Developing a healthy living intervention for people with early psychosis using the Medical Research Council's guidelines on complex interventions: phase 1 of the HELPER - InterACT programme

BackgroundYoung people with early psychosis often gain a significant amount of weight after the initiation of anti-psychotic treatment. Despite the current policy guidance to develop and evaluate ‘healthy living’ interventions for people with psychosis there remains a paucity of research. Our aim was to develop an acceptable, feasible, culturally sensitive and potentially effective ‘healthy living’ intervention, specifically for young people with early psychosis.MethodsUsing the Medical Research Council guidelines for developing and evaluating complex interventions we conducted a number of studies to devise a ‘healthy living’ intervention. We used a ‘top down’ (published evidence), bottom up (stakeholder perspectives) approach, which included updating a systematic review, identifying a theoretical basis for the intervention, exploring the perspectives of service users and health professionals, and identifying key cultural issues. The results of these studies were synthesised to determine the content and delivery of the intervention.ResultsThe intervention developed comprised eight individual sessions to be delivered by a support time recovery worker over a 12 month period with emphasis on individualised action plans to facilitate participatory exercise and changes in diet. To optimise engagement, choice and self management a booklet and website were developed to provide participants with educational advice, healthy eating recipes and other materials.ConclusionUsing the Medical Research Council guidelines we have developed a potentially effective, feasible and acceptable ‘healthy living’ intervention for people with psychosis using early intervention services in the UK.     

Rapid protection of gnotobiotic pigs against experimental salmonellosis following induction of polymorphonuclear leukocytes by avirulent Salmonella enterica

Oral inoculation of 5-day-old gnotobiotic pigs with Salmonella enterica serovar Typhimurium strain F98 resulted in severe enteritis and invasive disease. Preinoculation 24 h earlier with an avirulent mutant of Salmonella enterica serovar Infantis (1326/28) completely prevented disease for up to 14 days (when the experiment was terminated). S. enterica serovar Infantis colonized the alimentary tract well, with high bacterial counts in the intestinal lumen but with almost no invasion into the tissues. Unprotected pigs had high S. enterica serovar Typhimurium counts in the intestines, blood, and major nonintestinal organs. Recovery of this strain from the blood and major organs in S. enterica serovar Infantis-protected pigs was substantially reduced despite the fact that intestinal counts were also very high. Protection against disease thus did not involve a colonization exclusion phenomenon. Significant (P < 0.05) infiltration of monocytes/macrophages was observed in the submucosal regions of the intestines of both S. enterica serovar Infantis-protected S. enterica serovar Typhimurium-challenged pigs and unprotected S. enterica serovar Typhimurium-challenged pigs. However, only polymorphonuclear neutrophils (PMNs) were observed throughout the villus, where significant (P < 0.05) numbers infiltrated the lamina propria and the subnuclear and supranuclear regions of the epithelia, indicating that PMN induction and positioning following S. enterica serovar Infantis inoculation was consistent with rapid protection against the challenge strain. Similarly, in vitro experiments using a human fetal intestinal epithelial cell line (INT 407) demonstrated that, although significantly (P < 0.05) fewer S. enterica serovar Infantis than S. enterica serovar Typhimurium organisms invaded the monolayers, S. enterica serovar Infantis induced an NF-kappaB response and significantly (P < 0.05) raised interleukin 8 levels and transmigration of porcine PMN. The results of this study suggest that attenuated Salmonella strains can protect the immature intestine against clinical salmonellosis by PMN induction. They also demonstrate that PMN induction is not necessarily associated with clinical symptoms and/or intestinal pathology.     

The effect of strength training and short-term detraining on maximum force and the rate of force development of older men

This study examined the effect of strength training (ST) and short-term detraining on maximum force and rate of force development (RFD) in previously sedentary, healthy older men. Twenty-four older men (70–80 years) were randomly assigned to a ST group (n = 12) and C group (control, n = 12). Training consisted of three sets of six to ten repetitions on an incline squat at 70–90% of one repetition maximum three times per week for 16 weeks followed by 4 weeks of detraining. Regional muscle mass was assessed before and after training by dual-energy X-ray absorptiometry. Training increased RFD, maximum bilateral isometric force, and force in 500 ms, upper leg muscle mass and strength above pre-training values (14, 25, 22, 7, 90%, respectively; P < 0.05). After 4 weeks detraining all neuromuscular variables were significantly (P < 0.05) lower than after 16 weeks training but remained significantly (P < 0.05) higher than pre-training levels except for RFD which had returned to pre-training levels. These findings demonstrate that high-intensity ST can improve maximum force and RFD of older men. However, older individuals may lose some neuromuscular performance after a period of short-term detraining and that resistance exercise should be performed on a regular basis to maintain training adaptations.     

Collaborative care for depression in UK primary care: a randomized controlled trial

BACKGROUND: Collaborative care is an effective intervention for depression which includes both organizational and patient-level intervention components. The effect in the UK is unknown, as is whether cluster- or patient-randomization would be the most appropriate design for a Phase III clinical trial. METHOD: We undertook a Phase II patient-level randomized controlled trial in primary care, nested within a cluster-randomized trial. Depressed participants were randomized to 'collaborative care' - case manager-coordinated medication support and brief psychological treatment, enhanced specialist and GP communication - or a usual care control. The primary outcome was symptoms of depression (PHQ-9). RESULTS: We recruited 114 participants, 41 to the intervention group, 38 to the patient randomized control group and 35 to the cluster-randomized control group. For the intervention compared to the cluster control the PHQ-9 effect size was 0.63 (95% CI 0.18-1.07). There was evidence of substantial contamination between intervention and patient-randomized control participants with less difference between the intervention group and patient-randomized control group (-2.99, 95% CI -7.56 to 1.58, p=0.186) than between the intervention and cluster-randomized control group (-4.64, 95% CI -7.93 to -1.35, p=0.008). The intra-class correlation coefficient for our primary outcome was 0.06 (95% CI 0.00-0.32). CONCLUSIONS: Collaborative care is a potentially powerful organizational intervention for improving depression treatment in UK primary care, the effect of which is probably partly mediated through the organizational aspects of the intervention. A large Phase III cluster-randomized trial is required to provide the most methodologically accurate test of these initial encouraging findings.     

Evaluation of the anticonvulsant and muscle relaxant effects of the methanol root bark extracts of Annona senegalensis

ObjectiveTo investigate the potentials of the root bark of Annona (A.) senegalensis in the control of seizure and related hypnotic and motor incoordination effects in mice using experimental models.MethodsThe methanol extract (ME) of the root bark of A. senegalensis was studied in mice using pentylenetetrazole (PTZ) induced convulsions, phenobarbitone induced sleeping time and motor coordination test on rota-rod performance. Acute toxicity and lethality (LD₅₀) test as well as phytochemical analysis were also carried out.ResultsThe extract (200, 400, 800 mg/kg) exhibited a non-dose dependent significant (P <0.05) delay in the onset of both tonic and clonic phases of seizure induced by PTZ (60 mg/kg, s.c.) as well as offered a 100% protection (200 mg/kg) in mice from PTZ induced seizures. The extract significantly (P <0.05) decreased the latency and increased the duration of phenobarbitone induced sleeping time. At 200 mg/kg, the extract exhibited a significant (P <0.05) motor incoordination. The acute toxicity test revealed an oral LD₅₀ of 1 296 mg/kg, while the phytochemical studies showed the presence of alkaloids, resins, glycosides, carbohydrate, reducing sugar, flavonoids, terpenoids, saponins and tannins.ConclusionThe extract of A. senegalensis possessed anticonvulsant activity with pronounced hypnotic and muscle relaxant effects.     

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目的探讨瘦素质量浓度与早期静脉营养及生长发育的关系。方法新疆医科大学第一附属医院新生儿科于2005-01—2006-02,将收治的86例早产适于胎龄儿用随机数字表法分为观察组(早期微量喂养同时辅助胃肠外营养组)45例和对照组(单纯早期微量喂养组)47例,分别测定脐血及第7天血清瘦素质量浓度,同时监测营养状况和生长发育指标,并作对比分析。结果(1)观察组与对照组脐血瘦素质量浓度分别为(4.6±3.7)ng/mL、(4.8±2.2)ng/mL,生后第7天两组瘦素质量浓度分别为(4.3±2.2)ng/mL、(3.1±1.7)ng/mL。对照组第7天血清瘦素质量浓度明显低于脐血(P<0.05),而观察组其差异无统计学意义(P>0.05)。(2)脐血瘦素质量浓度与出生体重、胎龄成正相关(r=0.56、r=0.67)。(3)观察组第7天热卡及蛋白质摄入量、血清瘦素质量浓度、皮褶厚度变化值与对照组相比,差异有统计学意义(P<0.05)。结论对早产儿应尽早喂养,同时需要胃肠外营养作为肠内营养的补充。瘦素可作为新生儿营养效果判定的实验室指标之一。     

Human blood PIG-A mutation and micronucleated reticulocyte flow cytometric assays: Method optimization and evaluation of intra- and inter-subject variation

We previously described flow cytometry-based methods for scoring the incidence of micronucleated reticulocytes (MN-RET) and PIG-A mutant phenotype reticulocytes (MUT RET) in rodent and human blood samples. The current report describes important methodological improvements for human blood analyses, including immunomagnetic enrichment of CD71-positive reticulocytes prior to MN-RET scoring, and procedures for storing frozen blood for later PIG-A analysis. Technical replicate variability in MN-RET and MUT RET frequencies based on blood specimens from 14 subjects, intra-subject variability based on serial blood draws from 6 subjects, and inter-subject variation based on up to 344 subjects age 0 to 73 years were quantified. Inter-subject variation explained most of the variability observed for both endpoints (≥77%), with much lower intra-subject and technical replicate variability. The relatively large degree of inter-subject variation is apparent from mean and standard deviation values for MN-RET (0.15 ± 0.10%) and MUT RET (4.7 ± 5.0 per million, after omission of two extreme outliers). The influences of age and sex on inter-subject variation were investigated, and neither factor affected MN-RET whereas both influenced MUT RET frequency. The lowest MUT RET values were observed for subjects <11 years old, and males had moderately higher frequencies than females. These results indicate that MN-RET and MUT RET are automation-compatible biomarkers of genotoxicity that bridge species of toxicological interest to include human populations. These data will be useful for appropriately designing future human studies that include these biomarkers of genotoxicity, and highlight the need for additional work aimed at identifying the sources of inter-individual variability reported herein.