Divalproex in the treatment of bipolar depression: a placebo-controlled study

BACKGROUND: The treatment of bipolar disorder in the depressed phase is complicated by a tendency for conventional antidepressant drugs to worsen the course of the illness by precipitating a manic episode or increasing cycle frequency. Thus, the potential antidepressant efficacy of mood stabilizers, such as divalproex, which is an effective treatment for the manic phase of bipolar disorder, is of considerable interest. METHODS: The clinical efficacy of divalproex (valproate, Depakote) was tested in an 8-week, double-blind, placebo-controlled, randomized clinical trial in 25 outpatients with bipolar I depression. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression, and secondary measures included the Hamilton Rating Scale for Anxiety, the Clinician Administered Rating Scale for Mania, and the Clinical Global Impression scale. RESULTS: Using repeated measures ANOVA with last observation carried forward, divalproex was more effective than placebo in improving symptoms of depression (p = 0.0002) and symptoms of anxiety (p = 0.0001) than placebo. LIMITATIONS: The sample size was small, and most patients were male. CONCLUSIONS: These pilot results indicate that divalproex is effective in reducing the symptoms of depression and anxiety in bipolar I, depressed phase. These positive results support the need to perform a larger, multisite study of divalproex treatment for bipolar depression.     

The concept of decisional control: building the base for evidence-based nursing practice

PURPOSES: The purposes of this article are to add clarification to the meaning of decisional control and provide a review of research related to the concept. DEFINITIONS AND CHARACTERISTICS OF DECISIONAL CONTROL: A summary of the definitions of decisional control is followed by a discussion of the characteristics of the concept. The concept of decisional control includes the ability or power to decide what will be one's involvement in health care decisions. REVIEW OF RESEARCH: Studies on decisional control have tended to center on inpatient, physician office, or clinic settings with a focus on the diagnosis of cancer in which multiple medical treatment decisions arise. Most of the research thus far has been performed in the United States and Canada related to medical treatment. At this point, it is not entirely clear how patient preferences for decisional control relate to health outcomes. MEASURING DECISIONAL CONTROL: An overview of the tools available to measure decisional control follows the review of the research. FUTURE DIRECTION: Future research needs to focus on the identification of the differences in decisional control by country, in differing cultural and ethnic groups within countries, and in various geographical areas of countries. The relationship of patient characteristics (e.g., age, gender, education, and income) to decisional control preferences is not clearly identified. A large gap in the research relates to how nurses can facilitate preferred decisional control to improve patient outcomes through evidence-based nursing practice.     

Are there phases to the vaso-occlusive painful episode in sickle cell disease?

The purpose of this study was to describe the pain experience of children with sickle cell disease who were hospitalized for vaso-occlusive painful episodes. The pain experience, and signs and symptoms prior to admission and during hospitalization, are presented in the context of whether there is evidence to support the existence of phases to a vaso-occlusive painful episode. Children were interviewed about the onset of the painful episode and were asked to describe their pain from the day of admission to the day of discharge from the hospital. They were also observed for the absence or presence of signs and symptoms associated with the painful vaso-occlusive episode. Findings from this study provide some evidence to support previous observations related to changes during the evolution of painful episodes that may be occurring in phases (e.g., evolving, inflammatory, resolving), as previously described in adults and children. These phases had different names, although the concepts were similar.     

Does a pre-hospital emergency pathway improve early diagnosis and referral in suspected stroke patients? – Study protocol of a cluster randomised trial [ISRCTN41456865]

Background  

Early interventions proved to be able to improve prognosis in acute stroke patients. Prompt identification of symptoms, organised timely and efficient transportation towards appropriate facilities, become essential part of effective treatment. The implementation of an evidence based pre-hospital stroke care pathway may be a method for achieving the organizational standards required to grant appropriate care. We performed a systematic search for studies evaluating the effect of pre-hospital and emergency interventions for suspected stroke patients and we found that there seems to be only a few studies on the emergency field and none about implementation of clinical pathways.     

Utility of cranial boost in addition to total body irradiation in the treatment of high risk acute lymphoblastic leukemia

PURPOSE: Total body irradiation (TBI) as part of a conditioning regimen before hematopoietic stem cell transplant (HSCT) is an important component in the management of acute lymphoblastic leukemia (ALL) that has relapsed or has other certain high-risk features. Controversy exists, however, as to whether a cranial boost in addition to TBI is necessary to prevent central nervous system (CNS) recurrences in these high-risk cases. Previous national trials have included a cranial boost in the absence of data to justify its use. Therefore, the aim of this study was to assess risk of CNS recurrence in ALL patients treated with TBI, to identify subsets of these high-risk patients at an increased or decreased risk of CNS recurrence after TBI, and to investigate whether regimens with higher doses of cranial irradiation further reduce the risk of CNS recurrence. METHODS AND MATERIALS: Charts of 67 consecutively treated patients with ALL who received TBI before HSCT were reviewed. Data including patient demographics, clinical features at presentation, conditioning regimen, donor source, use of a cranial boost, remission stage at transplant, histologic subtype, cytogenetics, and extramedullary site of presentation were retrospectively collected and correlated with the risk of subsequent CNS recurrence. RESULTS: At the time of analysis, 30 (45%) patients were alive with no evidence of disease, 8 (12%) were alive with recurrence of leukemia, 7 (10.5%) had recurrent ALL but with successful salvage, 7 (11%) died subsequent to recurrence, 14 (21%) died from complications related to HCST, and 1 patient was lost to follow-up (1.5%). Of the patients who recurred after HSCT, the relapses were hematologic in 13 (57%), CNS with or without simultaneous marrow involvement in 3 (13%), and other sites in 7 (30%). Forty-one (61%) patients did not receive an extracranial boost of irradiation with TBI. Two of these patients (4.9%) suffered CNS failures compared with 1 of 26 (3.8%) who received a cranial boost (p = 0.84). None of the 40 patients who presented only with hematologic disease developed a CNS recurrence despite the fact that only 13 of 40 of these patients received a cranial boost after TBI. Cranial boost was therefore not associated with a reduction in CNS recurrence, especially in patients with only hematologic disease at presentation for which there were no failures regardless of the use of additional cranial radiotherapy. CONCLUSIONS: Patients who present with hematologic disease only at the time of HSCT have a low risk of CNS recurrence after TBI regardless of the use of a cranial boost, suggesting that a cranial boost may not be necessary in these patients.     

An observational study of health-related quality of life and pain outcomes in chronic low back pain patients treated with fentanyl transdermal system

BACKGROUND: The analgesic effect of long-acting opioids, such as transdermal fentanyl, has been demonstrated in patients with cancer, neuropathic pain and chronic low back pain (CLBP). However, the broader effect of long-acting opioids on the patient's health-related quality of life (HRQoL) is less well known. OBJECTIVE: To evaluate HRQoL outcomes in CLBP patients treated with transdermal fentanyl. RESEARCH DESIGN AND METHODS: An observational study was conducted at 17 clinical centers in the US. Eligible patients had CLBP diagnosis for at least 3 months and were taking short-acting opioids chronically, and then initiated transdermal fentanyl treatment. Patients completed the Treatment Outcomes in Pain Survey (TOPS), which includes the SF-36 Health Survey, at baseline and > or = 9 weeks of treatment. The HRQoL burden of CLBP was determined by comparing CLBP patients' SF-36 scores to the general US population and low back pain patient norms. HRQoL outcomes were determined by comparing baseline and follow-up TOPS and SF-36 scores. Additionally, HRQoL outcomes were evaluated across patient groups stratified by changes in pain intensity ratings as measured by an 11-point numerical rating scale. RESULTS: At baseline CLBP patients (N = 131) scored one-to-two standard deviations (SD) below age and gender adjusted SF-36 general population norms (MANOVA F = 127.1, p < 0.0001) and significantly lower than low back pain norms (MANOVA F = 125.3, p < 0.0001). At follow-up, significant improvement (p < 0.05) was observed on six of the SF-36 scales and both SF-36 summary measures and five of the six TOPS pain-related scales. The magnitude of change in scores in effect size units among these scales ranged from 0.17 to 0.80, which are considered small to large effect size changes. HRQoL score improvement was greatest among patients experiencing the greatest pain relief. CONCLUSION: CLBP patients who chronically used short-acting opioids showed tremendous HRQoL burden. Favorable HRQoL outcomes were observed among patients who reported pain relief.     

Structure-based design and discovery of protein tyrosine phosphatase inhibitors incorporating novel isothiazolidinone heterocyclic phosphotyrosine mimetics

Structure-based design led to the discovery of novel (S)-isothiazolidinone ((S)-IZD) heterocyclic phosphotyrosine (pTyr) mimetics that when incorporated into dipeptides are exceptionally potent, competitive, and reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B). The crystal structure of PTP1B in complex with our most potent inhibitor 12 revealed that the (S)-IZD heterocycle interacts extensively with the phosphate binding loop precisely as designed in silico. Our data provide strong evidence that the (S)-IZD is the most potent pTyr mimetic reported to date.