A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

The effectiveness of diversion programmes for offenders using Class A drugs: a systematic review and meta-analysis

Aims: To review existing evidence on effectiveness of community-based diversion programmes for Class A drug-using offenders.

Methods: 31 databases were searched for studies published 1985–2012 (update search 2012–2016) involving community-based Criminal Justice System diversion of Class A drug users via voluntary or court-mandated treatment.

Findings: 16 studies were initially included (US, 10; UK, 4; Canada, 1; Australia, 1). There was evidence for a small impact of diversion to treatment on drug use reduction (primary Class A drug use: OR 1.68, CI 1.12–2.53; other drug use: OR 2.60, 1.70–3.98). Class A drug users were less likely to complete treatment (OR 0.90, 0.87–0.94) than users of other drugs. There was uncertainty surrounding results for offending, which were not pooled due to lack of outcome measure comparability and heterogeneity. Individual studies pointed to a minor effect of diversion on offending. Findings remained unchanged following an update review (evidence up to March 2016: US, 3; Australia, 1).

Conclusions: Treatment accessed via community-based diversion is effective at reducing drug use in Class A drug-using offenders. Evidence of a reduction in offending amongst this group as a result of diversion is uncertain. Poor methodological quality and data largely limited to US methamphetamine users limits available evidence.     

Increased circulating CSF-1 (M-CSF) in myeloproliferative disease: association with myeloid metaplasia and peripheral bone marrow extension

Myeloproliferative disease (MPD) is heterogeneous in phenotypic expression and may display features consistent with expansion and activation of the monocyte/macrophage population during its course. The role of colony-stimulating factor-1 (CSF-1) in the pathophysiology of MPD was investigated by measuring circulating CSF-1 levels and examining their relationship to disease phenotype. Serum CSF-1 concentrations, measured by radioimmunoassay, were elevated in all MPD phenotypes. CSF-1 levels differed significantly between groups of patients with essential thrombocythemia, polycythemia vera, and postpolycythemic or agnogenic myeloid metaplasia (in ascending order). CSF-1 serum levels were positively correlated with spleen size and the degree of peripheral bone marrow extension, determined by scintigraphy using a macrophage-seeking isotope. There was no correlation between CSF-1 concentration and circulating levels of erythrocytes, neutrophils or platelets, or the presence of bone marrow fibrosis. Elevated serum CSF-1 levels appear to be associated with an expanded monocyte/macrophage population in MPD. In view of the known cooperativity between CSF-1 and other growth factors in regulating hematopoiesis, the finding of increased serum CSF-1 concentrations and its association with myeloid metaplasia and bone marrow extension may indicate a pathophysiologic role for CSF-1 in determining the phenotypic expression of MPD.     

动态监测血清相关指标对重型颅脑损伤术后肺部感染的预测价值

目的分析动态监测重型颅脑损伤术后患者血清降钙素原(PCT)、可溶性髓样细胞表达的激发受体-1(sTREM-1)及C反应蛋白与白蛋白比值(CRP/ALB)的变化对肺部感染的早期预测价值。方法选取手术治疗的196例重型颅脑损伤患者,监测并记录术后1、3、5 d的血清PCT、CRP、ALB、sTREM-1及CRP/ALB水平,记录患者术后肺部感染情况。分析重型颅脑损伤术后肺部感染的危险因素,通过绘制受试者工作特征(ROC)曲线分析相关指标对肺部感染的早期预测价值。结果重型颅脑损伤术后发生肺部感染者76例(38.78%),感染发生时间为术后6~13 d,中位数为7 d。无肺部感染组术后3、5 d血清PCT、sTREM-1及CRP/ALB低于肺部感染组,差异有统计学意义(P0.05);肺部感染组术后5 d血清ALB低于无肺部感染组,差异有统计学意义(P0.05)。机械通气时间、术后格拉斯哥昏迷量表(GCS)评分、术后急性生理与慢性健康评分Ⅱ(APACHEⅡ)以及术后5 d血清PCT、sTREM-1及CRP/ALB是术后肺部感染的独立危险因素(P0.05)。ROC曲线显示,单独检测时,术后5 d血清CRP/ALB预测肺部感染的曲线下面积(AUC)值、约登指数、特异度最高,sTREM-1预测的敏感度最高;联合检测的AUC、约登指数、灵敏度、特异度均高于单独检测。肺部感染诊断时临床肺部感染评分(CPIS)、全身炎症反应综合征修正(ASS)评分均与术后5 d PCT、sTREM-1、CRP/ALB水平呈显著正相关(P0.05)。结论术后5 d血清PCT、sTREM-1及CRP/ALB水平均可作为重型颅脑损伤术后肺部感染早期预测的有效依据,而联合检测的预测价值更高,更有利于早期对肺部感染程度及病情进展的评估。     

22例皮质醇增多症的临床研究

目的：探讨皮质醇增多症的临床表现和内分泌检查等辅助检查的意义.方法：从年龄、性别、病程及实验室检查等方面,观察22例不同原因所致皮质醇增多症患者不同的临床表现和测定实验室检查指标.结果：22例中诊断库欣病（增生型）14例[63.6％,其中13例（92.9％）得到MRI检查证实],肾上腺腺瘤6例[27.3％,均得到MRI检查证实（100％）],另有肾上腺结节样增生1例（4.5％）,异位ACTH综合征1例（4.5％）.临床表现：按出现的频率前4位依次为,库欣病：高血压（100％）、满月脸（92.9％）、向心性肥胖（85.7％）、多血质（85.7％）,肾上腺腺瘤：高血压（100％）、满月脸（100％）、向心性肥胖（100％）、多血质（83.3％）.实验室检查：小剂量地塞米松不能抑制：库欣病与肾上腺腺瘤均为100％.结论：根据高血压、满月脸、向心性肥胖,小剂量地塞米松抑制试验和MRI检查可诊断绝大多数皮质醇增多症.     

Patient‐reported convenience of once‐daily versus three‐times‐daily dosing during long‐term studies of pramipexole in early and advanced Parkinson’s disease

Background and purpose: In chronic diseases including Parkinson’s disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less‐effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical‐trial designs preclude direct comparisons of adherence to various schedules. Methods: In two double‐blind (DB) studies of early PD and one of advanced PD, subjects received three‐times‐daily (t.i.d.) pramipexole or placebo. In open‐label (OL) extensions, subjects took extended‐release, once‐daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. Results: Of 590 DB‐trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it ‘very much more convenient’ and 27.8%‘more convenient’), 2.7% preferred t.i.d., and 2.9% chose ‘no difference’. Of 465 DB‐trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it ‘very much more convenient’ and 40.1%‘more convenient’), 5.7% preferred t.i.d., and 5.4% chose ‘no difference’. Results excluding DB‐placebo recipients were highly similar. Conclusions: In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine‐agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced‐PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.     

Cerebellar pilocytic astrocytoma in adults: a management paradigm for a rare tumour

Background

Pilocytic astrocytoma is one of the commonest subtypes of glioma to affect children. However, they are rarely diagnosed in patients over the age of 18 years. In adults, these tumours appear more frequently supra-tentorially than in the cerebellum and some reports suggest a different clinical course in adults. We reviewed ten patients aged 18 or over who had been operated on for cerebellar pilocytic astrocytoma to assess the impact of tumour biology and extent of resection on outcome in adults.

Method

Patients were identified from a neuropathology database and a retrospective chart review of ten patients was performed. Recorded data included patient demographics, tumour location, presenting features, radiological appearance, extent of surgical resection, tumour recurrence and Ki-67 proliferation index.

Results

Nine patients were men and one patient was a woman. Median follow up is 41.5 months (range 15–334 months). Complete surgical resection was achieved in nine of the patients operated in our institution. One patient had prior subtotal resection elsewhere. Tumour recurrence was seen only in the two patients with subtotal resection, at 7 and 25 years. Ki-67 ranged from <1 to 10 % and appears to have no correlation to recurrence. No patients in this series had adjuvant treatment.

Conclusions

Cerebellar pilocytic astrocytomas in adults should be treated with macroscopic complete surgical resection whenever possible. If this is achieved, long-term survival rates are excellent, whereas subtotal resection carries a high risk of tumour recurrence. Ki-67 is less important prognostically than the extent of initial resection.