage. The aim of this rapid review was to identify and summarise evidence of ways to improve diabetes management in ethnic minority groups. METHODS: In this rapid review, we searched PubMed, PsycInfo, and CINAHL for studies published in English between Jan 1, 2000, and Jan 31, 2023. Studies were included if the population was from ethnic minority groups and if the intervention was community-based and aimed to improve diabetes self-care. The comparisons were persuasion and behaviour change, and the outcomes were improved diabetes self-management including, glycaemic control, attending eye tests, kidney, and foot screening follow-up checks. This study is registered with PROSPERO 2023, CRD42023399283. FINDINGS: Nine studies were included, from Mexico (n=1), USA (n=7), and UK (n=1). Most studies reported on community engagement (n=8), and one focussed on peer support and diabetes self-management. Peer support and diabetes self-management education were found to significantly improve diabetes control in a Mayan community (n=29) in Mexico (p<0·0001) and in the Korean American (n=105), African American (n=107), and Latino American (n=56) communities in the USA. Another study showed that women from the Pakistani community in England also benefitted from a culturally appropriate and socially supportive environment when learning about diabetes self-management. Diabetic eye screening rates could be increased through education but not through incentive payments. INTERPRETATION: Culturally competent health-care policies and programmes have been shown to increase diabetes self-management including uptake of diabetes screening for people with diabetes from ethnic minority communities to avoid potential harmful and life limiting conditions. A strength of this review is that robust, recent, and relevant papers regarding self-management of diabetes were included. The main limitations were that none of the nine studies included any cost analyses, and only one UK-based study was included, indicating that further research is required to fill the evidence gap. FUNDING: Research for Patient and Public Benefit (RfPPB), Health and Care Research Wales.
Subject(s)
Diabetes Mellitus, Type 2 , Minority Groups , Humans , Female , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Ethnicity , Follow-Up Studies , Health BehaviorABSTRACT
Background: Low-risk and realistic simulation strategies are needed to train clinical learners to perform hands-on invasive procedures. This follow-up study compares the utility of landmark-guided palpation-based to ultrasound-guided teaching techniques for subclavian central venous access using formalin-embalmed cadavers. Methods: The subclavian veins of 3 cadavers were imaged with ultrasound to evaluate vein patency before palpation-based venous access was attempted. Twenty-three first-year medical students were trained to access the subclavian vein using palpation-based techniques. Training involved ten minutes of didactic orientation and ten minutes of hands-on practical instruction using cadavers. Participant confidence was measured using a 10-point Likert scale on pre- and post-training questionnaires. Objective skills testing for each participant included quantifying the number of skin punctures and recording the time elapsed from first skin puncture to fluid flashback into the syringe. Data was analyzed using a generalized linear model (GLM) approach. Results: Participant confidence significantly increased following training in both ultrasound and palpation training groups across all questionnaire items (P<0.001). The ultrasound group had fewer skin punctures (P<0.001) and fewer failures (1) than the palpation group (6). Participants in the ultrasound group were more confident than those in the palpation group in their ability to locate the vein and select the optimal site for needle access (P<0.05). Conclusion: Formalin-embalmed cadavers provide a safe, stress-free, and effective means by which to train students in subclavian vein access using both palpation and ultrasound-based techniques. Repeated practice accessing and aspirating fluid from a cadaveric subclavian vein significantly increases trainee confidence, an essential factor in physician performance that may lead to fewer complications. Introducing this type of low-risk and hands-on practice may be beneficial for trainees before they attempt subclavian vein access on live patients.
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PURPOSE: Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care. METHODS: A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds. RESULTS: We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision. CONCLUSIONS: We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.
Subject(s)
COVID-19 , Neoplasms , Humans , Analgesics, Opioid/therapeutic use , Pandemics , Wales/epidemiology , Retrospective Studies , Analgesics , Neoplasms/epidemiology , Death , PrescriptionsSubject(s)
Antineoplastic Agents , Appendiceal Neoplasms , Colorectal Neoplasms , Peritoneal Neoplasms , Humans , United States , Oxaliplatin/therapeutic use , Appendiceal Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , AerosolsABSTRACT
Mucinous neoplasms are commonly seen in the ovaries and pancreas. Their occurrence in the retroperitoneum is uncommon. We present a case of a retroperitoneal mucinous cystadenocarcinoma in a 54-year-old female who presented with right flank pain. Imaging demonstrated an 8.6 × 7.9 cm mass at the anterior surface of the lower pole of the right kidney, suspicious for renal cell carcinoma. Serum tumor markers carbohydrate antigen 19-9 (CA 19-9) and cancer embryonic antigen (CEA) were within normal limits, and cancer antigen 125 (CA 125) was elevated. Surgical resection of the mass was performed. Intraoperatively, the mass was noted to lie in the retroperitoneum, unattached to the kidney. On gross examination, a 10.0 × 7.0 × 7.0 cm unilocular cystic structure with red-brown mucoid material was present. The inner lining was mostly smooth with areas of excrescences, covering less than 5% of the surface area. Microscopic examination showed cystic areas lined by mucinous epithelium with an underlying ovarian-type stroma. Solid areas showed features of a borderline papillary mucinous tumor with invasive carcinoma. A diagnosis of mucinous cystadenocarcinoma was made. Their occurrence in the retroperitoneum is unusual. Although rare, this entity should always be considered in the differential diagnosis of retroperitoneal cystic lesions.
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BACKGROUND: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a laparoscopic locoregional treatment for peritoneal metastases (PM) from colorectal cancer (CRC) or appendiceal cancer (AC) in patients who cannot undergo cytoreductive surgery (CRS). While PIPAC has been studied in Europe and Asia, it has not been investigated in the USA. PATIENTS AND METHODS: We evaluated PIPAC with 90 mg/m2 oxaliplatin alone (cycle 1) and preceded by systemic chemotherapy with fluorouracil (5-FU) and leucovorin (LV) (cycle 2-3) as a multicenter prospective phase I clinical trial (NCT04329494). The primary endpoint was treatment-related adverse events (AEs). Secondary endpoints included survival and laparoscopic, histologic, and radiographic response. RESULTS: 12 patients were included: 8 with CRC and 4 with AC. Median prior chemotherapy cycles was 2 (interquartile range (IQR) 2-3). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median peritoneal carcinomatosis index (PCI) was 28 (IQR 19-32). Six (50%) of twelve patients completed three PIPAC cycles. No surgical complications or dose-limiting toxicities were observed. Two patients developed grade 3 treatment-related toxicities (one abdominal pain and one anemia). Median overall survival (OS) was 12.0 months, and median progression-free survival (PFS) was 2.9 months. OS was correlated with stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but not with laparoscopic response by PCI or histologic response by peritoneal regression grading system (PRGS). CONCLUSIONS: This phase I trial in the USA demonstrated safety, feasibility, and early efficacy signal of PIPAC with oxaliplatin and chemotherapy in patients with PM from AC or CRC who are refractory to standard lines of systemic chemotherapy.
Subject(s)
Appendiceal Neoplasms , Colorectal Neoplasms , Peritoneal Neoplasms , Humans , Oxaliplatin , Appendiceal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Prospective Studies , Aerosols , Fluorouracil/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathologyABSTRACT
Background: Long COVID occurs in those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whose symptoms persist or develop beyond the acute phase. We conducted a systematic review to determine the prevalence of persistent symptoms, functional disability, or pathological changes in adults or children at least 12 weeks postinfection. Methods: We searched key registers and databases from January 1, 2020 to November 2, 2021, limited to publications in English and studies with at least 100 participants. Studies in which all participants were critically ill were excluded. Long COVID was extracted as prevalence of at least 1 symptom or pathology, or prevalence of the most common symptom or pathology, at 12 weeks or later. Heterogeneity was quantified in absolute terms and as a proportion of total variation and explored across predefined subgroups (PROSPERO ID CRD42020218351). Results: One hundred twenty studies in 130 publications were included. Length of follow-up varied between 12 weeks and 12 months. Few studies had low risk of bias. All complete and subgroup analyses except 1 had I2 ≥90%, with prevalence of persistent symptoms range of 0%-93% (pooled estimate [PE], 42.1%; 95% prediction interval [PI], 6.8% to 87.9%). Studies using routine healthcare records tended to report lower prevalence (PE, 13.6%; PI, 1.2% to 68%) of persistent symptoms/pathology than self-report (PE, 43.9%; PI, 8.2% to 87.2%). However, studies systematically investigating pathology in all participants at follow up tended to report the highest estimates of all 3 (PE, 51.7%; PI, 12.3% to 89.1%). Studies of hospitalized cases had generally higher estimates than community-based studies. Conclusions: The way in which Long COVID is defined and measured affects prevalence estimation. Given the widespread nature of SARS-CoV-2 infection globally, the burden of chronic illness is likely to be substantial even using the most conservative estimates.
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INTRODUCTION AND IMPORTANCE: Intraoperative cholangiogram has always been a critical procedure that allows identification of biliary anatomy, thereby reducing the risks of bile duct injuries. CASE PRESENTATION: We present a unique case where the intraoperative cholangiogram highlighted a suspected duodenal injury. CLINICAL DISCUSSION: This case discusses the intraoperative steps taken to ensure there was no injury, highlight the importance of cholangiogram interpretation as a skill for all surgeons. CONCLUSION: Intraoperative cholangiogram is a crucial procedure to highlight both biliary and non-biliary anatomy and can be used to identify duodenal injuries as was assessed in our case.
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BACKGROUND: Cytidine deamination that is guided by clustered regularly interspaced short palindromic repeats (CRISPR) can mediate a highly precise conversion of one nucleotide into another - specifically, cytosine to thymine - without generating breaks in DNA. Thus, genes can be base-edited and rendered inactive without inducing translocations and other chromosomal aberrations. The use of this technique in patients with relapsed childhood T-cell leukemia is being investigated. METHODS: We used base editing to generate universal, off-the-shelf chimeric antigen receptor (CAR) T cells. Healthy volunteer donor T cells were transduced with the use of a lentivirus to express a CAR with specificity for CD7 (CAR7), a protein that is expressed in T-cell acute lymphoblastic leukemia (ALL). We then used base editing to inactivate three genes encoding CD52 and CD7 receptors and the ß chain of the αß T-cell receptor to evade lymphodepleting serotherapy, CAR7 T-cell fratricide, and graft-versus-host disease, respectively. We investigated the safety of these edited cells in three children with relapsed leukemia. RESULTS: The first patient, a 13-year-old girl who had relapsed T-cell ALL after allogeneic stem-cell transplantation, had molecular remission within 28 days after infusion of a single dose of base-edited CAR7 (BE-CAR7). She then received a reduced-intensity (nonmyeloablative) allogeneic stem-cell transplant from her original donor, with successful immunologic reconstitution and ongoing leukemic remission. BE-CAR7 cells from the same bank showed potent activity in two other patients, and although fatal fungal complications developed in one patient, the other patient underwent allogeneic stem-cell transplantation while in remission. Serious adverse events included cytokine release syndrome, multilineage cytopenia, and opportunistic infections. CONCLUSIONS: The interim results of this phase 1 study support further investigation of base-edited T cells for patients with relapsed leukemia and indicate the anticipated risks of immunotherapy-related complications. (Funded by the Medical Research Council and others; ISRCTN number, ISRCTN15323014.).
Subject(s)
Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adolescent , Child , Female , Humans , Antigens, CD19 , Antigens, CD7 , CD52 Antigen , Hematopoietic Stem Cell Transplantation/adverse effects , Immunotherapy, Adoptive/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Receptors, Antigen, T-Cell/genetics , Recurrence , Stem Cell Transplantation , T-LymphocytesABSTRACT
AIMS: To assess if the risk of all-cause mortality increases in people with type 1 diabetes (T1D) with increasing number of severe hypoglycaemia episodes requiring hospitalization. MATERIALS AND METHODS: We conducted a national retrospective observational cohort study in people with T1D (diagnosed between 2000 and 2018). Clinical, comorbidity and demographic variables were assessed for impact on mortality for people with no, one, two and three or more episodes of severe hypoglycaemia requiring hospitalization. The time to death (all-cause mortality) from the timepoint of the last episode of severe hypoglycaemia was modelled using a parametric survival model. RESULTS: A total of 8224 people had a T1D diagnosis in Wales during the study period. The mortality rate (95% confidence interval [CI]) was 6.9 (6.1-7.8) deaths/ 1000 person-years (crude) and 15.31 (13.3-17.63) deaths/ 1000 person-years (age-adjusted) for those with no occurrence of severe hypoglycaemia requiring hospitalization. For those with one episode of severe hypoglycaemia requiring hospitalization the mortality rate (95% CI) was 24.9 (21.0-29.6; crude) and 53.8 (44.6-64.7) deaths/ 1000 person-years (age-adjusted), for those with two episodes of severe hypoglycaemia requiring hospitalization it was 28.0 (23.1-34.0; crude) and 72.8 (59.2-89.5) deaths/ 1000 person-years (age-adjusted), and for those with three or more episodes of severe hypoglycaemia requiring hospitalization it was 33.5 (30.0-37.3; crude) and 86.3 (71.7-103.9) deaths/ 1000 person years (age-adjusted; P < 0.001). A parametric survival model showed that having two episodes of severe hypoglycaemia requiring hospitalization was the strongest predictor for time to death (accelerated failure time coefficient 0.073 [95% CI 0.009-0.565]), followed by having one episode of severe hypoglycaemia requiring hospitalization (0.126 [0.036-0.438]) and age at most recent episode of severe hypoglycaemia requiring hospitalization (0.917 [0.885-0.951]). CONCLUSIONS: The strongest predictor for time to death was having two or more episodes of severe hypoglycaemia requiring hospitalization.
Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Humans , Diabetes Mellitus, Type 1/complications , Hypoglycemic Agents/therapeutic use , Retrospective Studies , Hypoglycemia/epidemiology , HospitalizationABSTRACT
Reducing the age of first autism diagnosis facilitates access to critical early intervention services. A current "waitlist crisis" for autism diagnostic evaluation thus demands that we consider novel use of available clinical resources. Previous work has found that expert autism clinicians can identify autism in young children with high specificity after only a brief observation; rapid identification by non-experts remains untested. In the current study, 252 children ages 12-53 months presented for a comprehensive autism diagnostic evaluation. We found that junior clinicians in training to become autism specialists (n = 29) accurately determined whether or not a young child would be diagnosed with autism in the first five minutes of the clinic visit in 75% of cases. Specificity of brief observations was high (0.92), suggesting that brief observations may be an effective tool for triaging young children toward autism-specific interventions. In contrast, the lower negative predictive value (0.71) of brief observations, suggest that they should not be used to rule out autism. When trainees expressed more confidence in their initial impression, their impression was more likely to match the final diagnosis. These findings add to a body of literature showing that clinical observations of suspected autism should be taken seriously, but lack of clinician concern should not be used to rule out autism or overrule other indicators of likely autism, such as parent concern or a positive screening result.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Humans , Child, Preschool , Autistic Disorder/diagnosis , Autism Spectrum Disorder/diagnosis , Predictive Value of Tests , Parents , Early Intervention, Educational , Sensitivity and SpecificityABSTRACT
INTRODUCTION AND IMPORTANCE: Bouveret syndrome is a rare type of gallstone ileus causing gastric outlet obstruction with high morbidity and mortality risk, and hence important to have a high degree of clinical suspicion on presentation for prompt diagnosis and management. CASE PRESENTATION: We present a case of an elderly woman with abdominal pain, haematemesis, and an unremarkable radiograph whose initial emergent endoscopy showed a gastric obstruction and a duodenal diverticulum with a non-bleeding broad based duodenal ulcer. Subsequent computerised tomographic (CT) scan revealed a cholecystoduodenal fistula and gastric outlet obstruction secondary to a 5 cm stone in the duodenojejunal (DJ) flexure. A repeat endoscopy was attempted for endoscopic removal prior to proceeding to open enterolithotomy. CLINICAL DISCUSSION: This case highlights the challenges in diagnosis and discusses the latest literature on multimodal management consisting of endoscopy and surgery. CONCLUSION: The location of the obstructing stone at the duodenojejunal flexure is extremely rare and therefore will add to world literature on Bouveret syndrome.