The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low‐dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti‐inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non‐fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at‐risk groups include an HIV test, a QuantiFERON‐TB Gold test and a chest X‐ray. In patients without complications, repeat the FBC at 2–4 weeks, then every 3–6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low‐dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment‐emergent liver toxicity is related to underlying metabolic syndrome and non‐alcoholic fatty liver disease or non‐alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: ‘20 mg/day’ has been corrected to ‘20 gm/day’.] Although MTX is a potential teratogen post‐conception, there is little evidence for this pre‐conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri‐surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti‐tumour necrosis factor biologics.     

The role of hydroxychloroquine in the treatment of lichen planopilaris: A retrospective case series and review

A variety of systemic agents are used to treat lichen planopilaris (LPP) with a limited evidence base. The aim of our study was to retrospectively review the response rate to and tolerability of hydroxychloroquine in a cohort of patients with LPP in an effort to add to the evidence base for its use. Twenty‐three patients with a clinical and histopathological diagnosis of LPP who had been treated with hydroxychloroquine for their disease in a single center were identified. A retrospective review of these patients' medical records was performed and physician rated response was documented. Complete response was observed in 61% of our patients, and a further 9% of patients demonstrated partial response. Thirteen percent of patients withdrew from treatment because of suspected adverse effects. Our sample size was small, and data was collected retrospectively. We found hydroxychloroquine to be a reasonable therapeutic choice in LPP.     

Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance

OBJECTIVE: To assess the relationship between impaired glucose tolerance and both vascular dementia and AD. BACKGROUND: Diabetes and abnormalities of glucose metabolism have been associated with stroke and poor cognitive function. In addition, glycoproteins and glycosylation have been postulated to be associated with the development of neuritic plaques characteristic of AD. METHODS: A historical prospective cohort study of Japanese-American men (n = 3,774), who were examined at ages 45 to 68 (1965 through 1968) and again at ages 71 to 93 (1991 through 1993). Measurements were obtained by clinical and home examinations: assessment of glucose intolerance (nonfasting 1 hour after glucose load) from 1965 through 1968 and history of diabetes diagnosed by a physician at examinations given from 1965 through 1968 and from 1976 through 1978. At the 1991 through 1993 examinations, the Cognitive Assessment Screening Instrument (CASI)-an instrument designed for use in cross-cultural settings combining features of the Folstein Mini-Mental State Examination, the Modified Mini-Mental State Examination, and the Hasegawa Dementia Screening Scale-was used. Diagnosis and classification of AD and vascular dementia were made by a consensus panel using neuropsychologic assessment data, a neurologist's evaluation, and information from a family informant. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria were used to establish dementia, and subclassification by cause was based on other published criteria. RESULTS: No association between AD and diabetes, present either 25 or 15 years previously, was found after adjustment for age and education in a multiple regression model. A significant association was found between impaired glucose tolerance at baseline and vascular dementia (p < 0.01). CONCLUSIONS: These findings confirm expected relationships between impaired glucose tolerance and stroke-related dementia but do not support an association of disordered glucose metabolism with AD.     

Predictors of functional status at service entry and discharge among young people with first episode psychosis

Objective

Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment.

Method

A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status).

Results

52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline.

Conclusions

Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.

     

Die Bestimmung des i.m. Morphin-Äquivalents zur Therapie des Krebsschmerzes mit verschiedenen Opioiden oder beim Wechsel des Verabreichungsweges

During the long-term treatment with opioids it is sometimes important to switch the opioid or change the route of administration. The estimation of morphine-equivalents can be helpful in this range because it clarifies the dose in milligramm required for different clinical situations. The basis of this estimation is the equianalgesic potency of opioids. One i.m. morphine-equivalent is the analgesic dose of an opioid (i.m. injected) equal to the analgesic effect of 1 mg morphine (i.m.). The relationships between equianalgesic doses and intramuscular and oral routes of applications are listed in tables. The cross-tolerance between different opioids during long-term treatment is not complete. To avoid an overdose, we suggest a reduction in the calculated opioid dose of 50%. Additional "rescue doses" can be used during the period immediately the change to provied satisfactory pain control. A new opioid dosage should be calculated every 24 hours based on the basaline dose plus the total quantity of "rescue" medication required by the patient. Useful starting point for calculation an effective dose when changing from one opioid or route of administration to another can result in improved pain control that is more responsive to patient need. The limitations are 1. individual differences in the response to opioids, especially during long-term treatment and in the development of analgesic tolerance, 2. individual differences in the response to alternatives routes of administration, and 3. the unknown degree of cross tolerance among opioid drugs. The scientific meaning of the estimation of i.m. morphine-equivalent is discussed.     

转化生长因子β1在大鼠纤维化腹膜组织中的表达及作用

目的:检测转化生长因子β1在腹膜透析大鼠腹膜内表达,并探讨其在腹膜纤维化中的意义。方法:实验于2005-06/2006-03在中南大学湘雅二医院肾内科实验室完成。①实验材料:雄性SD大鼠,体质量180～240g,由中南大学湘雅二医院动物实验中心提供。②实验方法:将28只大鼠按随机数字表随机分为4组,每组7只。正常对照组不予任何干预;生理盐水组腹腔注射20mL生理盐水;低糖透析液组腹腔注射20mL1.5%葡萄糖透析液;高糖透析液组腹腔注射20mL4.25%葡萄糖透析液,均为1次/d。4周后,向大鼠腹腔注射4.25%葡萄糖腹膜透析液20mL,4h后于大鼠右下腹缓慢插入带有多个侧孔的10号静脉留置针,缓慢低位引流腹透液,量取引流液。③实验评估:取大鼠壁层腹膜组织,以苏木素-伊红染色,镜下测量腹膜厚度,采用免疫组织化学方法检测大鼠腹膜中转化生长因子β1及纤连蛋白。结果:28只大鼠均进入结果分析。①高糖透析液组、低糖透析液组超滤量均明显低于正常对照组与生理盐水组,并且高糖透析液组超滤量明显少于低糖透析液组(P均<0.05)。②高糖透析液组腹膜明显增厚,表面粗糙,间皮细胞肿胀,脱落,间皮下有大量血管生成以及胶原纤维沉积,还可见单核细胞等炎症细胞浸润,与其他组比较,腹膜厚度明显增加(P<0.05)。③高糖透析液组转化生长因子β1、纤连蛋白表达量均明显高于其他组;低糖透析液组转化生长因子β1、纤连蛋白表达量均明显高于正常对照组与生理盐水组(P<0.05)。④大鼠腹膜组织转化生长因子β1蛋白与纤连蛋白表达量、腹膜厚度之间呈明显的正相关(r=0.86,0.83,P<0.05)。结论:葡萄糖透析液可诱导腹膜组织转化生长因子β1明显上调,腹膜转化生长因子β1高表达与腹膜透析腹膜纤维化密切相关。