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61.
6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT1513 and NUDT1512 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT1513 and NUDT1512, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients. 相似文献
62.
《Patient education and counseling》2022,105(7):2005-2011
ContextHuman connection can reduce suffering and facilitate meaningful decision-making amid the often terrifying experience of hospitalization for advanced cancer. Some conversational pauses indicate human connection, but we know little about their prevalence, distribution or association with outcomes.PurposeTo describe the epidemiology of Connectional Silence during serious illness conversations in advanced cancer.MethodsWe audio-recorded 226 inpatient palliative care consultations at two academic centers. We identified pauses lasting 2+ seconds and distinguished Connectional Silences from other pauses, sub-categorized as either Invitational (ICS) or Emotional (ECS). We identified treatment decisional status pre-consultation from medical records and post-consultation via clinicians. Patients self-reported quality-of-life before and one day after consultation.ResultsAmong all 6769 two-second silences, we observed 328 (4.8%) ECS and 240 (3.5%) ICS. ECS prevalence was associated with decisions favoring fewer disease-focused treatments (ORadj: 2.12; 95% CI: 1.12, 4.06). Earlier conversational ECS was associated with improved quality-of-life (p = 0.01). ICS prevalence was associated with clinicians' prognosis expectations.ConclusionsConnectional Silences during specialist serious illness conversations are associated with decision-making and improved patient quality-of-life. Further work is necessary to evaluate potential causal relationships.Practice implicationsPauses offer important opportunities to advance the science of human connection in serious illness decision-making. 相似文献
63.
Posttraumatic stress disorder (PTSD) is a highly prevalent, debilitating mental health condition. A better understanding of contributory neurobiological mechanisms will lead to effective treatments, improving quality of life for patients. Given that not all trauma-exposed individuals develop PTSD, identification of pre-trauma susceptibility factors that can modulate posttraumatic outcomes is important. Recent clinical evidence supports a strong link between inflammatory conditions and PTSD. A particularly strong association has been reported between asthma and PTSD prevalence and severity. Unlike many other PTSD-comorbid inflammatory conditions, asthma often develops in children, sensitizing them to subsequent posttraumatic pathology throughout their lifetime. Currently, there is a significant need to understand the neurobiology, shared mechanisms, and inflammatory mediators that may contribute to comorbid asthma and PTSD. Here, we provide a translational perspective of asthma and PTSD risk and comorbidity, focusing on clinical associations, relevant rodent paradigms and potential mechanisms that may translate asthma-associated inflammation to PTSD development. 相似文献
64.
65.
《Genetics in medicine》2019,21(3):545-552
PurposeCongenital microcephaly (CM) is an important birth defect with long term neurological sequelae. We aimed to perform detailed phenotypic and genomic analysis of patients with Mendelian forms of CM.MethodsClinical phenotyping, targeted or exome sequencing, and autozygome analysis.ResultsWe describe 150 patients (104 families) with 56 Mendelian forms of CM. Our data show little overlap with the genetic causes of postnatal microcephaly. We also show that a broad definition of primary microcephaly —as an autosomal recessive form of nonsyndromic CM with severe postnatal deceleration of occipitofrontal circumference—is highly sensitive but has a limited specificity. In addition, we expand the overlap between primary microcephaly and microcephalic primordial dwarfism both clinically (short stature in >52% of patients with primary microcephaly) and molecularly (e.g., we report the first instance of CEP135-related microcephalic primordial dwarfism). We expand the allelic and locus heterogeneity of CM by reporting 37 novel likely disease-causing variants in 27 disease genes, confirming the candidacy of ANKLE2, YARS, FRMD4A, and THG1L, and proposing the candidacy of BPTF, MAP1B, CCNH, and PPFIBP1.ConclusionOur study refines the phenotype of CM, expands its genetics heterogeneity, and informs the workup of children born with this developmental brain defect. 相似文献
66.
《The American journal of emergency medicine》2019,37(9):1633-1642
Emergency Medical Services (EMS) are acute services provided outside of the hospital. EMS are crucial in rural environments where hospitals are often far away and difficult to access. Establishing EMS performance measures is critical in improving a rural community's access to these services and eliminating systemic inequalities. However, an absence of data leads to challenges in developing objective and quantifiable service metrics. EMS data are regularly collected through the National EMS Information System (NEMSIS), yet the manner of data collection and quality of data vary across agencies. Moreover, the amount and complexity of information makes data analyses difficult, subsequently effecting EMS leaderships' ability to identify improvement needs.This study used NEMSIS data to exemplify approaches for establishing two data-driven performance measures. The measures used in this study – timely service and service coverage – are both dependent on the mobility and accessibility of the EMS transportation network. Two types of spatial models: the spatial econometric model and geographically weighted regression (GWR) model, were developed and then compared to the linear regression model to help identify response time factors. GWR performed best in terms of goodness-of-fit statistics and was chosen to help understand how factors (e.g., weather, transportation) impact the timely provision of EMS in rural areas. The GWR results provided additional insights through the particular spatial patterns of the coefficient estimates and their statistical significance to EMS practitioner for their references to reduce local response times. 相似文献
67.
68.
《HPB : the official journal of the International Hepato Pancreato Biliary Association》2022,24(8):1291-1304
BackgroundWe aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments.MethodsData were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments).Results2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS.ConclusionSH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented. 相似文献
69.
《Patient education and counseling》2022,105(5):1224-1228
ObjectiveVaccine hesitancy is a persistent barrier to vaccination uptake, and health professionals report interactions with such parents to be difficult. Using discourse analytic techniques, we examine the foundation of a therapeutic relationship: the display of empathy and attempts to build rapport, in consultations between immunisation specialists and vaccine reluctant parents.MethodsConsultations between consenting clinicians and parents in two Specialist Immunisation Clinics in Australia were recorded. Twelve conversations between the clinicians and parents were analysed using interactional sociolinguistic (IS) discourse analytic methods.ResultsThis paper takes a case study approach by citing two interactions that exemplify the interactional work of the consultants as they strive to engender mutual understanding and goodwill, noting examples of discursive choices that demonstrate empathy and the building of rapport.ConclusionAwareness of discourse strategies that interweave relational and clinical goals enable a more nuanced understanding of communication skills that support a guiding partnership in vaccine related decisions with parents.Practical implicationsThrough highlighting the strategic interactional work that displays empathy and builds rapport, we can inform educational approaches and build a repertoire of communication choices that strengthen the communication skills of health professionals. 相似文献
70.
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and transmitted by triatomine insect vectors. In Guatemala, insecticide spraying is an integral part of management of the main vector, Triatoma dimidiata. Spraying typically has low efficacy, which may be due to incomplete elimination from infested houses, within-village dispersal, or influx from other villages or sylvan environments. To evaluate how these mechanisms contribute to reinfestation, we conducted a time-course analysis of T. dimidiata infestation, abundance and household genetic structure in two nearby villages in Jutiapa, Guatemala; houses in the first village were surveyed, treated with insecticide if infested and then re-surveyed at eight and 22 months following spraying, while the second village served as an untreated control to quantify changes associated with seasonal dispersal. Insects were genotyped at 2–3000 SNP loci for kinship and population genetic analyses. Insecticide application reduced overall infestation and abundance, while the untreated village was stable over time. Nevertheless, within two years 35.5% of treated houses were reinfested and genetic diversity had largely recovered. Insects collected from reinfested houses post-spraying were most closely related to pre-spray collections from the same house, suggesting that infestations had not been fully eliminated. Immigration by unrelated insects was also detected within a year of spraying; when it occurred, dispersal was primarily local from neighboring houses. Similar dispersal patterns were observed following the annual dispersal season in the untreated village, with high-infestation houses serving as sources for neighboring homes. Our findings suggest that the efficacy of pyrethroid application is rapidly diminished by both within-house breeding by survivors and annual cycles of among-house movement. Given these patterns, we conclude that house structural improvements, an integral part of the Ecohealth approach that makes houses refractory to vector colonization and persistence, are critical for long-term reduction of T. dimidiata infestation. 相似文献