Development of the multi-attribute Pediatric Asthma Health Outcome Measure (PAHOM).

OBJECTIVE: To develop a multi-attribute outcome measure for children with asthma that allows for the calculation of quality-adjusted life years in cost-effectiveness studies and can also be used to assign preference weights to asthma-symptom-free days. STUDY DESIGN: A literature review and two interviewer-administered surveys. SETTING: Homes or community centers of participants in Seattle, United States. MAIN MEASURE: Visual analog scale (VAS), standard gamble (SG), and relative risk attitude equation techniques were used to estimate two sets of preference weights for 10 health states. The PAHOM was used to record health states of pediatric asthma patients. RESULTS: A total of 94 subjects provided complete responses without any illogical ratings to VAS questions and 101 provided the same to SG questions. The VAS preference weights of the health states range from a maximum of 1 for perfect health to a minimum of 0.03 for severe asthma symptoms, emotional problems, and activity limitations. Those based on the relative risk attitude equation constructed with both VAS and SG preference weights range from 1 to 0.06. The mean PAHOM scores of pediatric asthma patients based on VAS and converted SG preference weights were 0.70 and 0.83, respectively. CONCLUSIONS: The PAHOM calendar can be used to identify asthma patients' health outcomes, to calculate the preference weights of asthma patients' health states, and to estimate the number of symptom-free days. These factors make the PAHOM a promising instrument for use in effectiveness and cost-effectiveness studies in children with asthma.     

Sensory stimulation increases cortical expression of the fragile X mental retardation protein in vivo

Fragile X syndrome is a common cause of mental retardation that results from the absence of the fragile X mental retardation protein (FMRP), an RNA binding protein whose function remains unclear. Recent in vitro work has demonstrated that the protein is translated near the synapse in an activity dependent manner [33]. We therefore asked whether expression of FMRP might be altered by neuronal activity in vivo. Using immunoblots of different sub-cellular fractions of the rat somatosensory cortex, we show that the levels of FMRP increase significantly following unilateral whisker stimulation, a model of experience dependent plasticity. This increase is greatest between 2 and 8 h after the stimulus and is seen in both a synaptosomal fraction as well as a sub-cellular fraction enriched for polyribosomal complexes. In contrast, detectable levels of FMRP within the somatosensory cortex show either a decrease or no change after a kainic acid induced seizure compared to water treated controls. Our findings demonstrate that FMRP expression levels are modulated in vivo in response to neuronal activity and suggest a role for FMRP in activity dependent plasticity.     

Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor.

Targeted therapies that inhibit the activity of tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) have shown activity against solid malignancies when used as single agents or in combination with chemotherapy. Although anti-EGFR therapies are active in some patients, eventually disease in nearly all patients will become refractory to therapy. Therefore, a better understanding of the mechanisms of resistance to anti-EGFR therapies is critical to further improve the efficacy of this class of agents. Mechanisms that mediate resistance to anti-EGFR therapies include the presence of redundant tyrosine kinase receptors, increased angiogenesis, and the constitutive activation of downstream mediators. Two recent landmark publications have also shown that specific mutations in the kinase domain of EGFR in some lung carcinomas are associated with markedly improved response rates to an EGFR tyrosine kinase inhibitor. Mutations in the EGFR receptor seem to play a significant role in determining the sensitivity of tumor cells to EGFR inhibitor therapy by altering the conformation and activity of the receptor. As the field of molecular therapeutics continues to evolve, a comprehensive understanding of resistance mechanisms will ultimately lead to refinements in our regimens to provide better care for patients with cancer.     

Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01.

PURPOSE: To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms. PATIENTS AND METHODS: A total of 243 patients with stage II to IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m(2) intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m(2) IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs. RESULTS: A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of >/= grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87). CONCLUSION: AM did not significantly reduce esophagitis >/= grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.     

Tear of the distal biceps branchii tendon: A new method of ultrasound evaluation

Tear of the distal biceps brachii tendon is an uncommon injury. Ultrasound evaluation of the distal tendon using an anterior approach is often difficult because of technical factors. We describe a new method of ultrasound evaluation of the distal biceps tendon insertion. This involves a posterior approach with the forearm pronated. With pronation of the forearm, the radial tuberosity faces posteriorly, bringing the distal biceps tendon insertion into view. A surgically proven case of distal biceps tendon tear is presented to illustrate our technique.     

Multimorbidity and healthcare utilization among early survivors of pediatric cancer

Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009–2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4–2.1) and of a hospitalization almost four‐fold (OR, 3.8; 95% CI], 2.5–5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.     

卒中医疗体系之急诊医疗服务的实施策略:美国心脏协会/美国卒中协会急诊医疗服务体系专家组和卒中委员会的政策声明

尽管卒中的预防、诊断、治疗和康复已取得一些进展,但卒中在美国仍然是第三大死亡原因和长期残疾的主要原因.每年约有70万人新发或复发卒中[1].在过去10年里,急性卒中诊治的一些进展,包括纤溶和其他短期疗法的引入,突出显示了急诊医疗服务(emergency medical services,EMS)机构和急诊医疗服务体系(emergency medical services systems,EMSS)在优化卒中医疗中的关键作用[2-7].     

Can the Scapular Dyskinesis Test be Associated with Throwing Related Injuries During the Course of Collegiate Baseball Seasons?

BackgroundA pattern of scapular dyskinesis on the dominant side has been demonstrated to be associated with a decrease in throwing arm conditions identified by a self-report outcome assessment in collegiate baseball pitchers during the course of a single season. However, it is unclear if symptomatic shoulders in baseball pitchers may be associated with the presence of scapular dyskinesis.PurposeTo study the relationship between the presence of scapular dyskinesis and throwing-related injury in collegiate baseball pitchers during each respective course of up to four subsequent seasons.MethodsA single Division 1 National Collegiate Athletic Association team participated in this study over a four-year-period. The scapular dyskinesis test was implemented during the preseason for baseball pitchers. Players were followed throughout each respective season to track the incidence of throwing-related upper extremity injuries.ResultsA total of 36 collegiate baseball pitchers (height: 185.3 ± 5.6 cm, weight: 88.8 ± 7.8 kg, age: 20.0 ± 1.5 years) consisting of 57 pitcher seasons were followed in this study, in which 18 pitchers remained with the team for more than one year. Twenty-seven of the 57 pitchers were classified as having scapular dyskinesis demonstrated at around 90° of shoulder flexion on the throwing side. Five injuries (13.2% of a total of 38 injuries) were diagnosed as throwing-related shoulder injuries during the course of the intercollegiate baseball seasons. Four of the five throwing-related shoulder injuries occurred in pitchers who had scapular dyskinesis on their dominant side. Consequently, the odds ratio was 5.04 for the collegiate pitchers with scapular dyskinesis on the throwing arm side associated with a throwing-related shoulder injury compared to those with no scapular dyskinesis (p = 0.16). No relationship was identified between scapular dyskinesis on the throwing arm side and throwing-related elbow injury. Eighty-one percent of the scapular dyskinesis test results were not changed on the throwing side from the previous to the following year for those 18 pitchers who were followed for more than one season, whereas 42.9% of the results remained unchanged on the non-throwing side.ConclusionThe results suggest that collegiate baseball pitchers with dominant arm scapular dyskinesis likely are at increased risk of throwing-related shoulder injury.Level of evidenceLevel 2, Prospective Cohort Study     

Protease production by microorganisms associated with reproductive tract infection

Factors influencing pathogenicity of various microbes found in the female lower genital tract remain incompletely understood. Protease production by cervico/vaginal microorganisms may alter or inactivate a variety of proteins important in host defense and structural-functional integrity including collagen-containing chorioamniotic membranes and uterine cervix. Host tissues may be made more susceptible to other organisms' virulence factors by protease-producing members of genital tract local flora. Microorganisms themselves may also be influenced by the presence of other microbial protease. Nonspecific protease, gelatinase, collagenase, and elastase production was examined for in vitro with use of aerobic (30) and anaerobic (25) strains of microorganisms typical of those isolated from the lower genital tract of women with premature rupture of membranes, chorioamnionitis, and puerperal infection. Microorganisms including Bacteroides bivius, Bacteroides melaninogenicus, Bacteroides fragilis, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Proteus species, and Propionibacterium acnes produce various proteases. Protease production by both acknowledged pathogenic and commensal bacteria may contribute to the occurrence of reproductive tract morbidity including premature rupture of membranes and preterm labor.