Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias.

BACKGROUND: Cognitive-behavioural therapy (CBT) is considered to be effective for the symptoms of schizophrenia. However, this view is based mainly on meta-analysis, whose findings can be influenced by failure to consider sources of bias. AIMS: To conduct a systematic review and meta-analysis of the effectiveness of CBT for schizophrenic symptoms that includes an examination of potential sources of bias. METHOD: Data were pooled from randomised trials providing end-of-study data on overall, positive and negative symptoms. The moderating effects of randomisation, masking of outcome assessments, incompleteness of outcome data and use of a control intervention were examined. Publication bias was also investigated. RESULTS: Pooled effect sizes were -0.33 (95% CI -0.47 to -0.19) in 34 studies of overall symptoms, -0.25 (95% CI -0.37 to -0.13) in 33 studies of positive symptoms and -0.13 (95% CI -0.25 to -0.01) in 34 studies of negative symptoms. Masking significantly moderated effect size in the meta-analyses of overall symptoms (effect sizes -0.62 (95% CI -0.88 to -0.35) v. -0.15 (95% CI -0.27 to -0.03), P = 0.001) and positive symptoms (effect sizes -0.57 (95% CI -0.76 to -0.39) v. -0.08 (95% CI -0.18 to 0.03), P<0.001). Use of a control intervention did not moderate effect size in any of the analyses. There was no consistent evidence of publication bias across different analyses. CONCLUSIONS: Cognitive-behavioural therapy has a therapeutic effect on schizophrenic symptoms in the 'small' range. This reduces further when sources of bias, particularly masking, are controlled for.

The UK Divide: Does Having a Pembrolizumab-Chemotherapy Option in Head and Neck Cancer Matter? Real-world Experience of First-line Palliative Pembrolizumab Monotherapy and Pembrolizumab-Chemotherapy Combination in Scotland.

AIMS: The Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence, who approved monotherapy alone in England and Wales. The aim of this study was to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma in the palliative setting in Scotland. MATERIALS AND METHODS: We analysed the electronic records of patients who started pembrolizumab-containing treatment between 1 March 2020 and 30 September 2021. Outcomes included overall survival, progression-free survival (PFS), the duration of response and the disease control rate. Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival. RESULTS: Our cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to those in the KEYNOTE-048 study, although our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease. For patients receiving monotherapy (n = 76), 12- and 24-month overall survival were 45% and 27%, respectively. For patients receiving pembrolizumab-chemotherapy (n = 15), 12-month overall survival was 60% (24-month overall survival had not yet been reached). Experiencing one or more immune-related adverse event (irAE; versus no irAEs), of any grade, was associated with favourable overall survival and PFS for patients receiving monotherapy in both univariable Log-rank analysis (median overall survival 17.4 months versus 8.6 months, respectively, P = 0.0033; median PFS 10.9 months versus 3.0 months, respectively, P < 0.0001) and multivariable analysis (Cox proportional hazards regression: overall survival hazard ratio 0.31, P = 0.0009; PFS hazard ratio 0.17, P < 0.0001). CONCLUSION: Our real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show that irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing that irAEs are generally a positive marker of programmed death-ligand 1 (PD-L1) inhibitor response.

A critique of narrative reviews of the evidence-base for ECT in depression.

There has been recent debate regarding the efficacy of electroconvulsive therapy in the treatment of depression. This has been based on narrative reviews that contradict existing systematic reviews and meta-analyses. In this special article, we highlight the mistakes that occur when interpreting evidence using narrative reviews, as opposed to conventional systematic reviews and meta-analyses.

Intensity-modulated Radiotherapy for Rectal Cancer in the UK in 2020.

AIMS: Preoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of intensity-modulated radiotherapy (IMRT) for rectal cancer is increasing in the UK. However, the extent of IMRT implementation and current practice was not previously known. A national survey was commissioned to investigate the landscape of IMRT use for rectal cancer and to inform the development of national rectal cancer IMRT guidance. MATERIALS AND METHODS: A web-based survey was developed by the National Rectal Cancer IMRT Guidance working group in collaboration with the Royal College of Radiologists and disseminated to all UK radiotherapy centres. The survey enquired about the implementation of IMRT with a focus on the following aspects of the workflow: dose fractionation schedules and use of a boost; pre-treatment preparation and simulation; target volume/organ at risk definition; treatment planning and treatment verification. A descriptive statistical analysis was carried out. RESULTS: In total, 44 of 63 centres (70%) responded to the survey; 30/44 (68%) and 36/44 (82%) centres currently use IMRT to treat all patients and selected patients with rectal cancer, respectively. There was general agreement concerning several aspects of the IMRT workflow, including patient positioning, use of intravenous contrast and bladder protocols. Greater variation in practice was identified regarding rectal protocols; use of a boost to primary/nodal disease; target volume delineation; organ at risk delineation and dose constraints and treatment verification. Delineation of individual small bowel loops and daily volumetric treatment verification were considered potentially feasible by most centres. CONCLUSION: This survey identified that IMRT is already used to treat rectal cancer in many UK radiotherapy centres, but there is heterogeneity between centres in its implementation and practice. These results have been a valuable aid in framing the recommendations within the new National Rectal Cancer IMRT Guidance.

Cognitive behavioural therapy for major psychiatric disorder: does it really work? A meta-analytical review of well-controlled trials.

BACKGROUND: Although cognitive behavioural therapy (CBT) is claimed to be effective in schizophrenia, major depression and bipolar disorder, there have been negative findings in well-conducted studies and meta-analyses have not fully considered the potential influence of blindness or the use of control interventions. METHOD: We pooled data from published trials of CBT in schizophrenia, major depression and bipolar disorder that used controls for non-specific effects of intervention. Trials of effectiveness against relapse were also pooled, including those that compared CBT to treatment as usual (TAU). Blinding was examined as a moderating factor. RESULTS: CBT was not effective in reducing symptoms in schizophrenia or in preventing relapse. CBT was effective in reducing symptoms in major depression, although the effect size was small, and in reducing relapse. CBT was ineffective in reducing relapse in bipolar disorder. CONCLUSIONS: CBT is no better than non-specific control interventions in the treatment of schizophrenia and does not reduce relapse rates. It is effective in major depression but the size of the effect is small in treatment studies. On present evidence CBT is not an effective treatment strategy for prevention of relapse in bipolar disorder.

Facial emotion processing in schizophrenia: a non-specific neuropsychological deficit?

BACKGROUND: Identification of facial emotions has been found to be impaired in schizophrenia but there are uncertainties about the neuropsychological specificity of the finding. METHOD: Twenty-two patients with schizophrenia and 20 healthy controls were given tests requiring identification of facial emotion, judgement of the intensity of emotional expressions without identification, familiar face recognition and the Benton Facial Recognition Test (BFRT). The schizophrenia patients were selected to be relatively intellectually preserved. RESULTS: The patients with schizophrenia showed no deficit in identifying facial emotion, although they were slower than the controls. They were, however, impaired on judging the intensity of emotional expression without identification. They showed impairment in recognizing familiar faces but not on the BFRT. CONCLUSIONS: When steps are taken to reduce the effects of general intellectual impairment, there is no deficit in identifying facial emotions in schizophrenia. There may, however, be a deficit in judging emotional intensity. The impairment found in naming familiar faces is consistent with other evidence of semantic memory impairment in the disorder.

The neuropsychology of the schizo-obsessive subtype of schizophrenia: a new analysis.

BACKGROUND: Interest in the neuro-cognitive profile of patients with schizophrenia and co-morbid obsessive compulsive disorder (schizo-OCD) is rising in response to reports of high co-morbidity rates. Whereas schizophrenia has been associated with global impairment in a wide range of neuro-cognitive domains, OCD is associated with specific deficits featuring impaired performance on tasks of motor and cognitive inhibition involving frontostriatal neuro-circuitry. METHOD: We compared cognitive function using the CANTAB battery in patients with schizo-OCD (n=12) and a schizophrenia group without OCD symptoms (n=16). The groups were matched for IQ, gender, age, medication, and duration of illness. RESULTS: The schizo-OCD patients made significantly more errors on a task of attentional set-shifting (ID-ED set-shift task). By contrast, no significant differences emerged on the Stockings of Cambridge task, the Cambridge Gamble Task or the Affective Go/NoGo tasks. No correlation emerged between ID-ED performance and severity of schizophrenia, OCD or depressive symptoms, consistent with neurocognitive impairment holding trait rather than state-marker status. Schizo-obsessives also exhibited a trend toward more motor tics emphasizing a neurological contribution to the disorder.ConclusionOur findings reveal a more severe attentional set-shifting deficit and neurological abnormality that may be fundamental to the neuro-cognitive profile of schizo-OCD. The clinical implications of these impairments merit further exploration in larger studies.

High-Throughput Phenotyping of Dynamic Canopy Traits Associated with Stay-Green in Grain Sorghum.

Drought is a recurring phenomenon that puts crop yields at risk and threatens the livelihoods of many people around the globe. Stay-green is a drought adaption phenotype found in sorghum and other cereals. Plants expressing this phenotype show less drought-induced senescence and maintain functional green leaves for longer when water limitation occurs during grain fill, conferring benefits in both yield per se and harvestability. The physiological causes of the phenotype are postulated to be water saving through mechanisms such as reduced canopy size or access to extra water through mechanisms such as deeper roots. In sorghum breeding programs, stay-green has traditionally been assessed by comparing visual scores of leaf senescence either by identifying final leaf senescence or by estimating rate of leaf senescence. In this study, we compared measurements of canopy dynamics obtained from remote sensing on two sorghum breeding trials to stay-green values (breeding values) obtained from visual leaf senescence ratings in multienvironment breeding trials to determine which components of canopy development were most closely linked to the stay-green phenotype. Surprisingly, canopy size as estimated using preflowering canopy parameters was weakly correlated with stay-green values for leaf senescence while postflowering canopy parameters showed a much stronger association with leaf senescence. Our study suggests that factors other than canopy size have an important role in the expression of a stay-green phenotype in grain sorghum and further that the use of UAVs with multispectral sensors provides an excellent way of measuring canopy traits of hundreds of plots grown in large field trials.

[A theoretical review of category-specific impairment, its entity and the methodological problems associated with its study]. / Revisión teórica del deterioro categorial, su entidad y los problemas metodológicos asociados a su estudio.

INTRODUCTION: Studies on category-specific claim to provide insights on structure and organization of semantic information. This type of phenomenon consists of the selective impairment of the information on a domain, for instance, living things (animals) but the sparing of nonliving things (tools), or vice versa. Despite the large number of studies purportedly documenting double dissociations between both domains, the lack of theoretical debate on how to empirically define such dissociations is unclear, e.g. how they should be evaluated and reported. DEVELOPMENT: In this work, a review of literature on category-specific and the explanatory models is showed. A critical methodological is done, on the basis of three findings: 1) lack of normal control groups in the majority of case studies; 2) the questionable utilization of double dissociations; and 3) the presence of problems due to a 'ceiling effect' in most group studies of Alzheimer disease patients. CONCLUSIONS: It is claimed that while domain specificity may be a legitimate phenomenon, the critical review of literature do not provide a strong empirical foundation for the domain fractionations claimed in this literature.

A reactive oxygen species-generating, cyclooxygenase-2 inhibiting, cancer stem cell-potent tetranuclear copper(ii) cluster.

Tetranuclear copper(ii) complexes containing multiple diclofenac and Schiff base moieties, 1-4, are shown to kill bulk cancer cells and cancer stem cells (CSCs) with low micromolar potency. The most effective complex, 1, elicits its cytotoxic effect by elevating the intracellular reactive oxygen species (ROS) levels and inhibiting cyclooxygenase-2 (COX-2) expression.

Examining the elemental contribution towards the biodegradation of Mg-Zn-Ca ternary metallic glasses.

The Mg-Zn-Ca metallic glass system has been the focus of recent studies as a prospective material for biodegradable implants. To date, the influence each alloying element has on the degradation behaviour of this class of alloy is still not well understood. This study employs electrochemical polarisation and in situ impedance spectroscopy coupled with H2 gas collection in simulated body fluid at 37 °C to elucidate the mechanisms by which a series of custom produced Mg-Zn-Ca metallic glasses degrade compared with high purity Mg. The results show that Mg-Zn-Ca metallic glasses provide significantly more noble corrosion potentials and suppressed hydrogen gas evolution relative to high purity Mg. Furthermore, the role each element has in degradation was investigated systematically by varying the concentration of each alloying element. Testing revealed that the complex nature of dissolution in metallic glasses requires testing beyond solely polarisation and hydrogen gas collection to elucidate degradation behaviour in vitro. Practical limits to which the composition may be adjusted in this ternary alloy system, so as to maintain minimal degradation, have been achieved.

A predictive structural model for bulk metallic glasses.

Great progress has been made in understanding the atomic structure of metallic glasses, but there is still no clear connection between atomic structure and glass-forming ability. Here we give new insights into perhaps the most important question in the field of amorphous metals: how can glass-forming ability be predicted from atomic structure? We give a new approach to modelling metallic glass atomic structures by solving three long-standing problems: we discover a new family of structural defects that discourage glass formation; we impose efficient local packing around all atoms simultaneously; and we enforce structural self-consistency. Fewer than a dozen binary structures satisfy these constraints, but extra degrees of freedom in structures with three or more different atom sizes significantly expand the number of relatively stable, 'bulk' metallic glasses. The present work gives a new approach towards achieving the long-sought goal of a predictive capability for bulk metallic glasses.

A normal' category-specific advantage for naming living things.

'Artefactual' accounts of category-specific disorders for living things have highlighted that compared to nonliving things, living things have lower name frequency, lower concept familiarity and greater visual complexity and greater within-category structural similarity or 'visual crowding' [7]. These hypotheses imply that deficits for living things are an exaggeration of some 'normal tendency'. Contrary to these notions, we found that normal subjects were consistently worse at naming nonliving than living things in a speeded presentation paradigm. Moreover, their naming was not predicted by concept familiarity, name frequency or visual complexity; however, a novel measure of visual familiarity (i.e. for the appearance of things) did significantly predict naming. We propose that under speeded conditions, normal subjects find nonliving things harder to name because their representations are less visually predictable than for living things (i.e. nonliving things show greater within-item structural variability). Finally, because nonliving things have multiple representations in the real world, this may lower the probability of finding impaired naming and recognition in this category.