Existing guidelines on overviews of reviews and umbrella reviews recommend an assessment of the certainty of evidence but provide limited guidance on how to apply GRADE to such a complex evidence synthesis. We present one approach to applying GRADE to an overview of reviews developed using general principles derived from current GRADE guidelines.

The methods were developed in an iterative and exploratory fashion following discussion with 11 methodologists and health services researchers. Key principles were distilled on the five GRADE domains (risk of bias, inconsistency, imprecision, indirectness, and publication bias) from the relevant GRADE guidelines, particularly those on test accuracy.

A ‘general principles’ approach of applying the five domains of GRADE to an overview of reviews and arriving at an overall summary judgment for outcomes was developed. These methods were successfully applied to an overview of reviews on 18F-prostate specific membrane antigen positron emission tomography and computed tomography in the staging of patients with high-risk or recurrent prostate cancer.

Our approach distilled key principles from relevant GRADE guidelines and allowed us to apply GRADE to a complex body of evidence. Such an approach may be of interest to other researchers working on overviews of reviews or umbrella reviews.

Volumetric atrophy and microstructural alterations in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, no study to date has jointly investigated concomitant microstructural and volumetric changes of the hippocampus in dementia with Lewy bodies (DLB).

A total of 84 subjects (23 MCI, 17 DLB, 14 AD, and 30 healthy controls) were recruited for a multi-modal imaging (3T MRI and DTI) study that included neuropsychological evaluation. Freesurfer was used to segment the total hippocampus and delineate its subfields. The hippocampal segmentations were co-registered to the mean diffusivity (MD) and fractional anisotropy (FA) maps obtained from the DTI images.

Both AD and MCI groups showed significantly smaller hippocampal volumes compared to DLB and controls, predominantly in the CA1 and subiculum subfields. Compared to controls, hippocampal MD was elevated in AD, but not in MCI. DLB was characterized by both volumetric and microstructural preservation of the hippocampus. In MCI, higher hippocampal MD was associated with greater atrophy of the hippocampus and CA1 region. Hippocampal volume was a stronger predictor of memory scores compared to MD within the MCI group.

Through a multi-modal integration, we report novel evidence that the hippocampus in DLB is characterized by both macrostructural and microstructural preservation. Contrary to recent suggestions, our findings do not support the view that DTI measurements of the hippocampus are superior to volumetric changes in characterizing group differences, particularly between MCI and controls.

Poor weight gain is common in infants after Stage I Norwood operation and can negatively impact outcomes.

The purpose of this study was to examine the impact of feeding strategy on interstage weight gain.

In a multi-centre study, 158 infants discharged following the Norwood operation were enrolled prospectively. Weight and feeding data were obtained at 2-week intervals. Differences between feeding regimens in average daily weight gain and change in weight-for-age z-score between Stage I discharge and Stage II surgery were examined.

Discharge feeding regimens were oral only in 52%, oral with tube supplementation in 33%, and by nasogastric/gastrostomy tube only in 15%. There were significant differences in the average daily interstage weight gain among the feeding groups – oral only 25.0 grams per day, oral/tube 21.4 grams per day, and tube only 22.3 grams per day – p = 0.019. Tube-only-fed infants were significantly older at Stage II (p = 0.004) and had a significantly greater change in weight-for-age z-score (p = 0.007). The overall rate of weight gain was 16–32 grams per day, similar to infant norms. The rate of weight gain declined over time, with earlier decline observed for oral- and oral/tube-fed infants (less than 15 grams per day at 5.4 months) in comparison with tube-only-fed infants (less than 15 grams per day at 8.6 months).

Following Stage I Norwood, infants discharged on oral feeding had better average daily weight gain than infants with tube-assisted feeding. The overall weight gain was within the normal limits in all feeding groups, but the rate of weight gain decreased over time, with an earlier decline in infants fed orally.

To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital.

Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistant Enterococcus faecium despite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group; (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection of vanA and vanB resistance genes; (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts; (4) environmental screening and increased cleaning; (5) electronic flagging of medical records of contacts; and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin).

A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistant E. faecium. Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregat-ed patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of $2.7 million (Australian dollars).

Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.

An age-related dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory.

To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM–III–R Major Depression.

Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI.

An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease.

T2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM–III–R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0–3 scale by two radiologists blind to clinical diagnosis.

After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML.

An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.