background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

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Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

2D\n: two-dimensional\n99mTc-DPD\n: 99mTechnetium-3,3-diphosphono- 1,2-propanodi-carboxylic acid\nACE\n: angiotensin-converting enzyme\nAF\n: atrial fibrillation\nAL\n: amyloid light chain\nAR\n: aortic regurgitation\nARB\n: angiotensin receptor blocker\nATTR\n: amyloidosis-transthyretin type\nAV\n: atrioventricular\nBiVAD\n: biventricular assist device\nBNP\n: brain natriuretic peptide\nBPM\n: Beats per minute\nCCS\n: Canadian Cardiovascular Society\nCFC\n: cardiofacialcutaneous\nCHA2DS2-VASc\n: Congestive Heart failure, hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65–74, and Sex (female)\nCMR\n: cardiac magnetic resonance\nCRT\n: cardiac resynchronization therapy\nCRT-D\n: cardiac resynchronization therapy-defibrillator\nCRT-P\n: Cardiac resynchronization therapy with a pacemaker\nCT\n: computed tomography\nDC\n: direct current\nDNA\n: deoxyribonucleic acid\nE/A\n: ratio of mitral peak velocity of early filling (E) to mitral peak velocity of late filling (A)\nE/e’\n: ratio of early transmitral flow velocity (E) to early mitral annulus velocity (e’)\nEACTS\n: European Association for Cardio-Thoracic Surgery\nECG\n: electrocardiogram\nEF\n: ejection fraction\nEPS\n: electrophysiological study\nESC\n: European Society of Cardiology\nFDA\n: (US) Food and Drug Administration\nFHL1\n: four and a half LIM domains 1\nHAS-BLED\n: hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly (>65 years), drugs/alcohol concomitantly\nHCM\n: hypertrophic cardiomyopathy\nhs-cTnT\n: high sensitivity cardiac troponin T\nHTS\n: high throughput sequencing\nICD\n: implantable cardioverter defibrillator\nILR\n: implantable loop recorder\nINR\n: international normalized ratio\nIUD\n: intrauterine device\nLA\n: left atrium\nLAMP-2\n: lysosome-associated membrane protein 2\nLBBB\n: left bundle branch block\nLEOPARD\n: Lentigines, ECG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, and sensory-neural Deafness\nLGE\n: late gadolinium enhancement\nLV\n: left ventricular\nLVAD\n: left ventricular assist device\nLVH\n: left ventricular hypertrophy\nLVOTO\n: left ventricular outlow tract obstruction\nMADIT-RIT\n: Multicenter Automatic Defibrillator Implantation Trial—Reduce Inappropriate Therapy\nMAPK\n: mitogen activated protein kinase\nMELAS\n: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes\nMERFF\n: myoclonic epilepsy with ragged red fibres\nMRA\n: mineralocorticoid receptor antagonist\nMYBPC3\n: myosin-binding protein C, cardiac-type\nMYH7\n: myosin-7 (s-myosin heavy chain)\nMYL3\n: myosin light chain 3\nNOAC\n: new oral anticoagulants\nNSVT\n: non-sustained ventricular tachycardia\nNT-proBNP\n: N-terminal pro brain natriuretic peptide\nNYHA\n: New York Heart Association\nOAC\n: oral anticoagulants\no.d.\n: omni die (every day)\nPC-CMR\n: phase contrast cardiac magnetic resonance\nPDE5\n: phosphodiesterase type 5\nPET\n: positron emission tomography\nPRKAG2\n: gamma-2 sub-unit of the adenosine monophosphate-activated protein kinase\nRAAS\n: renin angiotensin aldosterone system\nRV\n: right ventricular\nSAM\n: systolic anterior motion\nSCD\n: sudden cardiac death\nSAA\n: septal alcohol ablation\nS-ICD™\n: Subcutaneous lead implantable cardioverter defibrillator\nSPECT\n: single photon emission computed tomography\nSSFP\n: steady-state free precession\nSVT\n: supraventricular tachycardia\nTOE\n: transoesophageal echocardiography\nTNNI3\n: troponin I, cardiac muscle\nTNNT2\n: troponin T, cardiac muscle\nTPM1\n: tropomyosin alpha-1 chain\nTTE\n: transthoracic echocardiography\nTTR\n: transthyretin\nVF\n: ventricular fibrillation\nVKA\n: vitamin K antagonist\nVT\n: ventricular tachycardia\nWHO\n: World Health Organization\n\nGuidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting health professionals in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk-benefit-ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help the health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.\n\nA great number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organisations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated.\n\nMembers of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for management (including diagnosis, treatment, prevention and rehabilitation) of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk-benefit-ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular management options were weighed and graded according to predefined scales, as outlined in Tables 1 and 2 .\n\nThe experts of …

2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC)

We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low-income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the world's population suggests a critical need for further research and capacity building in low- and middle-income countries. Autism Res 2012, 5: 160–179. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

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Global Prevalence of Autism and Other Pervasive Developmental Disorders

This article summarizes evidence and issues associated with psychological assessment. Data from more than 125 meta-analyses on test validity and 800 samples examining multimethod assessment suggest 4 general conclusions: (a) Psychological test validity is strong and compelling, (b) psychological test validity is comparable to medical test validity, (c) distinct assessment methods provide unique sources of information, and (d) clinicians who rely exclusively on interviews are prone to incomplete understandings. Following principles for optimal nomothetic research, the authors suggest that a multimethod assessment battery provides a structured means for skilled clinicians to maximize the validity of individualized assessments. Future investigations should move beyond an examination of test scales to focus more on the role of psychologists who use tests as helpful tools to furnish patients and referral sources with professional consultation.

Psychological Testing and Psychological Assessment: A Review of Evidence and Issues.

on to develop full blown Parkinson's disease with rigidity and bradykinesia in the next few years. For those interested in the mechanisms of tremor, there are the customary authoritative reviews by Llinas, De Long, Lamarre, Rothwell and Deuschl, but uncertainty remains with respect to the relative importance of central autonomous generators and instability of peripheral reflex loops. Well written chapters are also included on primary orthostatic tremor and its relationship to essential tremor, writing tremor, neuropathic tremor, midbrain tremor and the increasingly acknowledged psychogenic tremors. Complex interrelationship between dystonia and postural tremor is also covered in depth. This cornucopia will be coveted and dipped into by those neurologists with a special interest in abnormal movement disorders, but who would not consider themselves to have a research interest in tremor. However, for the majority of clinicians involved in the hurly burly of clinical practice, I suspect that regrettably time and cost factors will conspire together to keep this excellent book out of reach. ANDREW LEES

https://jnnp.bmj.com/content/jnnp/59/3/346.1.full.pdf

Contributions to Neuropsychological Assessment

OBJECTIVE: The purpose of this study was to evaluate all available trial-based evidence on the effectiveness of clozapine in schizophrenia as compared with conventional neuroleptics. METHOD: All randomized, controlled trials comparing clozapine with a conventional neuroleptic in which there was satisfactory concealment of patients’ treatment allocation were located through electronic searches in all languages of several databases and through contacting authors of recent trials as well as the manufacturer of clozapine. At least two independent reviewers assessed trials for inclusion in the study and extracted data for meta-analysis. RESULTS: The review included 2,530 randomly assigned participants in 30 trials, most of them short-term. Clozapine-treated patients showed more clinical improvement and experienced significantly fewer relapses during treatment, although the risk of blood dyscrasias in long-term treatment may be as high as 7%. Scores on symptom rating scales showed greater improvement among cloz...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.156.7.990

Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials.

Summary of ﬁndings for the main comparison CLOZAPINE versus TYPICAL ANTIPSYCHOTICS -OVERALL for schizophrenia; Summary of ﬁndings 2 CLOZAPINEversusTYPICALANTIPSYCHOTICS forpeoplewithschizophreniawhose illnesshasprovedresistant totreatment1. COMPARISON 1. CLOZAPINE versus TYPICAL AN-TIPSYCHOTIC DRUGS - OVERALLAll data are derived from 50 studies.1.1 DeathFour deathsoccurredin614peopletreatedwithtypicalneurolep-tics compared with three deaths in 629 people treatedwith cloza-pine. There were no signiﬁcant differences in mortality betweengroups (n=1243, 12 RCTs, RR 0.56 CI 0.1 to 2.3).1.2 Relapse rateWe included 19 short-term studies, and found incidences of re-lapse werelowerin theclozapine group (n=1303, RR 0.62 CI0.5to0.8,NNT21CI15to49)comparedwithtypicalantipsychoticdrugs. Long-term data (4 RCTs, n=578) also favoured clozapinebut data were heterogeneous (I-squared =76%) (RR 0.22 CI 0.1to 0.3).1.3 Global impression1.3.1 Clinical improvement as deﬁned by study authorsWefound thatthenumber ofparticipants whohadnot improvedwere lower in the clozapine group (n=1119, 14 RCTs, RR 0.72CI 0.7 to 0.8, NNT 6 CI 5 to 8). Three long-term studies alsofavoured clozapine (n=719, RR 0.81 CI 0.7 to 0.9) but the dataare heterogeneous (I-squared statistic 81%).1.3.2 Readiness for hospital dischargeThere were no signiﬁcant differences between treatment groupsfor the number of participants who were judged to be not readyfordischarge(short-term,n=447,5RCTs,RR0.88CI0.8to1.0).Long-termdataalsofailedtoshowasigniﬁcant difference(n=648,2 RCTs, RR 0.82 CI 0.6 to 1.1).1.4 Hospitalisation - Not discharged or readmitted within oneyear after dischargeData were available from two long-term studies (Essock 1996(H/CPZ/Flu),Rosenheck1993(H)),andwefoundnosigniﬁcantadvantageforclozapine(n=648,RR0.94CI0.9to1.0)comparedwith typical antipsychotic drugs.1.5 Unable to workWe found no signiﬁcant difference in the number of participantswho were assessed as being unable to work (n=416, 4 RCTs, RR0.87CI0.8to1.0),althoughthedatasuggestedatrendfavouringclozapine (p=0.06).1.6 Participant dissatisfactionNosigniﬁcantdifferenceswerefoundfordissatisfactionwithtreat-mentintwoshort-termstudies(n=114,RR0.72CI0.4to1.3).Wefoundlonger-termdatain(Rosenheck1993(H)).Thesefavouredtheclozapinegroupwhowerelessdissatisﬁedwiththeirtreatmentcomparedwithconventionalantipsychoticdrugs(n=423,RR0.45CI 0.3 to 0.8, NNT 13 CI 9 to 37).1.7 Leaving the study early - acceptability of treatmentWe used leaving the study early data as a proxy measure for theacceptability of treatment. Short-term data from 32 studies in-volving 2316 participants indicated that signiﬁcantly more par-ticipantsgivenclozapinefoundtreatmentacceptable(RR0.81CI0.7 to 1.0, NNT 35 CI 20 to 217). Longer-term data from sixstudies showed a signiﬁcant beneﬁt in the clozapine group (n=982,RR0.60CI0.5to0.7,NNT15CI12to20).Thelong-termattrition rate fromclozapine treatment isapproximately 33% and56% when treated with typical antipsychotic drugs.1.8 Mental state1.8.1 BPRS and PANSSWe found BPRS mental state scores favoured clozapine duringshort-termassessmentin16studies(n=1205,WMD-3.79CI-4.9to -2.7), although the data were heterogeneous (I squared=69%).Longer-term BPRS data (Lee 1994 (mainly H)) were equivocal(n=52, WMD 0.80 CI -5.7 to 7.3). PANSS scores from threeChinesetrialsfavouredtheclozapinegroups(n=163,WMD-3.82CI -7.4 to -0.3) during short-term analysis. Also, PANSS scoresassessed over the long-term favoured clozapine (Rosenheck 1993(H), n=235, WMD -6.90 CI -10.7 to -3.1).1.8.2 Negative symptomsShort-termcontinuous data on negative symptom scores from sixshort-termtrialswith236participantsfavouredclozapine(SANS,WMD -7.12 CI -8.8 to -5.5) but these are heterogeneous data(Isquared=92%). Longer-termnegativesymptomsscoresassessedwiththePANSSnegativesubscorewerenotsigniﬁcantlydifferent(Rosenheck 1993 (H), n=235, WMD -0.90 CI -6.6 to 4.8).1.8.3 Positive symptomsWe found short-term SAPS scores were equivocal (Wang 2001(CPZ), n=60, WMD 4.39 CI -12.2 to 20.9). Longer-term datafrom the PANSS positive scores favoured clozapine (Rosenheck1993 (H), n=235, WMD -2.20 CI -3.3 to -1.1).1.9 Cognitive functionCognitive impairment from one small study (n=82) favoured theclozapine group who experienced less impairment (Klieser 1990(H),RR0.56CI0.3to0.9,NNT4CI3to21)whenassessedwiththe SKT scale compared with those given typical antipsychoticdrugs.Onesmallstudy(Lee1994(mainlyH),n=54)reporteddataon aseriesof cognitive functioning tests(verbal,memory or exec-utive functions etc.) and we found outcomes to be equivocal, ex-cept for ’psychomotor speedand attention’ scoreswhich favouredthe clozapine-treated participants over the three pre-stated cut-off points (short-term, WMD 1.40 CI 0.2 to 2.6, medium-term,WMD1.30CI0.01to3.0,long-term,WMD2.10CI0.8to3.4).Clozapine versus typical neuroleptic medication for schizophrenia (Review)

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Clozapine versus typical neuroleptic medication for schizophrenia.

There has been a decline in the mortality rate among infants and children under five years of age in the last decade in many developing countries. This has led to a shift in focus to look beyond su...

Use of M-CHAT for a multinational screening of young children with autism in the Arab countries.

Background
Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in patients with heart failure and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels and preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted.

Objectives
To review the safety and efficacy of coenzyme Q10 in heart failure.

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. We applied no language restrictions.

Selection criteria
We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in patients with heart failure. When cross-over studies were identified, we considered data only from the first phase.

Data collection and analysis
Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review Manager 5.2 for analysis. We assessed study risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data, we calculated the risk ratio and for continuous data the mean difference (MD). Where appropriate data were available, we performed meta-analysis. For this review we prioritised data from pooled analyses only. Where meta-analysis was not possible, we wrote a narrative synthesis. We provided a QUOROM flow chart to show the flow of papers.

Main results
We included seven studies with 914 participants comparing conenzyme Q10 versus placebo. There were no data on clinical events from published randomised trials. The included studies had small sample sizes. Meta-analysis was only possible for a few physiological measures and there was substantial heterogeneity.

Only one study reported on total mortality, major cardiovascular events and hospitalisation. Five trials reported on the New York Heart Association (NYHA) classification of clinical status, but it was impossible to pool data due to heterogeneity. None of the included trials considered quality of life, exercise variables, adverse events or cost-effectiveness as outcome measures. Pooled analysis suggests that the use of coenzyme Q10 has no clear effect on left ventricular ejection fraction (MD -2.26; 95% confidence interval (CI) -15.49 to 10.97, n = 60) or exercise capacity (MD 12.79; 95% CI -140.12 to 165.70, n = 85). Pooled data did indicate that supplementation increased blood levels of coenzyme Q10 (MD 1.46; 95% CI 1.19 to 1.72, n = 112). However, there are only a small number of small studies with a risk of bias, so these results should be interpreted with caution.

Authors' conclusions
No conclusions can be drawn on the benefits or harms of coenzyme Q10 in heart failure at this time as trials published to date lack information on clinically relevant endpoints. Furthermore, the existing data are derived from small, heterogeneous trials that concentrate on physiological measures: their results are inconclusive. Until further evidence emerges to support the use of coenzyme Q10 in heart failure, there might be a need to re-evaluate whether further trials testing coenzyme Q10 in heart failure are desirable.

Coenzyme Q10 for heart failure

BACKGROUND Tardive dyskinesia is a disfiguring movement disorder of the orofacial region often caused by antipsychotic drugs. A wide range of strategies has been used to help manage tardive dyskinesia and, for people who are unable to have their antipsychotic medication stopped or substantially changed, the calcium-channel blocking group of drugs (diltiazem, nifedipine, nimodipine, verapamil) has been suggested as a useful adjunctive treatment. OBJECTIVES To determine the effects of calcium-channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH STRATEGY We updated previous searches of the Cochrane Schizophrenia Group Register (1982-2000), Cochrane Library (Issue 4, 2000), Cochrane Schizophrenia Group's register of trials (November 2000), EMBASE (1980-2000), LILACS (1982-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), and SCISEARCH by searching the Cochrane Schizophrenia Group Register (September 2003). We searched references of all identified studies for further trial citations and contacted authors of trials. SELECTION CRITERIA Randomised clinical trials comparing calcium-channel blockers to placebo or no intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness. DATA COLLECTION AND ANALYSIS Data were to have been independently extracted and analysed on an intention-to-treat basis. The relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were to have been calculated using a random effects model, and, where possible, the number needed to treat calculated. Weighted mean differences (WMD) were to have been calculated for continuous data. MAIN RESULTS No trials were included. We excluded fourteen studies; eight were not randomised, one did not use calcium channel blockers and five small, randomised, studies reported no usable data. REVIEWER'S CONCLUSIONS The effects of calcium-channel blockers for antipsychotic induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well designed randomised studies.

Adib Essali

Papers

Evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials.

Clozapine versus typical neuroleptic medication for schizophrenia.

Use of M-CHAT for a multinational screening of young children with autism in the Arab countries.

Coenzyme Q10 for heart failure

Calcium channel blockers for neuroleptic‐induced tardive dyskinesia