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Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson’s disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.

Objective This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new‐onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30‐day mortality and cause of death are also reported. Methods Children living with HIV (CLWHIV) with new‐onset seizures were prospectively evaluated at one large urban teaching hospital and two non‐urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. Results From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2‐10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non‐accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty‐two (30%) children died within 30 days of the index seizure. Significance Despite widespread ART roll out in Zambia, new‐onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Background Dementia is a growing global public health challenge. Previous meta‐analyses have found that systemic medications may modulate dementia risk. We aimed to provide an overview of this evidence. Method We conducted an umbrella review of meta‐analyses (PROSPERO CRD42021226307). MEDLINE, AMED, PsycINFO, and Embase were searched from inception to 25th January 2023. Only peer‐reviewed meta‐analyses examining dementia risk and systemic medications in humans were included, with no restrictions on language. Studies examining cognitive decline were excluded. Participant details, study types, diagnostic criteria, publication bias, heterogeneity, and summary effect estimates were extracted from publications. Study quality was assessed using the AMSTAR‐2. Data extraction and quality ratings were carried out independently by two authors. Result 60 studies were included in the final review. Included meta‐analyses examined anti‐hypertensives (n = 17), statins (n = 7), antacids (n = 7), non‐steroidal anti‐inflammatory drugs (NSAIDs) (n = 6), diabetes medications (n = 4), hormone replacement therapy (n = 4), androgen deprivation therapy (ADT) (n = 4), psychotropic medications (n = 4), anticholinergics (n = 3), anticoagulants (n = 2), and vitamin E (n = 2). Number of participants in each review ranged from 842 to 9,162,509. Mean age ranged from 59 to 78 years, and between 0 and 100% of participants were female. There was a trend towards decreased risk of dementia with antihypertensives, statins, NSAIDs, anticoagulants, and vitamin E, and towards increased risk with ADT, benzodiazepines, and anticholinergic medications. Conclusion Available data were primarily observational, leading to biases such as confounding by indication, and few studies met a high number of critical quality criteria. Randomised‐controlled data were rare but supported an association between treatment of hypertension and reduced dementia incidence and a possible association between hormone replacement therapy and increased risk of dementia. Our review provides an overview of what kinds of medication are associated with dementia risk, to guide clinical practice and future research. Currently there are no systemic medications that should be prescribed with the primary aim of reducing dementia risk.

Normal pressure hydrocephalus (NPH) is a treatable but potentially under-diagnosed condition causing dementia. At presentation, half of people with NPH score in the dementia range on formal testing, and 75% have cognitive impairment. However, little is known about NPH in memory services. Here, we describe recorded NPH in a large, ethnically and socioeconomically diverse memory service cohort for the first time. South London and Maudsley (SLAM) NHS Trust in England has a catchment of 1.3 million residents. All people aged 60 years and above referred to memory services in SLAM from 01/01/2008 to 22/02/2025 were included. We extracted data on age, sex, ethnicity, neighbourhood-level deprivation, cognitive test results, dementia diagnosis, and location from SLAM's Clinical Record Interactive Search (CRIS) system, national death certification data, and from Hospital Episode Statistics (HES), which records data on all hospital diagnoses in England. Diagnosis of NPH was defined as any recorded code of ICD10 G91.2. 74 diagnoses of G91.2 were recorded (n =26,322). Mean age was lower in people with recorded NPH (76.60 years, standard deviation (SD): 6.61), compared to the source cohort (79.03, SD: 8.72) (see Figure 1). More people with recorded NPH were male (68.92%) compared to the source memory clinic population (41.17%). Mean Addenbrookes' Cognitive Examination (ACE) score was lower among people with recorded NPH (61.97, SD: 15.36) than the source cohort (67.18, SD: 17.53). Our findings could reflect under-diagnosis of NPH in memory services. Recorded diagnosis of NPH in our population was rare, with a 17-year case proportion of 0.28%. Other studies have estimated the point prevalence of NPH in the general population above 60 years old to be 0.45% and, though our measure is not directly comparable, we expected a higher number of cases in this clinical population with cognitive symptoms. We focussed on recorded diagnosis of G91.2, which may have limited our results due to inconsistent diagnostic code use. These findings warrant further work including investigating the chronology of diagnosis with memory clinic referral and investigation of alternative ICD10 codes used for NPH in this population.

Background Normal pressure hydrocephalus (NPH) is a treatable but potentially under‐diagnosed condition causing dementia. At presentation, half of people with NPH score in the dementia range on formal testing, and 75% have cognitive impairment. However, little is known about NPH in memory services. Here, we describe recorded NPH in a large, ethnically and socioeconomically diverse memory service cohort for the first time. Method South London and Maudsley (SLAM) NHS Trust in England has a catchment of 1.3 million residents. All people aged 60 years and above referred to memory services in SLAM from 01/01/2008 to 22/02/2025 were included. We extracted data on age, sex, ethnicity, neighbourhood‐level deprivation, cognitive test results, dementia diagnosis, and location from SLAM’s Clinical Record Interactive Search (CRIS) system, national death certification data, and from Hospital Episode Statistics (HES), which records data on all hospital diagnoses in England. Diagnosis of NPH was defined as any recorded code of ICD10 G91.2. Result 74 diagnoses of G91.2 were recorded (n =26,322). Mean age was lower in people with recorded NPH (76.60 years, standard deviation (SD): 6.61), compared to the source cohort (79.03, SD: 8.72) (see Figure 1). More people with recorded NPH were male (68.92%) compared to the source memory clinic population (41.17%). Mean Addenbrookes’ Cognitive Examination (ACE) score was lower among people with recorded NPH (61.97, SD: 15.36) than the source cohort (67.18, SD: 17.53). Conclusion Our findings could reflect under‐diagnosis of NPH in memory services. Recorded diagnosis of NPH in our population was rare, with a 17‐year case proportion of 0.28%. Other studies have estimated the point prevalence of NPH in the general population above 60 years old to be 0.45% and, though our measure is not directly comparable, we expected a higher number of cases in this clinical population with cognitive symptoms. We focussed on recorded diagnosis of G91.2, which may have limited our results due to inconsistent diagnostic code use. These findings warrant further work including investigating the chronology of diagnosis with memory clinic referral and investigation of alternative ICD10 codes used for NPH in this population.

Background Brain imaging data for dementia research have historically been derived from highly selected groups, leading to potentially misleading norms. Here, we aimed to describe broad imaging‐derived phenotypes, including global white‐matter hyperintensities (WMH) volume, in an ethnically and socio‐economically diverse real‐world memory clinic population for the first time. Method Our population comprised people aged 60 years plus with at least one referral to memory services and an available brain MRI in the South London and Maudsley (SLAM) NHS Trust in England. We extracted routine clinical data on age, sex, ethnicity, and socioeconomic deprivation. Routinely‐collected brain MRIs were identified through the SLAM ImageBank. Images were segmented with SynthSeg and WMH‐SynthSeg. All volumetric measures were adjusted by total intracranial volume. We examined available regions of interest of apriori relevance to dementia and to understanding ventricular dynamics in the future, in relation to WMH volume. Result Our final sample included 4,311 MPRAGE and 4,285 FLAIR scans. Mean age was 75.6 years (standard deviation (SD) 7.8), 57% were female. A majority (67%) of the population lived in areas at or below the median for national deprivation. 59% of the population identified as White, 21% as Black, 10% as Asian, and 10% as Other. Distributions of selected volumes are shown in Figure 1. Hippocampal volumes were positively correlated with cerebral cortical volumes (rho: 0.36 to 0.41) (Figure 2), but inversely related to lateral ventricular volumes (rho: ‐0.57 to ‐0.56), and this persisted after adjustment for extra‐axial cerebrospinal fluid (CSF) (rho: ‐0.41). Total WMH volume was positively correlated with lateral ventricular volumes (rho: 0.42) but not with total CSF (rho: ‐0.12) or cortical volumes (rho: ‐0.18 to ‐0.17). Conclusion In general we found that volume of WMH was positively correlated with intra‐axial CSF volumes but inversely related to cortical volumes. Hippocampal and cortical volumes were inversely correlated with CSF, as expected. Improving our understanding of imaging‐derived phenotypes in routine clinical populations is crucial to the generalisability and applicability of potential future treatments for dementia. These results will form the basis for developing normative models including WMH data in a large‐scale representative clinical population.

Brain imaging data for dementia research have historically been derived from highly selected groups, leading to potentially misleading norms. Here, we aimed to describe broad imaging-derived phenotypes, including global white-matter hyperintensities (WMH) volume, in an ethnically and socio-economically diverse real-world memory clinic population for the first time. Our population comprised people aged 60 years plus with at least one referral to memory services and an available brain MRI in the South London and Maudsley (SLAM) NHS Trust in England. We extracted routine clinical data on age, sex, ethnicity, and socioeconomic deprivation. Routinely-collected brain MRIs were identified through the SLAM ImageBank. Images were segmented with SynthSeg and WMH-SynthSeg. All volumetric measures were adjusted by total intracranial volume. We examined available regions of interest of apriori relevance to dementia and to understanding ventricular dynamics in the future, in relation to WMH volume. Our final sample included 4,311 MPRAGE and 4,285 FLAIR scans. Mean age was 75.6 years (standard deviation (SD) 7.8), 57% were female. A majority (67%) of the population lived in areas at or below the median for national deprivation. 59% of the population identified as White, 21% as Black, 10% as Asian, and 10% as Other. Distributions of selected volumes are shown in Figure 1. Hippocampal volumes were positively correlated with cerebral cortical volumes (rho: 0.36 to 0.41) (Figure 2), but inversely related to lateral ventricular volumes (rho: -0.57 to -0.56), and this persisted after adjustment for extra-axial cerebrospinal fluid (CSF) (rho: -0.41). Total WMH volume was positively correlated with lateral ventricular volumes (rho: 0.42) but not with total CSF (rho: -0.12) or cortical volumes (rho: -0.18 to -0.17). In general we found that volume of WMH was positively correlated with intra-axial CSF volumes but inversely related to cortical volumes. Hippocampal and cortical volumes were inversely correlated with CSF, as expected. Improving our understanding of imaging-derived phenotypes in routine clinical populations is crucial to the generalisability and applicability of potential future treatments for dementia. These results will form the basis for developing normative models including WMH data in a large-scale representative clinical population.

Psychedelics are emerging as potential treatments for neuropsychiatric conditions, with evidence suggesting a single administration can lead to enduring behavioural changes. While the underlying putative mechanism(s) remain unclear, there is evidence supporting altered learning as a key candidate. This systematic review examined studies assessing the effects of psychedelics on associative learning in both humans and animals. Electronic databases were searched up until 13/01/2025 for studies investigating any difference in learning after psychedelic administration. 31 studies were included (29 in animals, 2 in humans). Classical and operant conditioning paradigms were employed, including fear extinction, conditioned avoidance, and reversal learning. Studies assessed acute and post-acute effects, however repeated dosing paradigms often obscured this distinction. There was considerable heterogeneity in study designs, paradigms, drug administration timings and doses, and behavioural effects appeared to be influenced by dose, timing, training intensity, and sex. Due to between-study heterogeneity, a meta-analysis was not possible. Evidence suggests that psychedelic administration enhances associative learning in animals across paradigms, although findings were not entirely consistent. Possible mechanisms identified were increased prediction error sensitivity, serotonin receptor agonism, and structural plasticity. Learning enhancements may extend into the post-acute phase and appear to depend on active environmental engagement during this window. Studies suggest that psychedelics enhance associative learning in animals; however, these findings are yet to be translated into humans. Understanding whether a period of enhanced learning follows the psychedelic experience may have important implications for psychedelic-assisted psychotherapy, where behavioural changes must generalise and persist beyond the drug-induced state.

The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe. In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing. As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47·4%] were women and 1822 [52·6%] were men, with a median age of 68 years [IQR 57–77]). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0·32 [95% CI 0·19–0·61) and 28 days (0·34 [0·16–0·79]), complications due to COVID-19 (0·26 [0·17–0·46]), and hospitalisation due to COVID-19 (0·17 [0·09–0·32]), and had less requirements for COVID-19-specific therapy (0·22 [0·15–0·34]) and oxygen therapy (0·24 [0·14–0·43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase. Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19. National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.