Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate. RESULTS: In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was -0.66% [six studies; 95% confidence interval (CI) -1.14 to -0.19; I(2) = 88%] with albiglutide, and -1.18% (seven studies; 95% CI -1.34 to -1.02; I(2) = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences -0.40%; 95% CI -0.66 to -0.14; I(2) = 85%, -0.44%; 95% CI -0.58 to -0.29; I(2) = 40% and -0.28; 95% CI -0.45 to -0.10; I(2) = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions. CONCLUSIONS: Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.

Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis.

AIM: To assess the efficacy and safety of the novel sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin compared with placebo or other antidiabetic agents in patients with type 2 diabetes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials. We searched Medline, Embase and the Cochrane Library through December 2013 and grey literature. Two reviewers working independently extracted relevant data and carried out risk-of-bias assessments. We synthesized results using random-effects models and computed weighted mean differences (WMDs) and odds ratios (ORs). RESULTS: We included 10 studies with 6203 participants. Compared with placebo, mean changes in haemoglobin A1c were -0.62% [95% confidence interval (CI) -0.68 to -0.57%] for empagliflozin 10 mg and -0.66% (-0.76 to -0.57%) for empagliflozin 25 mg. Empagliflozin 25 mg daily had glycaemic efficacy similar to metformin or sitagliptin (WMD -0.11%; 95% CI -0.25 to 0.03%), without increasing risk for hypoglycaemia. It was also associated with body weight loss (WMD -1.84; 95% CI -2.30 to -1.38 kg vs. placebo) and had a favourable effect on blood pressure. Incidence of hypoglycaemia with empagliflozin was similar to placebo (OR 1.10; 95% CI 0.87 to 1.39); nevertheless we noted an increased risk for genital tract infections (OR 3.31; 95% CI 1.55 to 7.09). Findings were similar for the 10-mg dosing regimen. CONCLUSIONS: Empagliflozin effectively lowers blood glucose and provides additional clinical benefits including body weight and blood pressure reduction. Ongoing trials will elucidate the long-term safety and effect of empagliflozin on cardiovascular outcomes.

Can UK healthcare workers remotely support medical education in the developing world?: Focus group evaluation.

OBJECTIVES: To evaluate the feasibility of providing regular, live, text-based teaching to medical students and junior doctors in Somaliland using a dedicated case-based medical education website (www.MedicineAfrica.com). DESIGN: Review of MedicineAfrica database for details of teaching sessions held in Somaliland from December 2008-October 2010 and evaluation of user experiences through focus groups. SETTING: King's College Hospital, London, UK and Ahmoud University, Borama, Somaliland. PARTICIPANTS: Final year medical students, newly graduated interns and second year interns at Ahmoud University, Borama, Somaliland. MAIN OUTCOME MEASURES: Qualitative and quantitative user rating of online case-based tutorials in the context of pre-existing educational opportunities available to them. RESULTS: Regular online teaching sessions are received enthusiastically by students and junior doctors and are reported to improve their clinical practice. CONCLUSIONS: Despite technological limitations in Somaliland, a live text-based teaching service can be delivered effectively and streamlined with local curricula. This represents an alternative to traditional static teaching methodologies currently used in international medical education.

A massive binary black-hole system in OJ 287 and a test of general relativity.

Tests of Einstein's general theory of relativity have mostly been carried out in weak gravitational fields where the space-time curvature effects are first-order deviations from Newton's theory. Binary pulsars provide a means of probing the strong gravitational field around a neutron star, but strong-field effects may be best tested in systems containing black holes. Here we report such a test in a close binary system of two candidate black holes in the quasar OJ 287. This quasar shows quasi-periodic optical outbursts at 12-year intervals, with two outburst peaks per interval. The latest outburst occurred in September 2007, within a day of the time predicted by the binary black-hole model and general relativity. The observations confirm the binary nature of the system and also provide evidence for the loss of orbital energy in agreement (within 10 per cent) with the emission of gravitational waves from the system. In the absence of gravitational wave emission the outburst would have happened 20 days later.

Public opinions about mental illness in a Greek area: The influence of socio-demographic factors.

The importance of certain socio-demographic factors, which influence the attitudes and ideas regarding the mentally ill, were investigated in a resident population of a Greek region. An urban and a rural sample of 1,975 inhabitants were selected with an age range between 18 and 65 years. The Greek version of the Opinions about Mental Illness Questionnaire (OMIQ) was used for measuring the attitudes of social discrimination, social restriction, social care, social integration towards the mentally ill and the beliefs for the aetiology of the mental illness. The collected data were statistically analysed with stepwise multiple regression analysis and for the coding of the variables the method of dummy or indicator variables was followed. Educational level, age and place of residence are the main socio-demographic variables on which the OMIQ score depend. The results of this study could lead to the identification of target groups for the organisation of prevention programs aiming at changing public beliefs towards the mentally ill.

The CSF accumulator.

The ability of the central nervous system (CNS) to store and release fluid energy plays an important role in both health and disease. The stored fluid energy is the product of the fluid volume and pressure. How changes in CNS fluid (CSF, blood, or extracellular fluid) energy are distributed is determined by the compliance of the fluid containers and their arrangement. Hydrocephalus and related diseases not only interfere with the absorption of CSF but also interfere with the exchange of CSF in response to positional changes, cardiorespiratory and intraperitoneal energy changes. While shunts allow for the diversion of CSF when the intracranial energy exceeds the absorbing receptacle energy, they do not normalize the return of CSF to the intracranial compartment as needed with the intracranial blood volume or pressure decreases (the accumulator function of the CNS's CSF). A CSF shunt that has an artificial accumulator proximal to the valve can potentially restore the accumulator function towards normal and prevent some of the complications associated with CSF overdrainage.

Cerebrospinal fluid flow through an implanted shunt.

Although the circulation of cerebrospinal fluid enjoys an apparent simplicity, its underlying basis is amazingly complex. Many factors influence how CSF flows through the human central nervous system. In the presence of hydrocephalus and subsequent shunt placement, this system is further complicated. The challenge before us then is to advance our understanding of the mechanisms that underlie CSF circulation, to place within that context the implications of shunt dependency, and to design a shunt system capable of simultaneous redirection of CSF and restoration of the CNS toward normal. Such a new shunt system would have to overcome not only those complications that result from hydrocephalus, but also those that result from the shunt's very placement. The purpose of this publication is 1. to provide an overview of the CSF circulatory system in the context of hydrocephalus and shunt dependency; 2. to explore resultant complications within the framework of those factors that influence CSF circulation within the human biological system as well as those that arise from the factors that influence CSF flow through a shunt; and 3. to propose in brief an alternative shunt valve designed to restore the accumulator function of the CNS toward normal.

Hydrocephalus and the reproductive health of women: the medical implications of maternal shunt dependency in 70 women and 138 pregnancies.

An increasing number of women with cerebrospinal fluid shunts are surviving to child-bearing age, and are making independent decisions in regard to planning their families. As a result, a broad range of interdisciplinary health care professionals will require information about the management of these patients, especially during pregnancy and delivery. The purpose of this ongoing study is to gather comprehensive data from shunted women regarding their clinical history during pregnancy and within the six-month post-partum period. As part of this study, the following questions were addressed: 1. How does maternal shunt dependency influence the course of pregnancy and pregnancy outcomes? 2. What neurosurgical complications characterize this population of patients? 3. What complications of shunt dependency influence obstetrical management including pre-natal testing and delivery? 4. What are the implications of shunt dependency with respect to general reproductive health concerns within this population? A total of 70 respondents, 18-41 years old and accounting for 138 pregnancies, completed a questionnaire providing information on maternal background, medical history, shunt performance during pregnancy, management of delivery, pregnancy outcomes, and unusual complications. One hundred three (103) pregnancies resulted in 105 live births including two surviving sets of twins; of these, 84 occurred in women with ventriculoperitoneal shunts (including both mothers who gave birth to live twins). Four women underwent therapeutic abortions, five delivered pre-term, one mother delivered a stillborn infant, and 16 experienced 32 miscarriages (including two ectopic pregnancies, and 33 fetal losses). Three women had seizures during pregnancy. Nine mothers reported an increase in headache activity during pregnancy. Twelve described abdominal pains during the course of pregnancy with anecdotal reports of increased frequency of painful episodes during the first and third trimesters. Twelve babies were diagnosed with congenital defects, including one pair of fraternal twins individually diagnosed with symmetric parietal foramina. Seven additional children were diagnosed with developmental disabilities including attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), pervasive developmental delay (PDD), and autism. Shunt malfunctions and revisions occurred seven times (four women) during pregnancy, and in 24 pregnancies (13 women) within six months of delivery. One malfunction and revision followed the miscarriage of twins at 12 gestational weeks. No acute malfunctions requiring immediate revision occurred during delivery, although two women reported severe headaches during labor. Transient signs of raised intracranial pressure occurred in 15 mothers over the course of 19 pregnancies which did not require surgical revision of the shunt following delivery or termination of pregnancy. No signs of shunt malfunction were identified in 100 of the pregnancies described in this series; 31 of these resulting in miscarriage and 69 resulting in live births. This study extends observations made previously to a larger population of shunt dependent mothers, and nearly doubles the amount of data available in our last publication. The results suggest that maternal shunt dependency carries a relatively high incidence of complications for some patients, but that proper management of these patients can lead to normal pregnancy and delivery.

Levels of hepatic stimulator substance in liver regenerating process of partially hepatectomized rats pretreated with a single dose of carbon tetrachloride.

Liver regeneration after injury with carbon tetrachloride (CCl4) followed by partial hepatectomy is a complex model involving toxicological, inflammatory, and necrotic processes. In the present study, the time-course of hepatic regenerative process was investigated in relation to hepatic stimulator substance (HSS) activity, administration of a single dose of CCl4 and partial (70%) hepatectomy in male rats. To evaluate liver injury events, the levels of serum aspartic aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured. Hepatic DNA synthesis reached a maximum at 36 hr after hepatectomy in contrast to the reported 24-hr and 32-hr peaks observed in nontreated hepatectomized rats. On the other hand, HSS activity appeared to peak at 28, 40, and 44 hr after hepatectomy in CCl4-treated rats, and it was quite a lot lower at 24, 32, 36, 48, and 60 hr. The hypothesis that HSS promotes liver regeneration but it does not initiate it, as other factors have been found to do, is discussed.

Maternal shunt dependency: implications for obstetric care, neurosurgical management, and pregnancy outcomes and a review of selected literature.

OBJECTIVE: Because more women with cerebrospinal fluid shunts are surviving to child-bearing age, neurosurgeons, obstetricians, and other health care professionals require information about the care of these patients, especially during pregnancy and delivery. The purpose of this study was to gather comprehensive data from women with shunts regarding their clinical histories during and immediately after pregnancy. The following questions were addressed. 1) How does maternal shunt dependency influence the course of pregnancies and pregnancy outcomes? 2) What neurosurgical complications characterize this population of patients? 3) What complications of shunt dependency influence obstetric management, including prenatal testing and delivery? METHODS: A total of 37 respondents (age, 18-41 yr), accounting for 77 pregnancies, completed a questionnaire providing information on maternal background and medical history, shunt performance during pregnancy, management of delivery, pregnancy outcomes, and unusual complications. RESULTS: Fifty-six pregnancies resulted in live births; of these, 47 occurred in women with ventriculoperitoneal shunts. Three women underwent therapeutic abortions, 1 experienced preterm delivery, and 8 experienced 17 miscarriages. Four women experienced seizures during pregnancy, five reported third-trimester headaches, and eight described abdominal pains during the first and third trimesters. Four babies were diagnosed as having congenital defects. Shunt malfunctions and revisions occurred 10 times in 7 women, either during pregnancy or within 6 months after delivery. No acute malfunctions occurred during delivery. Forty-seven cases, representing 84% of all pregnancies, exhibited no shunt malfunctions or revisions. CONCLUSION: This study extends previous observations to a larger population of shunt-dependent mothers. The results suggest that maternal shunt dependency entails a relatively high incidence of complications but that proper care of these patients can lead to normal pregnancies and deliveries.

Pain intensity in nondiabetic patients with myocardial infarction or unstable angina. Its association with clinical and psychological features.

Sixty nondiabetic coronary artery disease (CAD) patients submitted to coronary angiography were asked to rate (score 0 to 20) pain intensity (RPI) during their last major anginal episode having occurred prior to coronary angiography. This parameter was examined in relation to other variables of CAD and to psychological features. Stepwise regression analysis revealed that RPI was not related to New York Heart Association (NYHA) classification of angina or to angiographic variables. Yet, RPI was found to be significantly affected by psychological features: higher RPI scores were reported by low state anxiety patients (P=0.008), by Type A coronary-prone behavior patients (P=0.02) and by patients with high depression (P=0.03).

The CSF accumulator: its role in the central nervous system and implications for advancing hydrocephalus shunt technology.

The 'cerebrospinal fluid (CSF) accumulator' plays an important physiological role in the healthy central nervous system as both a shock absorber and regulator of drainage. In the presence of hydrocephalus, this function is compromised by resistance to the flow of CSF. It is further compromised by the placement of a standard shunt which allows only for one-way directional diversion of the fluid. Complications associated with shunt dependency may be a direct consequence of both the condition, and a failure of existing systems to restore the normal accumulator function. This article reviews the pathophysiology of the 'CSF accumulator' as it relates to hydrocephalus and its management, and proposes a biomimetic shunt designed to restore the 'CSF accumulator' toward normal. It is hoped that such a device will support normalization of intracranial pressure and restore an appropriate level of CSF volume in the shunted patient.

Psychiatric morbidity among repatriated Greek migrants in a rural area.

This paper reports on psychiatric case identification by the application of the Structured Clinical Interview for DSM-III-R (SCID) in a sample of 198 Greek migrants repatriated from western europe in a northwestern province of Greece. The current (1 month) prevalence of psychiatric morbidity, based on the total number of diagnosed cases, was found to be 43.4%. Lifetime prevalence of psychiatric disorders was found to be higher (49.4%). The majority of the sample were diagnosed as suffering from anxiety disorders and dysthymia. Psychiatric disorders were found to be more prevalent among middle-aged respondents. Duration of stay in the foreign country was a factor correlated with psychiatric morbidity. Of short-term migrants 54% were found to suffer from specific nosological entities, whereas 32% of long-term migrants were diagnosed as cases. The results are discussed within the framework of the existing sociocultural context of emigration and repatriation.

Alcohol and drug use, family situation and school performance in adolescent children of alcoholics.

A survey was conducted in a population of about 8000 Greek high school students (grades 9 and 12) in order to investigate factors possibly contributing to alcohol consumption. A self-rating multiple choice questionnaire was used. The present report focuses on students with alcoholic parents. Parameters studied include students' alcohol and drug use, school performance, family relationships, socioeconomic factors and parental control. In 3.3% of the sample parental alcoholism was reported. The results indicated that parental alcoholism is a strong predictor variable for the student's alcohol and drug use. Furthermore, predictability of the student's alcohol and drug use is increased when relatives' and friends' alcoholism are taken into account. Thus, family and/or peer actual alcohol use patterns appear to be a strong influence on adolescent alcohol and drug use. School performance is worse in children of alcoholics, and family situations (eg. divorces) as well as family dynamics (relationships with the family) are disturbed, in comparison with families of students with nonalcoholic parents. These results are discussed in terms of 'modelling' for drinking and drug behaviour and the socialisation process within the family.

Factors related to the presence of autoantibodies in patients with chronic mental disorders.

Serum samples from 307 patients with various chronic mental disorders were examined for the presence of several autoantibodies. Autoantibodies detected included antinuclear antibodies (ANA) in 122/307 (39.7%), rheumatoid factor (RF) in 23/307 (7.5%), anticardiolipin antibodies (anti-CL) in 23/304 (7.6%, IgM in 12 patients, IgG in 13 patients). Isolated cases with IgG anti-dsDNA, anti-Ro(SSA), and anti-Ro(SSA)/anti-La(SSB) were also identified. The analysis of data revealed that the aging process in patients studied contributed significantly to the incidence of ANA (p less than 0.0001) and RF (p less than 0.01). In addition, the chronic administration of chlorpromazine (CPZ) was associated with the presence of ANA (p less than 0.03) as well as with the presence of IgM and/or IgG anti-CL antibodies (p less than 0.003). Finally, the diagnosis of schizophrenia correlated with the presence of ANA (p less than 0.001). This study represents the autoantibody profile of patients with chronic mental disorders and emphasizes the multifactorial origin of autoantibody response in psychiatric patients.

Personality structure disturbances and psychiatric manifestations in primary Sjögren's syndrome.

It has been recently suggested that primary Sjögren's syndrome (SS) patients present with a variety of personality structure disturbances and psychiatric symptoms. To evaluate this finding further, we assessed hostility structure and psychiatric symptoms in 33 Sjögren's syndrome patients and compared the results with those of 33 healthy women, and 41 women with solid malignant tumors. The utilized psychometric instruments were the hostility and direction of hostility questionnaire (HDHQ) and the symptom checklist 90R (SCL-90R). High levels of introverted hostility were reported by SS patients in relation to the other two groups. Cancer and SS patients reported higher scores on anxiety and depressive symptoms compared to the healthy women, but the differences were not significant. In addition, high scores on paranoid ideation, somatization and obsessive compulsive symptoms were found in SS patients compared to the cancer and healthy controls. The results strongly suggest that psychiatric disorders are common in primary SS patients, who may need appropriate therapy.

An investigation into the relationship between hostility and criminality in schizophrenia.

The possible relationship between hostility and criminality was investigated in a sample of 134 schizophrenic patients at the public psychiatric hospital in Athens. The sample consisted of two groups of patients (n = 67 each); an offenders groups and a non-offenders group. No significant differences in hostility were found between the groups. Moreover, degree of hostility bore no relationship to severity of criminal offence.