Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Dietary and serum tyrosine, white matter microstructure and inter-individual variability in executive functions in overweight adults: Relation to sex/gender and age.

Tyrosine (tyr), the precursor of the neurotransmitter dopamine, is known to modulate cognitive functions including executive attention. Tyr supplementation is suggested to influence dopamine-modulated cognitive performance. However, results are inconclusive regarding the presence or strength and also the direction of the association between tyr and cognitive function. This pre-registered cross-sectional analysis investigates whether diet-associated serum tyr relates to executive attention performance, and whether this relationship is moderated by differences in white matter microstructure. 59 healthy, overweight, young to middle-aged adults (20 female sex/gender group, 28.3 ± 6.6 years, BMI: 27.3 ± 1.5 kg/m2) drawn from a longitudinal study reported dietary habits, donated blood and completed diffusion-weighted brain magnetic resonance imaging and the attention network test. Main analyses were performed using linear regressions and non-parametric voxel-wise inference testing. Confirmatory analyses did neither support an association between dietary and serum tyr nor a relationship between relative serum tyr/large neutral amino acids (LNAA) levels or white matter microstructure and executive attention performance. However, exploratory analyses revealed higher tyr intake, higher serum tyr and better executive attention performance in the male sex/gender group. In addition, older age was associated with higher dietary tyr intake and lower fractional anisotropy in a widespread cluster across the brain. Finally, a positive association between relative serum tyr/LNAA level and executive attention performance was found in the male sex/gender group when accounting for age effects. Our analysis advances the field of dopamine-modulated cognitive functions by revealing sex/gender and age differences which might be diet-related. Longitudinal or intervention studies and larger sample sizes are needed to provide more reliable evidence for links between tyr and executive attention.

Examining the effectiveness of place-based interventions to improve public health and reduce health inequalities: an umbrella review.

BACKGROUND: Locally delivered, place-based public health interventions are receiving increasing attention as a way of improving health and reducing inequalities. However, there is limited evidence on their effectiveness. This umbrella review synthesises systematic review evidence of the health and health inequalities impacts of locally delivered place-based interventions across three elements of place and health: the physical, social, and economic environments. METHODS: Systematic review methodology was used to identify recent published systematic reviews of the effectiveness of place-based interventions on health and health inequalities (PROGRESS+) in high-income countries. Nine databases were searched from 1st January 2008 to 1st March 2020. The quality of the included articles was determined using the Revised Assessment of Multiple Systematic Reviews tool (R-AMSTAR). RESULTS: Thirteen systematic reviews were identified - reporting 51 unique primary studies. Fifty of these studies reported on interventions that changed the physical environment and one reported on changes to the economic environment. Only one primary study reported cost-effectiveness data. No reviews were identified that assessed the impact of social interventions. Given heterogeneity and quality issues, we found tentative evidence that the provision of housing/home modifications, improving the public realm, parks and playgrounds, supermarkets, transport, cycle lanes, walking routes, and outdoor gyms - can all have positive impacts on health outcomes - particularly physical activity. However, as no studies reported an assessment of variation in PROGRESS+ factors, the effect of these interventions on health inequalities remains unclear. CONCLUSIONS: Place-based interventions can be effective at improving physical health, health behaviours and social determinants of health outcomes. High agentic interventions indicate greater improvements for those living in greater proximity to the intervention, which may suggest that in order for interventions to reduce inequalities, they should be implemented at a scale commensurate with the level of disadvantage. Future research needs to ensure equity data is collected, as this is severely lacking and impeding progress on identifying interventions that are effective in reducing health inequalities. TRIAL REGISTRATION: PROSPERO CRD42019158309.

The age-dependent relationship between resting heart rate variability and functional brain connectivity.

Resting heart rate variability (HRV), an index of parasympathetic cardioregulation and an individual trait marker related to mental and physical health, decreases with age. Previous studies have associated resting HRV with structural and functional properties of the brain - mainly in cortical midline and limbic structures. We hypothesized that aging affects the relationship between resting HRV and brain structure and function. In 388 healthy subjects of three age groups (140 younger: 26.0 ±â€¯4.2 years, 119 middle-aged: 46.3 ±â€¯6.2 years, 129 older: 66.9 ±â€¯4.7 years), gray matter volume (GMV, voxel-based morphometry) and resting state functional connectivity (eigenvector centrality mapping and exploratory seed-based functional connectivity) were related to resting HRV, measured as the root mean square of successive differences (RMSSD). Confirming previous findings, resting HRV decreased with age. For HRV-related GMV, there were no statistically significant differences between the age groups, nor similarities across all age groups. In whole-brain functional connectivity analyses, we found an age-dependent association between resting HRV and eigenvector centrality in the bilateral ventromedial prefrontal cortex (vmPFC), driven by the younger adults. Across all age groups, HRV was positively correlated with network centrality in the bilateral posterior cingulate cortex. Seed-based functional connectivity analysis using the vmPFC cluster revealed an HRV-related cortico-cerebellar network in younger but not in middle-aged or older adults. Our results indicate that the decrease of HRV with age is accompanied by changes in functional connectivity along the cortical midline. This extends our knowledge of brain-body interactions and their changes over the lifespan.

The Cochrane 2018 Review on Brief Interventions in Primary Care for Hazardous and Harmful Alcohol Consumption: A Distillation for Clinicians and Policy Makers.

AIMS: An updated Cochrane systematic review assessed effectiveness of screening and brief intervention to reduce hazardous or harmful alcohol consumption in general practice or emergency care settings. This paper summarises the implications of the review for clinicians. METHODS: Cochrane methods were followed. Reporting accords with PRISMA guidance. We searched multiple resources to September 2017, seeking randomised controlled trials of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. Brief intervention was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 min. Our primary outcome was alcohol consumption, measured as or convertible to grams per week. We conducted meta-analyses to assess change in consumption, and subgroup analyses to explore the impact of participant and intervention characteristics. RESULTS: We included 69 studies, of which 42 were added for this update. Most studies (88%) compared brief intervention to control. The primary meta-analysis included 34 studies and provided moderate-quality evidence that brief intervention reduced consumption compared to control after one year (mean difference -20 g/wk, 95% confidence interval -28 to -12). Subgroup analysis showed a similar effect for men and women. CONCLUSIONS: Brief interventions can reduce harmful and hazardous alcohol consumption in men and women. Short, advice-based interventions may be as effective as extended, counselling-based interventions for patients with harmful levels of alcohol use who are presenting for the first time in a primary care setting.

Lumbar lordosis and sacral slope in lumbar spinal stenosis: standard values and measurement accuracy.

STUDY DESIGN: Radiological study. PURPOSE: To asses standard values, intra- and interobserver reliability and reproducibility of sacral slope (SS) and lumbar lordosis (LL) and the correlation of these parameters in patients with lumbar spinal stenosis (LSS). METHODS: Anteroposterior and lateral X-rays of the lumbar spine of 102 patients with LSS were included in this retrospective, radiologic study. Measurements of SS and LL were carried out by five examiners. Intraobserver correlation and correlation between LL and SS were calculated with Pearson's r linear correlation coefficient and intraclass correlation coefficients (ICC) were calculated for inter- and intraobserver reliability. In addition, patients were examined in subgroups with respect to previous surgery and the current therapy. RESULTS: Lumbar lordosis averaged 45.6° (range 2.5°-74.9°; SD 14.2°), intraobserver correlation was between Pearson r = 0.93 and 0.98. The measurement of SS averaged 35.3° (range 13.8°-66.9°; SD 9.6°), intraobserver correlation was between Pearson r = 0.89 and 0.96. Intraobserver reliability ranged from 0.966 to 0.992 ICC in LL measurements and 0.944-0.983 ICC in SS measurements. There was an interobserver reliability ICC of 0.944 in LL and 0.990 in SS. Correlation between LL and SS averaged r = 0.79. No statistically significant differences were observed between the analyzed subgroups. CONCLUSION: Manual measurement of LL and SS in patients with LSS on lateral radiographs is easily performed with excellent intra- and interobserver reliability. Correlation between LL and SS is very high. Differences between patients with and without previous decompression were not statistically significant.

Percutaneous interspinous spacer versus open decompression: a 2-year follow-up of clinical outcome and quality of life.

PURPOSE: Percutaneous interspinous stand-alone spacers offer a simple and effective technique to treat lumbar spinal stenosis with neurogenic claudication. Nonetheless, open decompressive surgery remains the standard of care. This study compares the effectiveness of both techniques and the validity of percutaneous interspinous spacer use. METHODS: Forty-five patients were included in this open prospective non-randomized study, and treated either with percutaneous interspinous stand-alone spacers (Aperius(®)) or bilateral open microsurgical decompression at L3/4 or L4/5. Patient data, operative data, COMI, SF-36, PCS and MCS, ODI, and walking distance were collected 6 weeks, 3, 6, 9, 12, and 24 months post-surgery. RESULTS: Group 1 (n = 12) underwent spacer implantation, group 2 (n = 33) open decompression. Five patients from group 1 required implant removal and open decompression during follow-up (FU); one patient was lost to FU. From group 2, seven patients were lost to FU. Remaining patients were assessed as above. After 2 years, back pain, leg pain, ODI, and quality of life improved significantly for group 2. Remaining group 1 patients (n = 6) reported worse results. Walking distance improved for both groups. CONCLUSION: Decompression proved superior to percutaneous stand-alone spacer implantation in our two observational cohorts. Therapeutic failure was too high for interspinous spacers.

Evaluating the translation of implementation science to clinical artificial intelligence: a bibliometric study of qualitative research.

Introduction: Whilst a theoretical basis for implementation research is seen as advantageous, there is little clarity over if and how the application of theories, models or frameworks (TMF) impact implementation outcomes. Clinical artificial intelligence (AI) continues to receive multi-stakeholder interest and investment, yet a significant implementation gap remains. This bibliometric study aims to measure and characterize TMF application in qualitative clinical AI research to identify opportunities to improve research practice and its impact on clinical AI implementation. Methods: Qualitative research of stakeholder perspectives on clinical AI published between January 2014 and October 2022 was systematically identified. Eligible studies were characterized by their publication type, clinical and geographical context, type of clinical AI studied, data collection method, participants and application of any TMF. Each TMF applied by eligible studies, its justification and mode of application was characterized. Results: Of 202 eligible studies, 70 (34.7%) applied a TMF. There was an 8-fold increase in the number of publications between 2014 and 2022 but no significant increase in the proportion applying TMFs. Of the 50 TMFs applied, 40 (80%) were only applied once, with the Technology Acceptance Model applied most frequently (n = 9). Seven TMFs were novel contributions embedded within an eligible study. A minority of studies justified TMF application (n = 51,58.6%) and it was uncommon to discuss an alternative TMF or the limitations of the one selected (n = 11,12.6%). The most common way in which a TMF was applied in eligible studies was data analysis (n = 44,50.6%). Implementation guidelines or tools were explicitly referenced by 2 reports (1.0%). Conclusion: TMFs have not been commonly applied in qualitative research of clinical AI. When TMFs have been applied there has been (i) little consensus on TMF selection (ii) limited description of selection rationale and (iii) lack of clarity over how TMFs inform research. We consider this to represent an opportunity to improve implementation science's translation to clinical AI research and clinical AI into practice by promoting the rigor and frequency of TMF application. We recommend that the finite resources of the implementation science community are diverted toward increasing accessibility and engagement with theory informed practices. The considered application of theories, models and frameworks (TMF) are thought to contribute to the impact of implementation science on the translation of innovations into real-world care. The frequency and nature of TMF use are yet to be described within digital health innovations, including the prominent field of clinical AI. A well-known implementation gap, coined as the "AI chasm" continues to limit the impact of clinical AI on real-world care. From this bibliometric study of the frequency and quality of TMF use within qualitative clinical AI research, we found that TMFs are usually not applied, their selection is highly varied between studies and there is not often a convincing rationale for their selection. Promoting the rigor and frequency of TMF use appears to present an opportunity to improve the translation of clinical AI into practice.

[Imaging of pneumonia]. / Bildgebende Diagnostik von Pneumonien.

Pneumonia represents a disease with significant epidemiological, clinical and also economical relevance. Diagnostic imaging is important for detection, differentiation and follow up of pneumonic infiltration. However morphology of pulmonary infiltration is unspecific, even with computed tomography (CT). Therefore determination of the underlying agent with imaging is generally limited and non infectious differential diagnosis has to be considered. Knowledge of special manifestations, distribution patterns and differential diagnoses of pneumonic infiltrations and consideration of clinical aspects is essential to narrow differential diagnosis and spectrum of infectious agents. CT of the chest is particularly important in opportunistic infections and in patients under intensive medical treatment.

Prediction of lymph node metastases in NSCLC. Three dimensional anatomical parameters do not substitute FDG-PET-CT.

PURPOSE: To distinguish between benign and malignant mediastinal lymph nodes in patients with NSCLC by comparing 2D and semi-automated 3D measurements in FDG-PET-CT. PATIENTS, MATERIAL, METHODS: FDG-PET-CT was performed in 46 patients prior to therapy. 299 mediastinal lymph-nodes were evaluated independently by two radiologists, both manually and by semi-automatic segmentation software. Longest-axial-diameter (LAD), shortest-axial-diameter (SAD), maximal-3D-diameter, elongation and volume were obtained. FDG-PET-CT and clinical/FDG-PET-CT follow up examinations and/or histology served as the reference standard. Statistical analysis encompassed intra-class-correlation-coefficients and receiver-operator-characteristics-curves (ROC). RESULTS: The standard of reference revealed involvement in 87 (29%) of 299 lymph nodes. Manually and semi-automatically measured 2D parameters (LAD and SAD) showed a good correlation with mean intraclass coefficients of .80 and .72, respectively. Semi-automated prediction revealed the highest areas-under-the-ROC-curve for volume (.75, 95%CI: .69-81) and SAD (.75, 95%CI: .70-.81). AUC for LAD and maximal-3D diameter were about .68. Substantially lower accuracies were found for elongation (.57, 95%CI: .50-.64). CONCLUSION: Optimized semi-automated three dimensional parameters by CT cannot approximate reported data on FDG-PET-CT for lymph node assessment in NSCLC. SAD remains the most accurate and at the same time simple to achieve anatomical criterion for definition of NSCLC target lesions.

Relationship between pubertal testicular ultrasonographic evaluation and future reproductive performance potential in Piétrain boars.

New ways of predicting sperm quality and output performance in young artificial insemination (AI) boars are important for breeding companies to ensure that the pubertal boars delivered to the AI studs have a high chance of meeting minimum quality standards to be used for insemination and therewith dissemination of desirable characteristics. The aim of the current study was to characterize the testicular development of 218 pubertal Piétrain boars (Line 408, Pig Improvement Company) to identify traits with predictable characteristics relative to their sperm quality as an adult AI boar. Scrotum, testes and epididymis were examined ultrasonographically at day (d) 100 (on-test) and 170 (off-test) followed by a computer-assisted grayscale analysis (GSA). Over the test period, paired testicular volume increased 7.3-fold from 22.7 ± 10.8 cm3 to 166.6 ± 62.2 cm3. The right testis was significantly (P = 0.014) larger than the left one at the off-test. Based on the sperm quality (ejaculate volume, sperm concentration, total sperm number, morphologically abnormal sperm and total sperm motility at day 3 of semen storage), 82.11% (n = 179) of the boars were classified as "productive" boars. These boars had a significantly (P = 0.039) larger paired testicular volume than "non-productive" boars (45.9 ± 19.9 cm3vs. 38.5 ± 12.6 cm3) at the on-test. For the right testis at on-test, significant differences for the standard deviation of mean gray value (P = 0.022), area under the curve (P = 0.004) and mean gradient value (GRAD, P = 0.030) regarding the future sperm production capacity (SPC) were shown. At off-test, there was a significant difference for minimum gray value (MIN GV, P = 0.003) and mean gray value (P = 0.001) related to SPC. To find SPC related cut-off values for GSA data, a two segmental non-linear regression analysis was carried out indicating breakpoints for GRAD ≥12 and MIN GV ≥ 40 for boars with low SPC. Off-test boars with MIN GV ≥ 40 showed a 2.4 higher risk to display low SPC (Odds ratio = 2.4 [1.1, 5.4]; P = 0.024). The results may enable breeding companies to include new sperm quality associated traits in their boar testing and selection programs.

Fluid resuscitation after severe trauma injury : U-shaped associations between tetrastarch dose and survival time or frequency of acute kidney failure.

BACKGROUND: Using tetrastarch for fluid resuscitation after a severe trauma injury may increase risks of death and acute kidney injury. The importance of tetrastarch dose, however, is unknown. METHODS: A retrospective observational study was performed in two trauma centres using data on type and amount of fluids (balanced crystalloids or tetrastarch) used for pre- and acute in-hospital shock management. We evaluate independent associations between the relative and absolute volumes of tetrastarch and 90-day survival time or the frequency of severe acute kidney failure (AKF). RESULTS: We studied 271 patients who had sustained a severe blunt trauma injury (average predicted mortality according to the Revised Injury Severity Classification Score (RISC) 15.1 ± 1.4% [mean, standard deviation]), and who had required more than 2 days of intensive care therapy. In all, 75.3% of patients had received tetrastarch with a crystalloid/colloid ratio of 2.93 ± 2.60. The 90-day mortality was 11.1%, and 7.8% of the patients developed severe AKF. After adjusting for confounders, we found a U-shaped, nonlinear association between absolute or relative volumes of tetrastarch and survival time (p = 0.003 and 0.025, respectively). Optimal relative volumes of tetrastarch approximately ranged from 20 to 30% of total fluids. Giving less than about 1000 ml, or more than about 2000 ml tetrastarch was significantly associated with an increased risk of developing severe AKF (p = 0.023). CONCLUSIONS: There was a complex U­shaped association between the tetrastarch dose and morbidity/mortality of patients after a severe trauma injury. The optimal crystalloid/tetrastarch ratio for acute shock management appears to range from about 2.5 to 4.0.

Serum BDNF levels correlate with regional cortical thickness in minor depression: a pilot study.

Serum brain-derived neurotrophic factor (BDNF) reflects state changes in mood disorders. But its relation to brain changes in depression has rarely been investigated in humans. We assessed the association between serum BDNF, cortical thickness, or gray matter volume in 20 subjects with a minor depressive episode and 40 matched healthy subjects. Serum BDNF positively correlated with cortical thickness and volume in multiple brain regions in the minor depression group: the bilateral medial orbitofrontal cortex and rostral anterior cingulate cortex, left insula, and cingulum, right superior frontal gyrus, and other regions-regions typically affected by major depression. Interestingly, these correlations were driven by subjects with first episode depression. There was no significant association between these imaging parameters and serum BDNF in the healthy control group. Interaction analyses supported this finding. Our findings point to a specific association between serum BDNF and magnetic resonance imaging parameters in first-episode minor depression in a region- and condition-dependent manner. A positive correlation between serum BDNF and structural gray matter estimates was most consistently observed for cortical thickness. We discuss why cortical thickness should be preferred to volumetric estimates for such analyses in future studies. Results of our pilot study have to be proven in future larger-scale studies yielding higher statistical power.

Higher body mass index is linked to altered hypothalamic microstructure.

Animal studies suggest that obesity-related diets induce structural changes in the hypothalamus, a key brain area involved in energy homeostasis. Whether this translates to humans is however largely unknown. Using a novel multimodal approach with manual segmentation, we here show that a higher body mass index (BMI) selectively predicted higher proton diffusivity within the hypothalamus, indicative of compromised microstructure in the underlying tissue, in a well-characterized population-based cohort (n1 = 338, 48% females, age 21-78 years, BMI 18-43 kg/m²). Results were independent from confounders and confirmed in another independent sample (n2 = 236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. Our findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.

Effectiveness of brief alcohol interventions in primary care populations.

BACKGROUND: Many trials reported that brief interventions are effective in reducing excessive drinking. However, some trials have been criticised for being clinically unrepresentative and unable to inform clinical practice. OBJECTIVES: To assess the effectiveness of brief intervention, delivered in general practice or based primary care, to reduce alcohol consumption SEARCH STRATEGY: We searched the Cochrane Drug and Alcohol Group specialised register (February 2006), MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006), CINAHL (1982 to February 2006), PsycINFO (1840 to February 2006), Science Citation Index (1970 to February 2006), Social Science Citation Index (1970 to February 2006), Alcohol and Alcohol Problems Science Database (1972 to 2003), reference lists of articles. SELECTION CRITERIA: Randomised controlled trials, patients presenting to primary care not specifically for alcohol treatment; brief intervention of up to four sessions. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, sub-group, sensitivity analyses, and meta-regression were conducted. MAIN RESULTS: The meta-analysis included 21 RCTs (7,286 participants), showing that participants receiving brief intervention reduced their alcohol consumption compared to the control group (mean difference: -41 grams/week, 95% CI: -57 to -25), although there was substantial heterogeneity between trials (I2 = 52%). Sub-group analysis (8 studies, 2307 participants) confirmed the benefit of brief intervention in men (mean difference: -57 grams/week, 95% CI: -89 to -25, I2 = 56%), but not in women (mean difference: -10 grams/week, 95% CI: -48 to 29, I2 = 45%). Meta-regression showed a non-significant trend of an increased reduction in alcohol consumption of 1.1, 95%CI: -0.05 to 2.2 grams/week, p=0.06, for each extra minute of treatment exposure, but no relationship between the reduction in alcohol consumption and the efficacy score of the trial. Extended intervention when compared with brief intervention was associated with a non-significantly greater reduction in alcohol consumption (mean difference = -28, 95%CI: -62 to 6 grams/week, I2 = 0%) AUTHORS' CONCLUSIONS: Brief interventions consistently produced reductions in alcohol consumption. When data were available by gender, the effect was clear in men at one year of follow up, but unproven in women. Longer duration of counselling probably has little additional effect. The lack of differences in outcomes between efficacy and effectiveness trials suggests that the current literature had clear relevance to routine primary care. Future trials should focus on women and on delineating the most effective components of interventions.

A systematic literature review of the effectiveness of non-pharmacological interventions to prevent wandering in dementia and evaluation of the ethical implications and acceptability of their use.

OBJECTIVES: To determine the effectiveness and cost-effectiveness of non-pharmacological interventions (excluding subjective barriers) in the prevention of wandering in people with dementia, in comparison with usual care, and to evaluate through the review and a qualitative study the acceptability to stakeholders of such interventions and identify ethical issues associated with their use. DATA SOURCES: Major electronic databases were searched up until 31 March 2005. Specialists in the field. REVIEW METHODS: Selected studies were assessed and analysed. The results of two of the efficacy studies that used similar interventions, designs and outcome measures were pooled in a meta-analysis; results for other studies which reported standard deviations were presented in a forest plot. Owing to a lack of cost-effectiveness data, a modelling exercise could not be performed. Four focus groups were carried out with relevant stakeholders (n = 19) including people with dementia and formal and lay carers to explore ethical and acceptability issues in greater depth. Transcripts were coded independently by two reviewers to develop a coding frame. Analysis was via a thematic framework approach. RESULTS: Ten studies met the inclusion criteria (multi-sensory environment, three; music therapy, one; exercise, one; special care units, two; aromatherapy, two; behavioural intervention, one). There was no robust evidence to recommend any non-pharmacological intervention to reduce wandering in dementia. There was some evidence, albeit of poor quality, for the effectiveness of exercise and multi-sensory environment. There were no relevant studies to determine the cost-effectiveness of the interventions. Findings from the narrative review and focus groups on acceptability and ethical issues were comparable. Exercise and distraction therapies were the most acceptable interventions and raised no ethical concerns. All other interventions were considered acceptable except for physical restraints, which were considered unacceptable. Considerable ethical concerns exist with the use of electronic tagging and tracking devices and physical barriers. Existing literature ignores the perspectives of people with dementia. The small number of participants with dementia expressed caution regarding the use of unfamiliar technology. Balancing risk and risk assessment was an important theme for all carers in the management of wandering. CONCLUSIONS: There is no robust evidence so far to recommend the use of any non-pharmacological intervention to reduce or prevent wandering in people with dementia. High-quality studies, preferably randomised controlled trials, are needed to determine the clinical and cost-effectiveness of non-pharmacological interventions that allow safe wandering and are considered practically and ethically acceptable by carers and people with dementia. Large-scale, long-term cohort studies are needed to evaluate the morbidity and mortality associated with wandering in dementia for people both in the community and in residential care. Such data would inform future long-term cost-effectiveness studies.

Potassium supplementation for the management of primary hypertension in adults.

BACKGROUND: Epidemiological evidence on the effects of potassium on blood pressure is inconsistent. OBJECTIVES: To evaluate the effects of potassium supplementation on health outcomes and blood pressure in people with elevated blood pressure. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. SELECTION CRITERIA: Inclusion criteria were: 1) RCTs of a parallel or crossover design comparing oral potassium supplements with placebo, no treatment, or usual care; 2) treatment and follow-up >=8 weeks; 3) participants over 18 years, with raised systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >=85 mmHg); 4) SBP and DBP reported at end of follow-up. We excluded trials where: participants were pregnant; received antihypertensive medication which changed during the study; or potassium supplementation was combined with other interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: Six RCT's (n=483), with eight to 16 weeks follow-up, met our inclusion criteria. Meta-analysis of five trials (n=425) with adequate data indicated that potassium supplementation compared to control resulted in a large but statistically non-significant reductions in SBP (mean difference: -11.2, 95% CI: -25.2 to 2.7) and DBP (mean difference: -5.0, 95% CI: -12.5 to 2.4). The substantial heterogeneity between trials was not explained by potassium dose, quality of trials or baseline blood pressure. Excluding one trial in an African population with very high baseline blood pressure resulted in smaller overall reductions in blood pressure (SBP mean difference: -3.9, 95% CI: -8.6 to 0.8; DBP mean difference: -1.5, 95% CI: -6.2 to 3.1). Further sensitivity analysis restricted to two high quality trials (n=138) also found non-significant reductions in blood pressure (SBP mean difference: -7.1, 95% CI: -19.9 to 5.7; DBP mean difference: -5.5, 95% CI: -14.5 to 3.5). AUTHORS' CONCLUSIONS: This systematic review found no statistically significant effect of potassium supplementation on blood pressure. Because of the small number of participants in the two high quality trials, the short duration of follow-up, and the unexplained heterogeneity between trials, the evidence about the effect of potassium supplementation on blood pressure is not conclusive. Further high quality RCTs of longer duration are required to clarify whether potassium supplementation can reduce blood pressure and improve health outcomes.

Combined calcium, magnesium and potassium supplementation for the management of primary hypertension in adults.

BACKGROUND: Previous research suggests that increasing dietary intakes of calcium, potassium or magnesium separately may reduce BP to a small degree over the short term. It is unclear whether increasing intakes of a combination of these minerals produces a larger reduction in BP. OBJECTIVES: To evaluate the effects of combined mineral supplementation as a treatment for primary hypertension in adults. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. The search was unrestricted by language or publication status. SELECTION CRITERIA: Inclusion criteria were: 1) RCTs of a parallel or crossover design comparing oral supplements comprising a combination of potassium, and/or calcium, and/or magnesium with placebo, no treatment, or usual care; 2) treatment and follow-up >=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >=85 mmHg with no known primary cause; 4) SBP and DBP reported at end of follow-up. We excluded trials where participants were pregnant, or received antihypertensive medication which changed during the study. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: We included three RCTs (n=277) with between 24 and 28 weeks follow-up. Three combinations of minerals were investigated: potassium & magnesium, calcium & magnesium, and calcium & potassium. One trial investigated combinations of calcium & magnesium and of calcium & potassium, and for each found a statistically non-significant increase in both SBP and DBP. All three trials investigated the combination of potassium & magnesium. None of the trials provided data on mortality or morbidity. The combination of potassium & magnesium compared to control resulted in statistically non-significant reductions in both SBP (mean difference = -4.6 mmHg, 95% CI: -9.9 to 0.7) and DBP (mean difference = -3.8 mmHg, 95% CI: -9.5 to 1.8), although the results were heterogeneous (I(2)=68% and 85% for SBP and DBP respectively).A sensitivity analysis using alternative reported values which accounted for missing data had very little effect on DBP but resulted in a larger, statistically significant reduction in SBP (mean difference = -5.8 mmHg, 95% CI: -10.5 to -1.0). The quality of the trials was not well reported. AUTHORS' CONCLUSIONS: We found no robust evidence that supplements of any combination of potassium, magnesium or calcium reduce mortality, morbidity or BP in adults. More trials are needed to investigate whether the combination of potassium & magnesium is effective.

Magnesium supplementation for the management of essential hypertension in adults.

BACKGROUND: Epidemiological evidence on the effects of magnesium on blood pressure is inconsistent. Metabolic and experimental studies suggest that magnesium may have a role in the regulation of blood pressure. OBJECTIVES: To evaluate the effects of magnesium supplementation as treatment for primary hypertension in adults. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. SELECTION CRITERIA: Inclusion criteria were: 1) RCTs of a parallel or crossover design comparing oral magnesium supplementation with placebo, no treatment, or usual care; 2) treatment and follow-up >/=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg; 4) SBP and DBP reported at end of follow-up. We excluded trials where: participants were pregnant; received antihypertensive medication which changed during the study; or magnesium supplementation was combined with other interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: Twelve RCTs (n=545) with eight to 26 weeks follow-up met our inclusion criteria. The results of the individual trials were heterogeneous. Combining all trials, participants receiving magnesium supplements as compared to control did not significantly reduce SBP (mean difference: -1.3 mmHg, 95% CI: -4.0 to 1.5, I(2)=67%), but did statistically significantly reduce DBP (mean difference: -2.2 mmHg, 95% CI: -3.4 to -0.9, I(2)=47%). Sensitivity analyses excluding poor quality trials yielded similar results. Sub-group analyses and meta-regression indicated that heterogeneity between trials could not be explained by dose of magnesium, baseline blood pressure or the proportion of males among the participants. AUTHORS' CONCLUSIONS: In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of a causal association between magnesium supplementation and blood pressure reduction is weak and is probably due to bias. This is because poor quality studies generally tend to over-estimate the effects of treatment. Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of magnesium supplementation on blood pressure and cardiovascular outcomes.