OBJECTIVE: To develop a list of clinically important drug-drug interactions (DDIs) likely to be encountered in community and ambulatory pharmacy settings and detected by a computerized pharmacy system. DESIGN: Cross-sectional, one-time evaluation. SETTING: United States in fall 2001. PARTICIPANTS: An expert panel comprising two physicians, two clinical pharmacists, and an expert on DDIs. INTERVENTIONS: Systematic review of drug interaction compendia and published literature, ratings (on a 1 to 10 scale) of various clinical aspects of DDIs (e.g., clinical importance, quality and quantity of evidence, causal relationship, risk of morbidity and mortality), and a modified Delphi consensus-building process. MAIN OUTCOME MEASURE: Panelists' opinions about clinical importance of DDIs. RESULTS: The expert panel considered 56 DDIs. Of these, 28 had a mean clinical importance score of 8.0 or more. The ratings for clinical importance ranged from 3.2 to 9.6, with a mean +/- SD of 7.5 +/- 1.5 across the combinations examined. The mean score for the quality of literature suggesting the interaction exists ranged from 1.0 to 9.6, with a mean +/- SD of 5.8 +/- 2.5. In terms of substantiation of the interactions evaluated, the mean +/- SD rating was 6.3 +/- 2.2, with a range from 1.4 to 9.2. Through the modified Delphi process, the panel determined that 25 interactions were clinically important. CONCLUSION: Using an expert panel and a standard evaluation tool, 25 clinically important drug interactions that are likely to occur in the community and ambulatory pharmacy settings were identified. Pharmacists should take steps to prevent patients from receiving these interacting medications, and computer software vendors should focus interaction alerts on these and similarly important DDIs. 相似文献
We detected a highly divergent SARS-CoV-2 Alpha variant in an immunocompromised person several months after the latest detection of the Alpha variant in the Netherlands. The patient was infected for 42 weeks despite several treatment regimens and disappearance of most clinical symptoms. We identified several potential immune escape mutations in the spike protein. 相似文献
Severe posttraumatic stress symptoms (PTSS) are connected to a variety of health-related and interpersonal problems, among them are the insecure attachment orientations. However, psychotherapy seems to improve not only PTSS but also attachment insecurities. In a large multicenter, randomized clinical trial, the attachment characteristics and PTSS of 85 adolescents and young adults (aged 14–21 years) with clinically relevant abuse-related PTSS were assessed at study entry, at the end of treatment, and 3 months after the end of treatment. Participants were randomized either to a developmentally adapted cognitive processing therapy (D-CPT) or to a wait-list with treatment advice (WL/TA). The purpose of the study was to analyze the association between PTSS and attachment at study entry as well as changes in attachment during the trial. We found that attachment-related avoidance (AR avoidance) was positively associated with PTSS from both self-reports and clinician ratings, whereas attachment-related anxiety (AR anxiety) was only related to self-reported PTSS (Pearson correlation coefficients between 0.37 and 0.46). Changes in AR anxiety occurred in both conditions at some point during the study (baseline to 3-month follow-up effect size was d = 0.60 for D-CPT and d = 0.44 for WL/TA) whereas for AR avoidance, only participants in D-CPT improved significantly (baseline to 3-month follow-up effect size was d = 0.75). The results indicate that PTSS and attachment are connected. Positive changes in attachment insecurities brought about by trauma-focused psychotherapy seem possible.
Trial registration: German Clinical Trials Register (DRKS); Germanctr.de; identifier: DRKS00004787; date of registration: 18 March 2013.
The past 50 years have seen great progress in the understanding and treatment of classic growth disorders. Advances such as the recognition of hormone receptor defects, the development of recombinant growth hormone, and the expanding awareness of epigenetic phenomena affecting growth are among these great achievements. Yet growth failure remains a pervasive problem among children with complex health conditions, such as survivors of childhood cancers, premature infants, organ transplant recipients, and children with cystic fibrosis. The significant increases in life expectancy among these groups underscores the potential consequences of poor growth, whether due to the underlying conditions or medical treatments, as they may have long-lasting effects into adulthood. The ongoing contributions of human biologists to the study of human growth remain essential in the recognition and treatment of growth disorders, by defining normal patterns of growth and body composition, the interplay of growth and maturation, the role of environmental, behavioral and genetic factors, and the long-term consequences of growth patterns. Examples will be given based on two common genetic disorders, cystic fibrosis and sickle-cell anemia, to highlight the relationships between growth failure, survival, and malnutrition. Also, a study of bone mineral accretion in children with cystic fibrosis will illustrate the importance of understanding patterns of growth in healthy children, and their application in the diagnosis and management of children with chronic disease. These examples accentuate the need for continued participation of human biologists in the study of growth and development and the care of children. 相似文献
Study ObjectivesOver 75% of US high school students obtain insufficient sleep, placing them at risk for adverse health outcomes. Identification of modifiable determinants of adolescent sleep is needed to inform prevention strategies, yet little is known about the influence of the built environment on adolescent sleep.MethodsIn this prospective study, actigraphy was used to assess sleep outcomes among 110 adolescents for 14 days each in eighth and ninth grades: duration (hours/night), onset and offset, and sleeping ≥8 hours. Home addresses were linked to built environment exposures: sound levels, tree canopy cover, street density, intersection density, population density, and housing density. Mixed-effects regression estimated associations of built environment measures with sleep outcomes, adjusting for sex, race, parent education, household income, household size, grade, weeknight status, and neighborhood poverty.ResultsA 1-standard deviation (SD) increase in neighborhood sound was associated with 16 minutes later sleep onset (β = 0.28; 95% confidence interval (CI): 0.06, 0.49) and 25% lower odds of sleeping for ≥8 hours (odds ratio (OR) = 0.75, 95% CI: 0.59, 0.96). A 1-SD increase in neighborhood tree canopy was associated with 18 minutes earlier sleep onset (β = −0.31, 95% CI: −0.49, −0.13) and 10 minutes earlier sleep offset (β= −0.17, 95% CI: −0.28, −0.05). No associations were observed for density-based exposures.ConclusionsHigher neighborhood sound level was associated with lower odds of sufficient sleep, while higher tree canopy cover was associated with more favorable sleep timing. Neighborhood sound levels and tree canopy cover are potential targets for policies and interventions to support healthier sleep among adolescents. 相似文献
Molecular mechanisms contributing to the tumorigenesis of pancreatic endocrine tumors (PETs) are still not well understood. Allelic deletions at chromosome 22q12.3 were detected in about 30-60% of PETs, suggesting that inactivation of one or more tumor suppressor genes on this chromosomal arm is important for their pathogenesis. Because the putative tumor suppressor gene tissue inhibitor of metalloproteinase-3 (TIMP-3) has been located at 22q12.3, we undertook a genetic analysis of TIMP-3 to determine its role in the tumorigenesis of PETs. Single-strand conformational polymorphism analysis, methylation-specific PCR, RNA expression analysis, and immunohistochemistry of TIMP-3 were performed in 21 sporadic PETs. Thirteen of 21 PETs (62%) revealed TIMP-3 alterations, including promoter hypermethylation and homozygous deletion. The predominant TIMP-3 alteration was promoter hypermethylation, identified in 8 of 18 (44%) PETs. It was tumor-specific and corresponded to loss or strong reduction of TIMP-3 protein expression. Notably, 11 of 14 (79%) PETs with metastases had TIMP-3 alterations, compared with only 1 of 7 (14%) PETs without metastases (P < 0.02). These data suggest a possibly important role of TIMP-3 in the tumorigenesis of human PETs, especially in the development of metastases, which has to be further evaluated in large-scale studies. 相似文献
Phenotype-driven approaches to gene discovery using inbred mice have been instrumental in identifying genetic determinants of inherited blood dyscrasias. The recessive mutant scat (severe combined anemia and thrombocytopenia) alternates between crisis and remission episodes, indicating an aberrant regulatory feedback mechanism common to erythrocyte and platelet formation. Here, we identify a missense mutation (G125V) in the scat Rasa3 gene, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis episodes. The mutation causes mislocalization of RASA3 to the cytosol in scat red cells where it is inactive, leading to increased GTP-bound Ras. Erythropoiesis is severely blocked in scat crisis mice, and ~94% succumb during the second crisis (~30 d of age) from catastrophic hematopoietic failure in the spleen and bone marrow. Megakaryopoiesis is also defective during crisis. Notably, the scat phenotype is recapitulated in zebrafish when rasa3 is silenced. These results highlight a critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis. 相似文献