Forest plot showing random effects model of overall mortality due to severe malaria according to region.

<p>Forest plot showing random effects model of overall mortality due to severe malaria according to region.</p

Clinical Features and Outcome in Children with Severe <i>Plasmodium falciparum</i> Malaria: A Meta-Analysis

<div><p>Background</p><p>Although global malaria mortality is declining, estimates may not reflect better inpatient management of severe malaria (SM) where reported case fatality rates (CFRs) vary from 1–25%.</p><p>Methods</p><p>A meta-analysis of prospective studies of SM was conducted to examine i) whether hypothesized differences between clinical features and outcome in Melanesian compared with African or Asian children really exist, and ii) to explore temporal changes in overall and complication-specific CFRs. The proportions of different SM complications and, overall and complication-specific CFRs were incorporated into the meta-analysis. Adjustments were made for study-level covariates including geographic region, SM definition, artemisinin treatment, median age of participants and time period.</p><p>Findings</p><p>Sixty-five studies were included. Substantial heterogeneity (<i>I</i>²>80%) was demonstrated for most outcomes. SM definition contributed to between-study heterogeneity in proportions of cerebral malaria (CM), metabolic acidosis (MA), severe anemia and overall CFR, whilst geographic region was a significant moderator in for CM and hypoglycemia (HG) rates. Compared with their African counterparts, Melanesian children had lower rates of HG (10% [CI95 7–13%] versus 1% [0–3%], <i>P</i><0.05), lower overall CFR (2% [0–4%] versus 7% [6–9%], <i>P</i><0.05) and lower CM-specific CFR (8% [0–17%] versus 19% [16–21%], <i>P</i><0.05). There was no temporal trend for overall CFR and CM-specific CFR but declining HG- and MA- specific CFRs were observed.</p><p>Interpretation</p><p>These data highlight that recent estimates of declining global malaria mortality are not replicated by improved outcomes for children hospitalized with SM. Significant geographic differences in the complication rates and subsequent CFRs exist and provide the first robust confirmation of lower CFRs in Melanesian children, perhaps due to less frequent HG.</p></div

Flow diagram showing studies included in meta-analysis.

<p>Flow diagram showing studies included in meta-analysis.</p

Heterogeneity and the effect of moderators on heterogeneity for overall and clinical feature-specific case fatality rates in descriptive studies of severe <i>Plasmodium falciparum</i> malaria.

<p>NS, No statistically significant contribution to overall heterogeneity; Def, Definition; *, ** and ***, <i>P</i>-values<0.05, <0.01 and <0.0001, respectively.</p>a<p>Includes 7 studies where overall case fatality rates are calculated according to treatment regimen.</p>b<p>Includes 9 studies where case fatality rates due to deep coma are calculated separately according to treatment regimen.</p>c<p>Children with overlapping syndrome comprising coma, severe anemia and any of: metabolic acidosis, respiratory distress or hyperlactatemia.</p

Heterogeneity and the effect of moderators for proportions and case fatality rates according to Blantyre Coma Score in deeply comatose children from descriptive studies of severe <i>Plasmodium falciparum</i> malaria.

<p>BCS, Blantyre Coma Score; CFR, Case Fatality Rate; NS, No statistically significant contribution to overall heterogeneity; * and **, <i>P</i>-values<0.05 and <0.01, respectively.</p

The Relationship between Hypomagnesemia, Metformin Therapy and Cardiovascular Disease Complicating Type 2 Diabetes: The Fremantle Diabetes Study

<div><p>Background</p><p>Low serum magnesium concentrations have been associated with cardiovascular disease risk and outcomes in some general population studies but there are no equivalent studies in diabetes. Metformin may have cardiovascular benefits beyond blood glucose lowering in type 2 diabetes but its association with hypomagnesemia appears paradoxical. The aim of this study was to examine relationships between metformin therapy, magnesium homoeostasis and cardiovascular disease in well-characterized type 2 patients from the community.</p><p>Methods and Findings</p><p>We studied 940 non-insulin-treated patients (mean±SD age 63.4±11.6 years, 49.0% males) from the longitudinal observational Fremantle Diabetes Study Phase I (FDS1) who were followed for 12.3±5.3 years. Baseline serum magnesium was measured using stored sera. Multivariate methods were used to determine associates of prevalent and incident coronary heart disease (CHD) and cerebrovascular disease (CVD) as ascertained from self-report and linked morbidity/mortality databases. 19% of patients were hypomagnesemic (serum magnesium <0.70 mmol/L). Patients on metformin, alone or combined with a sulfonylurea, had lower serum magnesium concentrations than those on diet alone (<i>P</i><0.05). There were no independent associations between serum magnesium or metformin therapy and either CHD or CVD at baseline. Incident CVD, but not CHD, was independently and inversely associated with serum magnesium (hazard ratio (95% CI) 0.28 (0.11–0.74); <i>P = </i>0.010), but metformin therapy was not a significant variable in these models.</p><p>Conclusions</p><p>Since hypomagnesemia appears to be an independent risk factor for CVD complicating type 2 diabetes, the value of replacement therapy should be investigated further, especially in patients at high CVD risk.</p></div

Independent associates of serum magnesium at baseline in the most parsimonious model (adjusted R² = 0.136), with entry of blood glucose-lowering treatment group after adjustment for these variables.

<p>Independent associates of serum magnesium at baseline in the most parsimonious model (adjusted R² = 0.136), with entry of blood glucose-lowering treatment group after adjustment for these variables.</p

Baseline characteristics of patients by blood glucose-lowering therapy including variables relevant to magnesium homoeostasis.

<p>Data are percentages, mean ± SD, geometric mean (SD range) or median [inter-quartile range].</p>a<p><i>P</i><0.05 vs diet alone; ^b<i>P</i><0.05 vs metformin alone; ^c<i>P</i><0.05 vs sulfonylurea alone, unadjusted for multiple comparisons.</p><div><p>Data are percentages, mean±SD, geometric mean (SD range) or median [inter-quartile range].</p> <p>^a<0.05 vs diet alone; ^b<0.05 vs metformin alone; ^c<0.05 vs sulfonylurea alone, unadjusted for multiple comparisons.</p></div

Baseline characteristics of type 2 patients by serum magnesium category.

<p>Data are percentages, mean±SD, geometric mean (SD range) or median [inter-quartile range].</p><p>Data are percentages, mean±SD, geometric mean (SD range) or median [inter-quartile range].</p

The utility of the Diabetes Anxiety Depression Scale in Type 2 diabetes mellitus: The Fremantle Diabetes Study Phase II

<div><p>Background</p><p>Previous research using latent class analysis (LCA) identified classes of people with type 2 diabetes and specific profiles of depression and anxiety. Since LCA-derived anxious depression strongly predicts cardiovascular outcomes and mortality but cannot be applied to individuals, we developed a validated combined depression-anxiety metric, the Diabetes Anxiety Depression Scale (DADS), for potential clinical application in people with type 2 diabetes.</p><p>Methods</p><p>1,337 participants with type 2 diabetes from the observational community-based Fremantle Diabetes Study Phase II completed the Patient Health Questionnaire 9-item version (PHQ-9) to assess symptoms of depression, and the Generalised Anxiety Disorder Scale (GADS) to assess symptoms of anxiety. A single score was calculated by adding all the PHQ-9 items and the four GADS items used for the LCA. Cut-off scores were calculated with Receiver Operating Characteristic (ROC) area under the curve (AUC).</p><p>Results</p><p>The optimum cut-off scores in terms of sensitivity, specificity, positive and negative predictive value were 18 points for major anxious depression and 8 points for minor anxious depression. A score of 8–17 was associated with a significantly increased incidence of coronary heart disease, whereas a score 18–39 was associated with an increase in both coronary heart disease and cardiovascular mortality.</p><p>Conclusions</p><p>The DADS has strong psychometric validity in the identification of mixed depression-anxiety in type 2 diabetes, and may contribute to cardiovascular risk prediction.</p></div