Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations

The MIF antagonist ISO-1 attenuates corticosteroid-insensitive inflammation and airways hyperresponsiveness in an ozone-induced model of COPD

Copyright © 2016 Russell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however. Methods. Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from nonsmokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays. Results. MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR. Conclusion MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

Increased circulating ANG II and TNF-α represents important risk factors in obese Saudi adults with hypertension irrespective of diabetic status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk

Molecular, morphological and acoustic identification of Eumops maurus and Eumops hansae (Chiroptera: Molossidae) with new reports from Central Amazonia

Eumops maurus and Eumops hansae are rarely captured Neotropical molossid bats for which information on taxonomy, natural history, and spatial distribution are scarce. This translates into a poor understanding of their ecology and limits the delimitation of useful characters for their identification. Here, we describe records of these two molossids from the Central Brazilian Amazon, providing data on their external and craniodental morphology, DNA barcode (COI) sequences complemented by acoustic data for the species. Morphological characters, DNA sequence data and phylogenetic relationships within the genus Eumops were consistent with those previously described for both species. Echolocation call characteristics did not differ significantly so as to be useful for separating E. maurus and E. hansae from other congeners. Our records are, respectively the first and the second for Central Amazonia as one individual previously attributed to Eumops amazonicus from Manaus may be considered a junior synonym for E. hansae. These new records increase the extent of the species’ known ranges, partially filling in previous existing gaps in their distribution in central South America. Our data further suggest that these molossid bats forage in a wider range of habitats than previously thought

A mathematical model of the human metabolic system and metabolic flexibility

In healthy subjects some tissues in the human body display metabolic flexibility, by this we mean the ability for the tissue to switch its fuel source between predominantly carbohydrates in the post prandial state and predominantly fats in the fasted state. Many of the pathways involved with human metabolism are controlled by insulin, and insulin- resistant states such as obesity and type-2 diabetes are characterised by a loss or impairment of metabolic flexibility. In this paper we derive a system of 12 first-order coupled differential equations that describe the transport between and storage in different tissues of the human body. We find steady state solutions to these equations and use these results to nondimensionalise the model. We then solve the model numerically to simulate a healthy balanced meal and a high fat meal and we discuss and compare these results. Our numerical results show good agreement with experimental data where we have data available to us and the results show behaviour that agrees with intuition where we currently have no data with which to compare

Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

© The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio

The Heartbleed bug : insecurity repackaged, rebranded and resold

The emergence of a post-industrial information economy shaped by and around networked communication technology has presented new opportunities for identity theft. In particular, the accidental leakage or deliberate harvesting of information, via either hacking or social engineering, is an omnipresent threat to a large number of commercial organisations and state agencies who manage digital databases and sociotechnical forms of data. Throughout the twenty-first century the global media have reported on a series of data breaches fuelling amongst the public an anxiety concerning the safety and security of their personal and financial data. With concern outpacing reliable information a reassurance gap has emerged between the public's expectations and the state's ability to provide safety and security online. This disparity presents a significant opportunity for a commercial computer crime control industry who has sought to position itself as being able to offer consumer citizens the antidotes for such ills. This paper considers how neoliberal discourses of cybercrime control are packaged, branded and sold, through an examination of the social construction of the Heartbleed bug. It demonstrates how security company Codenomicon masterfully communicated the vulnerability, the product of a simple coding error, through its name, a logo and an accompanying website, in turn, shaping news coverage across the mainstream media and beyond

New Foundations: Pseudo-pacification and special liberty as potential cornerstones of a multi-level theory of homicide and serial murder

Over the past 30 years the industrialized West has witnessed a move towards space, heterogeneity and subjectivity in the criminological study of violence and homicide. Although large-scale quantitative studies of the temporal and spatial distribution of homicide continue to provide a broad empirical context, aetiological explanations tend to be based on analyses of the heterogeneous psychological interactions and experiences of individual subjects at the micro-level. However, mid-range studies of the temporal and spatial distribution of perpetrators and victims of homicide between unrelated adults have provided a useful link between the micro- and macro-levels. Focusing primarily on British homicide and serial murder, this article attempts to strengthen this link by combining contemporary micro-analyses of the subjective motives of perpetrators with mid-range analyses of space, which can therefore be seen as part of the structural tradition of theorizing about homicide and serial murder. Placing these analyses in a broad underlying context constituted by major historical shifts in political economy and the cultural forms of ‘pseudo-pacification’ and ‘special liberty’ will lay the initial cornerstones for an integrated multi-level theory. © The Author(s) 2014

Obesity and poor breast cancer prognosis: an illusion because of hormone replacement therapy?

High body mass index (BMI) and use of hormone replacement therapy (HRT) increase the risk of postmenopausal breast cancer. It has been shown that BMI modifies the effect of HRT, as its influence is most pronounced in lean women. We investigated the influence of BMI and HRT on prognosis in 2640 postmenopausal women diagnosed with breast cancer in Sweden in 1993–1995, taking into account HRT and mammography before diagnosis. Logistic and Cox regression were used. In non-users of HRT, obese women (BMI >30) compared with normal weight women (BMI <25) had a similar prognosis (hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.8–1.6), despite larger tumours found in obese women. Obese HRT users had less favourable tumour characteristics and poorer prognosis compared with normal weight women (HR 3.7, 95% CI 1.9–7.2). The influence of BMI on breast cancer prognosis was similar whether diagnosed by mammographic screening or not. We found a similar prognosis of postmenopausal breast cancer-specific death regardless of BMI in non-users of HRT, but among HRT users obesity was associated with a poorer breast cancer prognosis