Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial

Objectives To determine whether (i) supplementation of oral 100 000 iu of vitamin D₃ (cholecalciferol) along with antibiotics will reduce the duration of illness in children with pneumonia; (ii) supplementation will reduce the risk of repeat episodes. Methods Double‐blind individually randomised placebo‐controlled trial in an inner‐city hospital in Kabul, of 453 children aged 1–36 months, diagnosed with non‐severe or severe pneumonia at the outpatient clinic. Children with rickets, other concurrent severe diseases, very severe pneumonia or wheeze, were excluded. Children were given vitamin D₃ or placebo drops additional to routine pneumonia treatment. Results Two hundred and twenty‐four children received vitamin D_3; and 229 received placebo. There was no significant difference in the mean number of days to recovery between the vitamin D₃ (4.74 days; SD 2.22) and placebo arms (4.98 days; SD 2.89; P = 0.17). The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention (92/204; 45%) than the placebo group [122/211; (58%; relative risk 0.78; 95% CI 0.64, 0.94; P = 0.01]. Children in the vitamin D₃ group survived longer without experiencing a repeat episode (72 days vs. 59 days; HR 0.71; 95% CI 0.53–0.95; P = 0.02). Conclusion A single high‐dose oral vitamin D₃ supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia.     

The BELFRAIL (BFC80+) study: a population-based prospective cohort study of the very elderly in Belgium

Background

Reminiscence is the systematic use of memories and recollections to strengthen self-identity and self-worth. The study aim was to investigate the consequences for nursing home residents and staff of integrating reminiscence into daily nursing care.

Methods

In this randomised study, ten nursing homes were matched into two groups on the basis of location, type and size. In the period August 2006 - August 2007, staff in the Intervention Group were trained and supported in the use of reminiscence, involving individual and group sessions with residents as well as reminiscence boxes, posters and exhibitions. At baseline and again 6 and 12 months after the intervention start, data were collected on residents' cognitive level, agitated behaviour, general functioning and proxy-assessed quality of life, as well as on staff well-being and job satisfaction. Mixed linear modelling was used to analyse differences in outcome between the intervention and control groups.

Results

Project drop-out rates were 32% for residents and 38% for nursing staff. Most staff in the Intervention Group considered reminiscence a useful tool that improved their communication with residents, and that they would recommend to other nursing homes. There were no significant differences between residents in the Intervention and the Control Group in cognitive level, agitated behaviour or general functioning. Residents in the Intervention Group showed significant higher score at 6 months in quality of life subscale 'Response to surroundings', but there was no significant difference at 12 months. Positive effects of reminiscence were observed for all staff outcome measures, the only exception being SF-12 self-rated physical health. At 6 months after start of reminiscence, staff in the Intervention Group had significantly better scores than those in the Control Group for Personal accomplishment, Emotional exhaustion, Depersonalisation, 'Attitude towards individual contact with residents' and SF-12 self-rated mental health. At 12 months after start of reminiscence, staff in the Intervention Group had significantly better scores than those in the Control Group for Emotional exhaustion and 'Professional role and development'.

Conclusions

The use of reminiscence appeared to have little long-term effect on the nursing home residents. Nursing staff in the Intervention Group experienced greater satisfaction with professional roles and developed a more positive view of the residents. International Standard Randomised Controlled Trial Number Register: ISRCTN90253170.     

Cognitive complaints after mild traumatic brain injury: things are not always what they seem

OBJECTIVE: To compare nonreferred, emergency department (ED)-admitted mild traumatic brain injury (MTBI) patients with and without self-reported cognitive complaints on (1) demographic variables and injury characteristics; (2) neuropsychological test performance; (3) 12-day self-monitoring of perceived cognitive problems; and (4) emotional distress, physical functioning, and personality. METHODS: (Neuro)psychological assessment was carried out 6 months post-injury in 79 patients out of a cohort of 618 consecutive MTBI patients aged 18-60, who attended the ED of our level I trauma centre. Cognitive complaints were assessed with the Rivermead Postconcussional Symptoms Questionnaire (RPSQ). In addition, patients monitored concentration problems and forgetfulness during 12 consecutive days. RESULTS: Self-reported cognitive complaints were reported by 39% of the patients. These complaints were strongly related to lower educational levels, emotional distress, personality, and poorer physical functioning (especially fatigue) but not to injury characteristics. Severity of self-reported cognitive complaints was neither associated with the patients' daily observations of cognitive problems nor with outcome on a range of neuropsychological tests. CONCLUSION: Self-reported cognitive complaints were more strongly related to premorbid traits and physical and emotional state factors than to actual cognitive impairments. In line with previous work, this suggests that treatment of emotional distress and fatigue may also reduce cognitive complaints. Cognitive outcome assessment of symptomatic MTBI patients should not be restricted to checklist ratings only, but also include a (neuro)psychological screening. In addition, daily monitoring of complaints is a useful method to gather information about the frequency and pattern of cognitive problems in daily life.     

The non-gastric H,K-ATPase as a tool to study the ouabain-binding site in Na,K-ATPase

Based on studies with chimeras between (non-)gastric H,K-ATPase and Na,K-ATPase, a model for the ouabain binding site has recently been presented (Qiu et al. J.Biol.Chem. 280 (2005) 32349). In this model, hydrogen bonds between specific amino acid residues of Na,K-ATPase and hydroxyl groups of ouabain play a crucial role. In the present study, a series of ouabain analogues were tested on baculovirus-expressed Na,K-ATPase and an ouabain-sensitive mutant of non-gastric H,K-ATPase (D312E/ S319G/ A778P/ I795L/ F802C). For each analogue, the results obtained by measuring ATPase inhibition and [³H]ouabain replacement agreed rather well. In Na,K-ATPase, strophanthidin had a 7–10 times higher and digoxin a 4–12 times lower affinity than ouabain. The results of the non-gastric H,K-ATPase mutant were rather similar to that of Na,K-ATPase with exception of dihydro-ouabain that showed a much lower affinity with the non-gastric H,K-ATPase mutant. Docking studies showed that all analogues bind to the same pocket in Na,K-ATPase. However, the amino acids to which hydrogen bonds were formed differed and depended on the availability of hydroxyl or keto groups in the ouabain analogues.     

Sensitivity of the individual items of the Hamilton depression rating scale to response and its consequences for the assessment of efficacy

The Hamilton depression rating scale (HAM-D(17)) has been the gold standard in depression trials since its introduction in 1960 by Max Hamilton. However, several authors have shown that the HAM-D(17) is multi-dimensional and that subscales of the HAM-D(17) outperform the total scale. In the current study, we assess the sensitivity of the individual HAM-D(17) items in differentiating responders from non-responders over the typical treatment period used in clinical efficacy trials. Based on data from randomised, placebo-controlled trials with paroxetine, a graphical analysis and a statistical analysis were performed to identify the items that are most sensitive to the rate and extent of response irrespective of treatment. From these analyses, two subscales consisting of seven items each were derived and compared to the Bech and Maier and Philip subscales using a linear mixed-effects modelling approach for repeated measures. The evaluation of two clinical trials revealed endpoint sensitivity comparable to the existing subscales. Using a bootstrap technique, we show that the subscales consistently yield higher statistical power compared to the HAM-D(17), although no subscale consistently outperforms the others. In conclusion, this study provides further evidence that not all items of the HAM-D(17) scale are equally sensitive to detect responding patients in a clinical trial. A HAM-D(7) subscale with higher sensitivity to drug effect is proposed consisting of the HAM-D(6) and the suicide item. This response-based subscale increases signal-to-noise ratio and could reduce failure rate in efficacy trials with antidepressant drugs.     

Evaluation of treatment response in depression studies using a Bayesian parametric cure rate model

Efficacy trials with antidepressant drugs often fail to show significant treatment effect even though efficacious treatments are investigated. This failure can, amongst other factors, be attributed to the lack of sensitivity of the statistical method as well as of the endpoints to pharmacological activity. For regulatory purposes the most widely used efficacy endpoint is still the mean change in HAM-D score at the end of the study, despite evidence from literature showing that the HAM-D scale might not be a sensitive tool to assess drug effect and that changes from baseline at the end of treatment may not reflect the extent of response. In the current study, we evaluate the prospect of applying a Bayesian parametric cure rate model (CRM) to analyse antidepressant effect in efficacy trials with paroxetine. The model is based on a survival approach, which allows for a fraction of surviving patients indefinitely after completion of treatment. Data was extracted from GlaxoSmithKline's clinical databases. Response was defined as a 50% change from baseline HAM-D at any assessment time after start of therapy. Survival times were described by a log-normal distribution and drug effect was parameterised as a covariate on the fraction of non-responders. The model was able to fit the data from different studies accurately and results show that response to treatment does not lag for two weeks, as is mythically believed. In conclusion, we demonstrate how parameterisation of a survival model can be used to characterise treatment response in depression trials. The method contrasts with the long-established snapshot on changes from baseline, as it incorporates the time course of response throughout treatment.