Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials

The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system. Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome. Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit

Can cognitive insight predict symptom remission in a first episode psychosis cohort?

BACKGROUND: The outcome of first episode psychosis (FEP) is highly variable and difficult to predict. Cognitive insight measured at illness onset has previously been found to predict psychopathology 12-months later. The aims of this study were to examine whether the prospective relationship between cognitive insight and symptom severity is evident at four-years following FEP and to examine some psychological correlates of cognitive insight. METHODS: FEP participants (n = 90) completed the Beck Cognitive Insight Scale (BCIS) at illness onset, and associations between BCIS scores with symptom severity outcomes (4-years after FEP) were assessed. The BCIS scales (self-reflectiveness and self-certainty) were examined as a composite score, and individually compared to other cognitive measures (IQ and jumping to conclusions (JTC) bias). RESULTS: Regression analyses revealed that the cognitive insight composite did not predict 4-year symptom remission in this study while the self-reflection subscale of the BCIS predicted severity of symptoms at 4-years. Self-certainty items of the BCIS were not associated with symptom severity. Significant correlations between the JTC bias, self-certainty and IQ were found, but self-reflection did not correlate with these other cognitive measures. CONCLUSIONS: Self-reflective capacity is a more relevant and independent cognitive construct than self-certainty for predicting prospective symptom severity in psychosis. Improving self-reflection may be a useful target for early intervention research

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Are there specific neuropsychological deficits underlying poor insight in first episode psychosis?

Insight in psychosis is a multi-dimensional phenomenon, and has been hypothesised to have some sort of neuropsychological basis. It is unclear to what extent specific neuropsychological abilities are able to predict insight beyond the effect of generalised cognitive ability. We aimed to test this, alongside the relationship of insight with illness duration and diagnosis, in a sample of first episode psychosis patients. We recruited 102 patients experiencing their first episode of psychosis and assessed their insight, symptoms, diagnosis as well as administering a full neuropsychological battery. Low insight was related to worse performance in a variety of neuropsychological tasks. Regression analysis tested whether any specific tasks were related to insight (or dimensions of insight) beyond the effect of IQ. Verbal memory had an effect on total insight and all dimensions of insight (except compliance) beyond the effect of IQ. Insight appeared to vary with diagnosis, with those diagnosed with depressive affective psychoses having better insight than those with manic affective psychoses. There was no relationship between insight and DUP, but there was a relationship between time spent in treatment before assessment and insight, even after controlling for severity of symptoms. The results taken together suggest a model of insight in early psychosis with a significant neuropsychological component, particularly with verbal memory but also with generalised cognitive ability. There is likely to be a social component to insight affected by initial time spent in contact with treatment, helping patients to understand and come to terms with their illness

Do Psychosis Patients with Poor Insight Show Implicit Awareness on the Emotional Stroop Task?

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The insight into psychosis can be assessed reliably by clinicians from interviews with patients. However, patients may retain implicit awareness of illness while lacking explicit awareness. &lt;b&gt;&lt;i&gt;Sampling and Methods:&lt;/i&gt;&lt;/b&gt; In a sample of first-episode psychosis patients, we used a test of processing of mental illness-related and other negative words as a measure of implicit awareness to see how this varied in relation to insight. An emotional-counting Stroop task tested reaction times to words of three types: psychosis-related (e.g. ‘crazy'), general negative (e.g. ‘cancer') and neutral (e.g. ‘oyster'). Data were available from 43 patients and 23 healthy controls. Patients' insight was assessed using the Schedule for the Assessment of Insight (SAI-E). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Patients reacted slower than controls to words across all conditions, and both patients and controls reacted slower to salient and negative words than neutral words. There was a near significant interaction between word type and group (Wilks' lambda = 0.53, p = 0.055); patients experienced greater interference from negative rather than psychosis-related words (p = 0.003), and controls experienced greater interference from salient rather than negative words (p = 0.01). Within the patient group, there was a correlation between insight and interference on salient words (r = 0.33, p = 0.05), such that those with less insight experienced less interference on psychosis-related words. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Psychosis-related words were less threatening and less self-relevant to psychosis patients with less insight. This suggests that the lack of awareness such patients have of their illness is genuine and more likely to be mediated by lower-level information processing mechanisms than strategies such as conscious, motivated denial.</jats:p