Minimal association of common red blood cell polymorphisms with Plasmodium falciparum infection and uncomplicated malaria in Papua New Guinean school children

Southeast Asian ovalocytosis (SAO), α(+)-thalassemia, and low expression of complement receptor 1 (CR1) have been associated with protection against severe Plasmodium falciparum malaria. In a cohort of children 5-14 years of age the effect of α(+)-thalassemia, SAO (SLC4A1Δ27), CR1 polymorphisms, and Gerbich negativity (GYPCΔex3) on risk of P. falciparum infections and uncomplicated illness were evaluated. The risk of acquiring polymerase chain reaction (PCR)-diagnosed P. falciparum infections was significantly lower for α(+)-thalassemia heterozygotes (hazard ratio [HR]: 0.56) and homozygotes (HR: 0.51) than wild-type children. No such differences were seen in light of microscopy diagnosed infections (P = 0.71) or were α(+)-thalassemia genotypes associated with a reduced risk of uncomplicated P. falciparum malaria. No significant associations between the risk of P. falciparum infection or illness were observed for any of the other red blood cell polymorphisms (P > 0.2). This suggests that these polymorphisms are not associated with significant protection against P. falciparum blood-stage infection or uncomplicated malaria in school-aged children.     

Combined bezafibrate and medroxyprogesterone acetate have efficacy without haematological toxicity in elderly and relapsed acute myeloid leukaemia (AML)

Acute myeloid leukaemia (AML) causes life‐threatening deficits of functional blood cells that require management using red cell and platelet transfusion and aggressive treatment of neutropenic infections. Current cytotoxic chemotherapy further worsens the problem of reduced haemopoiesis and two‐thirds of patients are too frail to tolerate intensive chemotherapy at all. Median survival amongst these patients remains at <3 months emphasizing the urgent need for anti‐AML therapies that do not suppress haemopoiesis. Our laboratory studies showed combined Bezafibrate and Medroxyprogesterone acetate (BaP) had activity against AML without toxicity to normal stem cells. Here we report the safety and efficacy of BaP in 20 patients (19 AML, 1 high‐risk myelodysplasia) for whom intensive chemotherapy was not an option. No patient exhibited haematological toxicity from BaP. Eleven patients took BaP alone for >4 weeks. One reverted from high risk myelodysplasia and remains transfusion independent after 201 weeks of therapy. Three AML patients gained major haematological improvements for 22–30 weeks; in one, marrow was available to document a partial AML response. Thus, this trial indicates that BaP therapy has potential for treatment of elderly and relapsed AML.     

Online vs. face-to-face discussion in a Web-based research methods course for postgraduate nursing students: a quasi-experimental study

BACKGROUND: Web-based technologies are increasingly being used to create modes of online learning for nurses but their effect has not been assessed in nurse education. OBJECTIVES: Assess whether participation in face-to-face discussion seminars or online asynchronous discussion groups had different effects on educational attainment in a web-based course. DESIGN: Non-randomised or quasi-experimental design with two groups-students choosing to have face-to-face discussion seminars and students choosing to have online discussions. SETTING: The Core Methods module of a postgraduate research methods course. PARTICIPANTS: All 114 students participating in the first 2 yr during which the course teaching material was delivered online. OUTCOME: Assignment mark for Core Methods course module. METHODS: Background details of the students, their choices of modules and assignment marks were collected as part of the routine course administration. Students' online activities were identified using the student tracking facility within WebCT. Regression models were fitted to explore the association between available explanatory variables and assignment mark. RESULTS: Students choosing online discussions had a higher Core Methods assignment mark (mean 60.8/100) than students choosing face-to-face discussions (54.4); the difference was statistically significant (t=3.13, df=102, p=0.002), although this ignores confounding variables. Among online discussion students, assignment mark was significantly correlated with the numbers of discussion messages read (Kendall's tau(b)=0.22, p=0.050) and posted (Kendall's tau(b)=0.27, p=0.017); among face-to-face discussion students, it was significantly associated with the number of non-discussion hits in WebCT (Kendall's tau(b)=0.19, p=0.036). In regression analysis, choice of discussion method, whether an M.Phil./Ph.D. student, number of non-discussion hits in WebCT, number of online discussion messages read and number posted were associated with assignment mark at the 5% level of significance when taken singly; in combination, only whether an M.Phil./Ph.D. student (p=0.024) and number of non-discussion hits (p=0.045) retained significance. CONCLUSIONS: This study demonstrates that a research methods course can be delivered to postgraduate healthcare students at least as successfully by an entirely online method in which students participate in online discussion as by a blended method in which students accessing web-based teaching material attend face-to-face seminar discussions. Increased online activity was associated with higher assignment marks. The study highlights new opportunities for educational research that arise from the use of virtual learning environments that routinely record the activities of learners and tutors.     

Developing guided self-help for depression using the Medical Research Council complex interventions framework: a description of the modelling phase and results of an exploratory randomised controlled trial

Background

Current guidelines for the management of depression suggest the use of guided self-help for patients with mild to moderate disorders. However, there is little consensus concerning the optimal form and delivery of this intervention. To develop acceptable and effective interventions, a phased process has been proposed, using a modelling phase to examine and develop an intervention prior to preliminary testing in an exploratory trial. This paper (a) describes the modelling phase used to develop a guided self-help intervention for depression in primary care and (b) reports data from an exploratory randomised trial of the intervention.

Methods

A guided self-help intervention was developed following a modelling phase which involved a systematic review, meta synthesis and a consensus process. The intervention was then tested in an exploratory randomised controlled trial by examining (a) fidelity using analysis of taped guided self-help sessions (b) acceptability to patients and professionals through qualitative interviews (c) effectiveness through estimation of the intervention effect size.

Results

Fifty eight patients were recruited to the exploratory trial. Seven professionals and nine patients were interviewed, and 22 tapes of sessions analysed for fidelity. Generally, fidelity to the intervention protocol was high, and the professionals delivered the majority of the specific components (with the exception of the use of feedback). Acceptability to both professionals and patients was also high. The effect size of the intervention on outcomes was small, and in line with previous analyses showing the modest effect of guided self-help in primary care. However, the sample size was small and confidence intervals around the effectiveness estimate were wide.

Conclusion

The general principles of the modelling phase adopted in this study are designed to draw on a range of evidence, potentially providing an intervention that is evidence-based, patient-centred and acceptable to professionals. However, the pilot outcome data did not suggest that the intervention developed was particularly effective. The advantages and disadvantages of the general methods used in the modelling phase are discussed, and possible reasons for the failure to demonstrate a larger effect in this particular case are outlined.     

Young adult attitudes about Alzheimer's disease

The current generation of young adults will be greatly affected by Alzheimer's disease(AD), but little is known about their attitudes toward persons with Alzheimer's disease. The current study assessed attitudes about Alzheimer's disease in young adults with varying levels of contact with the disease. It was hypothesized that participants who had a high level of contact with someone with Alzheimer's disease previously, in the form of a close relationship, would report more positive attitudes than participants with a low level of contact or no contact. Results revealed that participants who had a high level of contact with persons with AD were more willing to make personal sacrifices for Alzheimer's disease than those who had no contact. Younger persons may realize a greater need to support persons with Alzheimer's disease if they have been personally affected by the disease through a close relationship.     

Movement-dependent stroke recovery: a systematic review and meta-analysis of TMS and fMRI evidence

Evidence indicates that experience-dependent cortical plasticity underlies post-stroke motor recovery of the impaired upper extremity. Motor skill learning in neurologically intact individuals is thought to involve the primary motor cortex, and the majority of studies in the animal literature have studied changes in the primary sensorimotor cortex with motor rehabilitation. Whether changes in engagement in the sensorimotor cortex occur in humans after stroke currently is an area of much interest. The present study conducted a meta-analysis on stroke studies examining changes in neural representations following therapy specifically targeting the upper extremity to determine if rehabilitation-related motor recovery is associated with neural plasticity in the sensorimotor cortex of the lesioned hemisphere. Twenty-eight studies investigating upper extremity neural representations (e.g., TMS, fMRI, PET, or SPECT) were identified, and 13 met inclusion criteria as upper extremity intervention training studies. Common outcome variables representing changes in the primary motor and sensorimotor cortices were used in calculating standardized effect sizes for each study. The primary fixed effects model meta-analysis revealed a large overall effect size (ES=0.84, S.D.=0.15, 95% CI=0.76-0.93). Moreover, a fail-safe analysis indicated that 42 null effect studies would be necessary to lower the overall effect size to an insignificant level. These results indicate that neural changes in the sensorimotor cortex of the lesioned hemisphere accompany functional paretic upper extremity motor gains achieved with targeted rehabilitation interventions.     

Large pelvic arteriovenous malformation complicating laparoscopic radical prostatectomy

Pelvic arteriovenous malformations (AVM) are rare, usually congenital, lesions, which can pose significant difficulties for pelvic surgeons. We present a case of an AVM complicating laparoscopic radical prostatectomy. Unexpected failure of preoperative control led to significant intraoperative difficulty. The advantages of an antegrade approach and optimal magnification afforded by the laparoscopic approach led to successful completion of the operation with minimal morbidity.