tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.

/pdf/kdigo-clinical-practice-guidelines-for-acute-kidney-injury-27tybolw7l.pdf

KDIGO clinical practice guidelines for acute kidney injury.

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Modern Applied Statistics With S

Erik Eriksen is a remarkable individual. He has no college degrees yet is Professor of Human Development at Harvard University. He came to psychology via art, which explains why the reader will find him painting contexts and backgrounds rather than stating dull facts and concepts. He has been a training psychoanalyst for many years as well as a perceptive observer of cultural and social settings and their effect on growing up. This is not just a book on childhood. It is a panorama of our society. Anxiety in young children, apathy in American Indians, confusion in veterans of war, and arrogance in young Nazis are scrutinized under the psychoanalytic magnifying glass. The material is well written and devoid of technical jargon. The theme of the volume is that it is human to have a long childhood which will leave a lifelong residue of emotional immaturity in man. Primitive groups and

Childhood and Society.

Funnel plots, and tests for funnel plot asymmetry, have been widely used to examine bias in the results of meta-analyses. Funnel plot asymmetry should not be equated with publication bias, because it has a number of other possible causes. This article describes how to interpret funnel plot asymmetry, recommends appropriate tests, and explains the implications for choice of meta-analysis model

https://www.bmj.com/content/bmj/343/bmj.d4002.full.pdf

Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials

2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular riskThe Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)

Objectives To assess the evidence for the clinical effectiveness of ultrasound guided central venous cannulation. Data sources 15 electronic bibliographic databases, covering biomedical, science, social science, health economics, and grey literature. Design Systematic review and meta-analysis of randomised controlled trials. Populations Patients scheduled for central venous access. Intervention reviewed Guidance using real time two dimensional ultrasonography or Doppler needles and probes compared with the anatomical landmark method of cannulation. Data extraction Risk of failed catheter placement (primary outcome), risk of complications from placement, risk of failure on first attempt at placement, number of attempts to successful catheterisation, and time (seconds) to successful catheterisation. Data synthesis 18 trials (1646 participants) were identified. Compared with the landmark method, real time two dimensional ultrasound guidance for cannulating the internal jugular vein in adults was associated with a significantly lower failure rate both overall (relative risk 0.14, 95% confidence interval 0.06 to 0.33) and on the first attempt (0.59, 0.39 to 0.88). Limited evidence favoured two dimensional ultrasound guidance for subclavian vein and femoral vein procedures in adults (0.14, 0.04 to 0.57 and 0.29, 0.07 to 1.21, respectively). Three studies in infants confirmed a higher success rate with two dimensional ultrasonography for internal jugular procedures (0.15, 0.03 to 0.64). Doppler guided cannulation of the internal jugular vein in adults was more successful than the landmark method (0.39, 0.17 to 0.92), but the landmark method was more successful for subclavian vein procedures (1.48, 1.03 to 2.14). No significant difference was found between these techniques for cannulation of the internal jugular vein in infants. An indirect comparison of relative risks suggested that two dimensional ultrasonography would be more successful than Doppler guidance for subclavian vein procedures in adults (0.09, 0.02 to 0.38). Conclusions Evidence supports the use of two dimensional ultrasonography for central venous cannulation.

https://www.bmj.com/content/bmj/327/7411/361.full.pdf

Ultrasonic locating devices for central venous cannulation: meta-analysis.

This paper emphasizes the importance of distinguishing between the prevalence, incidence and cumulative incidence of inhibitors in haemophilia A. Incidence and cumulative incidence data will include patients with transient inhibitors or whose inhibitors have been eliminated by treatment. As these will not be included in prevalence data, prevalence studies will tend to give rise to lower figures than incidence studies. As a result, the most accurate estimates of the true risk of inhibitor development comes from prospective studies of newly diagnosed haemophiliacs who are tested regularly for the presence of inhibitors. This paper reports a systematic review of the best available evidence relating to the epidemiology of inhibitors in haemophilia A. Cohort studies, registry data reporting incidence or prevalence of inhibitors in patients with haemophilia A, and prospective studies of factor VIII (FVIII) in the treatment of previously untreated patients which reported the development of inhibitors as an outcome, were included in the review. The overall prevalence of inhibitors in unselected haemophiliac populations was found to be 5-7%. The cumulative risk of inhibitor development varied (0-39%). Incidence and prevalence were substantially higher in patients with severe haemophilia. Studies of patients using a single plasma-derived FVIII (pdFVIII) preparation reported lower inhibitor incidence than those using multiple pdFVIII preparations or single recombinant FVIII preparations. Incidence data should be used to estimate the likely demand for treatments aimed at eliminating inhibitors, whereas the best estimates of the overall burden to the National Health Service (NHS) of treating bleeding episodes in patients with continuing inhibitors will come from prevalence studies.

The epidemiology of inhibitors in haemophilia A: a systematic review.

BACKGROUND: Generic preference-based measures of health like the EQ-5D and SF-6D(®) are increasingly being used in economic evaluation and outcome assessment. However, there are concerns as to whether or not these generic measures are appropriate for use in people with mental health problems. OBJECTIVES: The EQ-5D and SF-36(®) (including its derivatives the SF-12(®) and SF-6D) were assessed using the psychometric criteria of validity and responsiveness using quantitative and qualitative methods. Another aim was to estimate mapping functions between the EQ-5D and SF-6D and condition-specific measures, where appropriate. DESIGN: Four studies were undertaken to examine the appropriateness of the measures: (1) a systematic review of quantitative evidence on validity and responsiveness; (2) a further quantitative assessment of these criteria using existing data sets; (3) a review of qualitative research on the quality of life of people with mental health problems; and (4) qualitative semistructured interviews of people with a full range of problems. A fifth study estimated mapping functions between mental health-specific measures and the EQ-5D and SF-6D. SETTING: A choice of venue was offered for the interviews including the participant's own home, a room at the university or a centre frequently used by mental health services. PARTICIPANTS: The interviews were undertaken with 19 people with a broad range of mental health problems at varying levels of severity. MAIN OUTCOME MEASURES: The reviews included the EQ-5D and SF-36 (and the SF-12 and SF-6D). The psychometric analysis included the Hospital Anxiety and Depression Scale (HADS), Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM), Generalised Anxiety Disorder Assessment (GAD-7), General Health Questionnaire (GHQ-12) and Patient Health Questionnaire (PHQ-9). RESULTS: (1) and (2) The EQ-5D and SF-36 achieved an adequate level of performance in depression, and to some extent in anxiety and personality disorder. Results from the psychometric analyses in schizophrenia and bipolar disorder have been more mixed. (3) A framework analysis of 13 studies identified six major themes. (4) The interview data fitted the themes from the review well and resulted in minor modifications to the themes. The final set of themes comprised: well-being and ill-being; control, autonomy and choice; self-perception; belonging; activity; hope and hopelessness; and physical health. CONCLUSIONS: The EQ-5D and SF-36 achieved mixed results in the quantitative testing against psychometric criteria. The qualitative analysis suggests this is because they provide a very limited coverage of themes identified by people with mental health problems. Recommendations for future work include the development of new preference-based measures in mental health that are based on, or substantially revise, an existing measure.

/pdf/a-systematic-review-psychometric-analysis-and-qualitative-3e1vwax17d.pdf

A systematic review, psychometric analysis and qualitative assessment of generic preference-based measures of health in mental health populations and the estimation of mapping functions from widely used specific measures.

To identify the domains of quality of life important to people with mental health problems. A systematic review of qualitative research undertaken with people with mental health problems using a framework synthesis. We identified six domains: well-being and ill-being; control, autonomy and choice; self-perception; belonging; activity; and hope and hopelessness. Firstly, symptoms or ‘ill-being’ were an intrinsic aspect of quality of life for people with severe mental health problems. Additionally, a good quality of life was characterised by the feeling of being in control (particularly of distressing symptoms), autonomy and choice; a positive self-image; a sense of belonging; engagement in meaningful and enjoyable activities; and feelings of hope and optimism. Conversely, a poor quality life, often experienced by those with severe mental health difficulties, was characterized by feelings of distress; lack of control, choice and autonomy; low self-esteem and confidence; a sense of not being part of society; diminished activity; and a sense of hopelessness and demoralization. Generic measures fail to address the complexity of quality of life measurement and the broad range of domains important to people with mental health problems.

/pdf/quality-of-life-of-people-with-mental-health-problems-a-b5cqmjio4e.pdf

Quality of life of people with mental health problems: a synthesis of qualitative research

.
Objectives. To study the evidence on the efficacy and safety of ezetimibe monotherapy for the treatment of primary (heterozygous familial and non-familial) hypercholesterolaemia.

Design.  Systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods.  Eleven electronic bibliographic databases covering the biomedical, scientific and grey literature were searched from inception and supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of RCTs, with a minimum treatment duration of 12 weeks, which compared ezetimibe monotherapy (10 mg per day) with placebo.

Results.  In the absence of data from clinical outcome trials, surrogate endpoints such as changes in lipid concentrations were used as indicators of clinical outcomes. A meta-analysis of eight randomized, double-blind, placebo-controlled trials (all 12 weeks) showed that ezetimibe monotherapy was associated with a statistically significant mean reduction in LDL cholesterol (from baseline to endpoint) of −18.58%, (95% CI: −19.67 to −17.48, P < 0.00001) compared with placebo. Significant (P < 0.00001) changes were also found in total cholesterol (−13.46%, 95% CI: −14.22 to −12.70), HDL cholesterol (3.00%, 95% CI: 2.06–3.94) and triglyceride levels (−8.06%, 95% CI: −10.92 to −5.20). Ezetimibe monotherapy appeared to be well tolerated with a safety profile similar to placebo.

Conclusions.  In a meta-analysis restricted to short-term trials in hypercholesterolaemia, significant potentially favourable changes in lipid and lipoprotein levels relative to baseline occurred with ezetimibe monotherapy. Further long-term studies with cardiovascular and other clinical outcome data are needed to assess the efficacy and safety of ezetimibe more fully.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2008.02062.x

Suzy Paisley

Papers

Ultrasonic locating devices for central venous cannulation: meta-analysis.

The epidemiology of inhibitors in haemophilia A: a systematic review.

A systematic review, psychometric analysis and qualitative assessment of generic preference-based measures of health in mental health populations and the estimation of mapping functions from widely used specific measures.

Quality of life of people with mental health problems: a synthesis of qualitative research

Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials.