Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

人谷胱甘肽S－转移酶基因π（cDNA）的筛选和鉴定

采用免疫筛选法和寡核苷酸探针筛选法从人肺ｃＤＮＡ文库中筛选得到人ＧＳＴ一ｐｉ（ＧＳＴ－ｘ）ｃＤＮＡ，对其序列进行了测定和分析。     

Trusting and misleading. Parents’ and children’s communication and negotiation about alcohol as described by teenagers

Background: Typically, research on parents’ and children’s interactions around alcohol issues focuses on how parenting styles and parents’ examples affect teenager’s drinking habits. In this paper, we approach the theme from the youngsters’ perspective. We ask how teenagers describe the interaction on alcohol-related issues with their parents and how they would like their parents to act during these interactions.

Data and methods: The article applies the concept of trust, which is seen as a feature connecting all kinds of communities, and especially families. We pay attention to whether alcohol issues challenge trustful relations and give rise to contradictions and complications in the interactions between parents and children.

Results: The analysis shows the ways how trust is maintained and challenged in teenagers? accounts of communication regarding alcohol with their parents. It also shows that although trust is tested in several ways, it is essential for teenagers. Even though teenagers tell how they can mislead their parents by using strategies that challenge trust, they nevertheless highlight the importance of trusting ties with parents. Teenagers do not exclude their parents from alcohol-related discussion but expect rules, communication and authority from them. Our data suggest that teenagers also want to protect their parents from disappointments caused by their own actions.

Conclusions: A trusting parent–child relationship, based on dialog rather than opposition, seems to play a significant role in guiding teenagers’ alcohol-related attitudes and practices.     

Low cdc27 and high securin expression predict short survival for breast cancer patients

Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase–anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow‐up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti‐mitotic drug development.     

De Novo Mutations in the Motor Domain of KIF1A Cause Cognitive Impairment,Spastic Paraparesis,Axonal Neuropathy,and Cerebellar Atrophy

KIF1A is a neuron‐specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type‐2. Here, we report 11 heterozygous de novo missense mutations (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, and p.R316W) in KIF1A in 14 individuals, including two monozygotic twins. Two mutations (p.T99M and p.E253K) were recurrent, each being found in unrelated cases. All these de novo mutations are located in the motor domain (MD) of KIF1A. Structural modeling revealed that they alter conserved residues that are critical for the structure and function of the MD. Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons. Individuals with de novo mutations in KIF1A display a phenotype characterized by cognitive impairment and variable presence of cerebellar atrophy, spastic paraparesis, optic nerve atrophy, peripheral neuropathy, and epilepsy. Our findings thus indicate that de novo missense mutations in the MD of KIF1A cause a phenotype that overlaps with, while being more severe, than that associated with recessive mutations in the same gene.     

Patient Health Literacy and Communication with Providers Among Women Living with HIV: A Mixed Methods Study

AIDS and Behavior - In this mixed-methods study, we examine the relationship between provider communication and patient health literacy on HIV continuum of care outcomes among women living with HIV...     

Comparison of once-daily intravenous and oral omeprazole on pentagastrin-stimulated acid secretion in duodenal ulcer patients.

The effect of 5 days of once-daily dosing with 20 mg p.o. and 40 mg i.v. omeprazole on pentagastrin-stimulated acid secretion was studied in 8 patients with duodenal ulcer. In addition they also received a 10-mg i.v. dose on day 6 during the oral treatment period. The antisecretory effect was measured 6-7 h after dose at a time point when maximal inhibition during the dosing interval is anticipated. The median percent inhibition of peak acid output (PAO) markedly increased from 43% on day 1 to 100% on day 5 during treatment with 20 mg p.o. The first 40-mg i.v. dose produced a median inhibition of 98% of PAO already on day 1. After 5 days of dosing, the inhibition had increased to 100%. On the other hand, a 10-mg i.v. dose could essentially maintain the degree of PAO reduction reached after 5 days of oral treatment. Plasma omeprazole concentrations increased during repeated dosing both with 20 mg p.o. and 40 mg i.v.