Dopamine partial agonists and prodopaminergic drugs for schizophrenia: Systematic review and meta-analysis of randomized controlled trials.

Dopaminergic dysfunction is thought to be central to schizophrenia symptomatology. Previous meta-analyses of prodopaminergic drugs in schizophrenia have important limitations, and also did not include dopamine D2/D3 partial agonists. We investigated the effect of medications which increase dopamine signalling on schizophrenia symptoms by meta-analysing double-blind, placebo-controlled RCTs. 59 RCTs were included: 29 of prodopaminergic treatments, 30 of partial agonists. Partial agonists were significantly superior to placebo against positive (SMD=-0.33,p = 1.2 ×10-17), negative (SMD=-0.29,p = 2.2 × 10-31) and total symptoms (SMD =-0.39,p = 1.7 × 10-30) in schizophrenia. There were no significant differences between pooled pro-dopaminergic drugs and placebo in any symptom domain. In subgroup analysis of five studies where patients were selected for negative symptom severity, ar/modafinil was superior to placebo against negative symptoms (SMD=-0.34,p = 0.037). These data favour the clinical use of partial agonists for negative symptoms in schizophrenia, with clinically meaningful effect sizes. Our findings also suggest a benefit for ar/modafinil in patients with predominant negative symptoms. Future trials of other prodopaminergic therapies and dopamine partial agonists in patients with predominant negative symptoms are warranted.

The clinical significance of duration of untreated psychosis: an umbrella review and random-effects meta-analysis.

The idea that a longer duration of untreated psychosis (DUP) leads to poorer outcomes has contributed to extensive changes in mental health ser-vices worldwide and has attracted considerable research interest over the past 30 years. However, the strength of the evidence underlying this notion is unclear. To address this issue, we conducted an umbrella review of available meta-analyses and performed a random-effects meta-analysis of primary studies. MEDLINE, Web of Science, PsycINFO and EMBASE were searched from inception to September 3, 2020 to identify relevant meta-analyses of studies including patients with schizophrenia spectrum disorders, first-episode psychosis, or affective and non-affective psychosis. Thirteen meta-analyses were included, corresponding to 129 individual studies with a total sample size of 25,657 patients. We detected potential violations of statistical assumptions in some of these meta-analyses. We therefore conducted a new random-effects meta-analysis of primary studies. The association between DUP and each outcome was graded according to a standardized classification into convincing, highly suggestive, suggestive, weak, or non-significant. At first presentation, there was suggestive evidence for a relationship between longer DUP and more severe negative symptoms (beta=-0.07, p=3.6×10-5 ) and higher chance of previous self-harm (odds ratio, OR=1.89, p=1.1×10-5 ). At follow-up, there was highly suggestive evidence for a relationship between longer DUP and more severe positive symptoms (beta=-0.16, p=4.5×10-8 ), more severe negative symptoms (beta=-0.11, p=3.5×10-10 ) and lower chance of remission (OR=2.16, p=3.0×10-10 ), and suggestive evidence for a relationship between longer DUP and poorer overall functioning (beta=-0.11, p=2.2×10-6 ) and more severe global psychopathology (beta=-0.16, p=4.7×10-6 ). Results were unchanged when analysis was restricted to prospective studies. These effect sizes are clinically meaningful, with a DUP of four weeks predicting >20% more severe symptoms at follow-up relative to a DUP of one week. We conclude that DUP is an important prognostic factor at first presentation and predicts clinically relevant outcomes over the course of illness. We discuss conceptual issues in DUP research and methodological limitations of current evidence, and provide recommendations for future research.

Pre-Operative Imaging can Reduce Negative Appendectomy Rate in Acute Appendicitis.

INTRODUCTION: Acute appendicitis is a common surgical emergency, with a prevalence of 112 per 100,000 people per year in Europe. Negative appendicectomy is defined as a pathologically normal appendix removed from patient suspected with appendicitis. Negative appendectomy rate (NAR) has been reported to be around 15-25%. We aimed to evaluate our unit's negative appendectomy rate and the effect of pre-operative imaging on NAR. METHOD: A retrospective study including all patients who underwent both open and laparoscopic emergency appendicectomy in a single district general hospital from 2017-2018. Clinical information including cost was calculated based on the 2017/18 national tariff payment system. Patients under 18 years old were excluded from this study. RESULTS: Two hundred thirty-two patients were included in this study, of which 69 (29.74%) had a pre-operative CT scan. The mean length of stay was 2.57 days. The sensitivity, specificity, positive predictive value and negative predictive value for CT were 77.8%, 100%, 87.5% and 100%. The negative appendicectomy rate with and without pre-operative CT scan were 7.25% and 22.09% respectively. Based on the 2017/18 national tariff payment system, a CT abdomen and pelvis with contrast and emergency appendicectomy with CC score of 0 cost 92 and 2370 pounds respectively. The total cost of patients who underwent appendicectomy without imaging was £ 322,320. If all patients undergo pre-operative CT, with a reduction of 15% in negative appendicectomy rate, the overall total cost would significantly lower to £ 36,212. CONCLUSION: Our study demonstrated that the negative appendicectomy rate could be improved by preoperative imaging. The study also showed that implementation of preoperative imaging for suspected appendicitis cases could save costs, allowing better allocation of resources.

The 100 most cited manuscripts in coronary artery bypass grafting.

INTRODUCTION: To gain a better understanding of the progression of coronary artery bypass grafting (CABG) and its impact on clinical practice, bibliometric citation analysis can be performed. Bibliometric citation analysis is a method of determining the most influential papers on a topic based on several citations and impact factor. METHOD: A search of the Thomson Reuters Web of Science citation indexing database and research platform was completed using the terms "CABG," "Coronary artery bypass graft," "Coronary artery," "bypass," and/or "bypass grafting." The returned dataset was sorted by the number of citations. RESULTS: The search yielded a total of 11 560 papers which were ranked in order of citations. New England Journal of Medicine published the most papers in the top 100 and generated the most significant number of citations with 20 papers in total followed by Journal of the American College of Cardiology. It also has the highest impact factor and 5-year impact fact in 2007 of 79.26 and 67.513, respectively. CONCLUSION: The most cited manuscripts by Serruys et al described a randomised trial comparing percutaneous coronary intervention and CABG for treating severe coronary artery disease. This work provides the most influential references related to CABG and serves as a guide as to the area of focus in CABG.