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Clozapine-induced gastrointestinal hypomotility (CIGH) can cause constipation, which may progress to ileus, intestinal perforation and other life-threatening conditions. There were at least 527 unique cases of harmful CIGH (172 deaths) assessed by strict criteria in the UK, 1992–2017.
Aims
To assess the impact of strengthened warnings about the risks of CIGH, such as those issued by the UK Medicines and Healthcare products Regulatory Agency (MHRA) (2017) and the US Food and Drug Administration (2020), on reports of harmful CIGH in the UK.
Method
We audited UK MHRA Yellow Card reports recorded as clozapine-related gastrointestinal disorders, 2018–end 2022.
Results
Of 335 unique reports (36 fatal, 26 male) that met initial CIGH criteria, there were 129 (22 fatal, 18 male) that met the final CIGH inclusion criteria. Reports of non-fatal CIGH (final criteria) averaged 26 per year (15 in 2022). Deaths averaged four per year (two in 2022). Where data were available the greatest proportion of deaths occurred after 10–14 years of clozapine treatment.
Conclusions
Publicity aimed at raising awareness of the problem posed by CIGH has been associated with a reduction in harmful CIGH as reported to the UK MHRA since 2017. Continued vigilance is needed to reduce risk. Stopping smoking may pose a particular risk and should be monitored carefully.
Cognitive behavioural therapists and practitioners often feel uncertain about how to treat post-traumatic stress disorder (PTSD) following rape and sexual assault. There are many myths and rumours about what you should and should not do. All too frequently, this uncertainty results in therapists avoiding doing trauma-focused work with these clients. Whilst understandable, this means that the survivor continues to re-experience the rape as flashbacks and/or nightmares. This article outlines an evidence-based cognitive behavioural therapy (CBT) approach to treating PTSD following a rape in adulthood. It aims to be a practical, ‘how to’ guide for therapists, drawing on the authors’ decades of experience in this area. We have included film links to demonstrate how to undertake each step of the treatment pathway. Our aim is for CBT practitioners to feel more confident in delivering effective trauma-focused therapy to this client group. We consider how to assess and formulate PTSD following a rape in adulthood, then how to deliver cognitive therapy for PTSD (CT-PTSD; Ehlers and Clark, 2000). We will cover both client and therapist factors when working with memories of rape, as well as legal, social, cultural and interpersonal considerations.
Key learning aims
To understand the importance of providing effective, trauma-focused therapy for survivors of rape in adulthood who are experiencing symptoms of PTSD.
To be able to assess, formulate and treat PTSD following a rape in adulthood.
How to manage the dissociation common in this client group.
To be able to select and choose appropriate cognitive, behavioural and imagery techniques to help with feelings of shame, responsibility, anger, disgust, contamination and mistrust.
For therapists to learn how best to support their own ability to cope with working in a trauma-focused way with survivors of rape and sexual violence.
Airway management is a cornerstone in the prehospital care of critically ill or injured patients. Surgical cricothyrotomy offers a rapid and effective solution when oxygenation and ventilation fail using less-invasive techniques. However, the exact indications, incidence, and success of prehospital surgical cricothyrotomy are unknown, with variable rates reported in the literature. This study aimed to examine prehospital indications and success rates for surgical cricothyrotomy within a large, suburban, ground-based Emergency Medical Services (EMS) system.
Methods:
This is a retrospective analysis of 31 patients who underwent paramedic performed surgical cricothyrotomy from 2012 through 2022. Key demographic parameters were analyzed, including the incidence of cardiac arrest, call type (trauma versus medical), initial airway management attempts, number of endotracheal intubation (ETI) attempts before surgical airway, and average time to the establishment of a surgical airway in relation to the number of ETI attempts. Surgical cricothyrotomy success was defined as the acquisition of four-phase end-tidal capnography reading. The primary data sources were the EMS electronic medical records, and descriptive statistics were calculated.
Results:
A total of 31 patients were included in the final analysis. Of those who received a surgical cricothyrotomy, 42% (13/31) occurred in the trauma setting, while 58% (18/31) were medical calls. In all patients who underwent surgical cricothyrotomy, the median (IQR) time to the procedure was 17 minutes (IQR = 11-24). In trauma patients, the median time to surgical cricothyrotomy was 12 minutes (IQR = 9-19) versus 19 minutes (IQR = 14-33) in medical patients. End-tidal carbon dioxide (ETCO2) detection and placement success was confirmed in 94% (29/31) of patients. Endotracheal intubation was attempted in 55% (17/31) before subsequent surgical cricothyrotomy, with 29% (9/31) receiving more than one ETI attempt. The median time to surgical cricothyrotomy when multiple prior intubation attempts occurred was 33 minutes (IQR = 23-36) compared to 14.5 minutes (IQR = 6-19) in patients without a preceding intubation attempt.
Conclusion:
Prehospital surgical airway can be performed by paramedics with a high degree of success. Identification of the need for surgical cricothyrotomy should be determined as soon as possible to allow for rapid securement of the airway and to ensure adequate oxygenation and ventilation.
A method for extracting Ni and other metals from lateritic ores by means of shock heating has been investigated. Shock heating releases some of the metal from its goethitic host. Even though the transformation of pure goethite to hematite is known to occur via intermediate hydroxylated phases, the effect of other metals such as Ni substituting for Fe in goethites on this thermal transformation to hematite is unknown. The purpose of this study was to fill this gap, with the hope that the results will lead to more energy-efficient extraction methods and/or a better understanding of Fe geochemistry in thermally activated soils. X-ray diffraction, transmission electron microscopy with EDS, and thermal analysis were used to investigate mineralogical changes in nickeliferous goethites from five oxide-type lateritic nickel ore deposits that had been subjected to shock heating at temperatures in the range 220–800°C. Acicular, nano-sized goethite was the main constituent of the samples with minor to trace amounts of quartz, talc, kaolinite, chromite, maghemite, and Mn oxides. Goethite was partially dehydroxylated to OH-hematite at 340–400°C and had completely altered to well ordered hematite at 800°C. The OH-hematite was characterized by broad XRD peaks for reflections associated with the Fe sublattice. The goethite unit-cell a and b lengths remained almost constant with increasing preheating temperature up to 300°C, while the size of the c axis dimension contracted. The neoformed hematite crystals were larger than the precursor goethite crystals due to development, by sintering and surface diffusion, of regularly ordered hematite domains. The increase (1.5–2.6 fold) in surface area with increasing heating temperature (up to 340–400°C) reflected the development of slit-shaped micropores (∼300°C), which further developed into elliptically shaped micropores (∼400°C) in OH-hematite. With increased heating temperature, well ordered hematite formed with only a few micropores remaining. Such results may contribute to the development of more efficient procedures for extracting Ni from lateritic nickel ores, as the rate of dissolution of goethite in acid in ‘heap and pressure’ leach facilities will be enhanced by the increases in surface area and microporosity. The results may also provide valuable information on the probable effects of natural heating on pedogenic Fe oxides.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
HIV and severe wasting are associated with post-discharge mortality and hospital readmission among children with complicated severe acute malnutrition (SAM); however, the reasons remain unclear. We assessed body composition at hospital discharge, stratified by HIV and oedema status, in a cohort of children with complicated SAM in three hospitals in Zambia and Zimbabwe. We measured skinfold thicknesses and bioelectrical impedance analysis (BIA) to investigate whether fat and lean mass were independent predictors of time to death or readmission. Cox proportional hazards models were used to estimate the association between death/readmission and discharge body composition. Mixed effects models were fitted to compare longitudinal changes in body composition over 1 year. At discharge, 284 and 546 children had complete BIA and skinfold measurements, respectively. Low discharge lean and peripheral fat mass were independently associated with death/hospital readmission. Each unit Z-score increase in impedance index and triceps skinfolds was associated with 48 % (adjusted hazard ratio 0·52, 95 % CI (0·30, 0·90)) and 17 % (adjusted hazard ratio 0·83, 95 % CI (0·71, 0·96)) lower hazard of death/readmission, respectively. HIV-positive v. HIV-negative children had lower gains in sum of skinfolds (mean difference −1·49, 95 % CI (−2·01, −0·97)) and impedance index Z-scores (–0·13, 95 % CI (−0·24, −0·01)) over 52 weeks. Children with non-oedematous v. oedematous SAM had lower mean changes in the sum of skinfolds (–1·47, 95 % CI (−1·97, −0·97)) and impedance index Z-scores (–0·23, 95 % CI (−0·36, −0·09)). Risk stratification to identify children at risk for mortality or readmission, and interventions to increase lean and peripheral fat mass, should be considered in the post-discharge care of these children.
The number of people over the age of 65 attending Emergency Departments (ED) in the United Kingdom (UK) is increasing. Those who attend with a mental health related problem may be referred to liaison psychiatry for assessment. Improving responsiveness and integration of liaison psychiatry in general hospital settings is a national priority. To do this psychiatry teams must be adequately resourced and organised. However, it is unknown how trends in the number of referrals of older people to liaison psychiatry teams by EDs are changing, making this difficult.
Method
We performed a national multi-centre retrospective service evaluation, analysing existing psychiatry referral data from EDs of people over 65. Sites were selected from a convenience sample of older peoples liaison psychiatry departments. Departments from all regions of the UK were invited to participate via the RCPsych liaison and older peoples faculty email distribution lists. From departments who returned data, we combined the date and described trends in the number and rate of referrals over a 7 year period.
Result
Referral data from up to 28 EDs across England and Scotland over a 7 year period were analysed (n = 18828 referrals). There is a general trend towards increasing numbers of older people referred to liaison psychiatry year on year. Rates rose year on year from 1.4 referrals per 1000 ED attenders (>65 years) in 2011 to 4.5 in 2019 . There is inter and intra site variability in referral numbers per 1000 ED attendances between different departments, ranging from 0.1 - 24.3.
Conclusion
To plan an effective healthcare system we need to understand the population it serves, and have appropriate structures and processes within it. The overarching message of this study is clear; older peoples mental health emergencies presenting in ED are common and appear to be increasingly so. Without appropriate investment either in EDs or community mental health services, this is unlikely to improve.
The data also suggest very variable inter-departmental referral rates. It is not possible to establish why rates from one department to another are so different, or whether outcomes for the population they serve are better or worse. The data does however highlight the importance of asking further questions about why the departments are different, and what impact that has on the patients they serve.
Functional benefits of the morphologies described by Bergmann's and Allen's rules in human males have recently been reported. However, the functional implications of ecogeographical patterning in females remain poorly understood. Here, we report the findings of preliminary work analysing the association between body shape and performance in female ultramarathon runners (n = 36) competing in hot and cold environments. The body shapes differed between finishers of hot and cold races, and also between hot race finishers and non-finishers. Variability in race performance across different settings supports the notion that human phenotype is adapted to different thermal environments as ecogeographical patterns have reported previously. This report provides support for the recent hypothesis that the heightened thermal strain associated with prolonged physical activity in hot/cold environments may have driven the emergence of thermally adaptive phenotypes in our evolutionary past. These results also tentatively suggest that the relationship between morphology and performance may be stronger in female vs. male athletes. This potential sex difference is discussed with reference to the evolved unique energetic context of human female reproduction. Further work, with a larger sample size, is required to investigate the observed potential sex differences in the strength of the relationship between phenotype and performance.
Both extinct and extant hominin populations display morphological features consistent with Bergmann's and Allen's Rules. However, the functional implications of the morphologies described by these ecological laws are poorly understood. We examined this through the lens of endurance running. Previous research concerning endurance running has focused on locomotor energetic economy. We considered a less-studied dimension of functionality, thermoregulation. The performance of male ultra-marathon runners (n = 88) competing in hot and cold environments was analysed with reference to expected thermoregulatory energy costs and the optimal morphologies predicted by Bergmann's and Allen's Rules. Ecogeographical patterning supporting both principles was observed in thermally challenging environments. Finishers of hot-condition events had significantly longer legs than finishers of cold-condition events. Furthermore, hot-condition finishers had significantly longer legs than those failing to complete hot-condition events. A degree of niche-picking was evident; athletes may have tailored their event entry choices in accordance with their previous race experiences. We propose that the interaction between prolonged physical exertion and hot or cold climates may induce powerful selective pressures driving morphological adaptation. The resulting phenotypes reduce thermoregulatory energetic expenditure, allowing diversion of energy to other functional outcomes such as faster running.
Hoy estamos en alborada, es decir, en la hora de preparar a la faena. El éxito depende de la exactitud, de la perfección en cada punto de la obra; y sobre todo de que pongamos al hombre adecuado en el lugar adecuado.
[Today we have reached the dawn, that is, the hour for preparing for the task at hand. Success depends upon the exactitude, upon the perfection of each point within the greater work; and above all that we put the proper man in the proper place.]
José Ortega y Gasset, “Discurso de despedida en la Institución Cultural de Buenos Aires” 1916 (1981: 43)
In 1916, Hipólito Yrigoyen, leader of the Unión Cívica Radical, is elected President of Argentina, thereby giving credence to the possibility of a liberal democratic government after years of oligarchic rule. Argentina also finds itself in the midst of an economic boom that propels the country onto the world stage and coincides with a massive wave of immigration from abroad. Across the Atlantic, Spain finds itself mired in a national crisis after the Desastre del 98 and the loss of its last remaining colonies in the Americas and the Pacific. Despite the fact that Argentina's circumstances appeared to be more favorable than those of its former colonizer at the time, elites and other conservative elements in both countries felt that a political, spiritual, and existential crisis was at hand in the form of the ascent of the modern masses. For the masses personified the threat of anarchic, communistic, and democratic disorder at home and abroad. As a result, these conservative forces combined and conspired in their respective countries and across the Atlantic to restore power to the old guard, or some newfangled version of it, and often did so by any means necessary. Whence the rise of Miguel Primo de Rivera, Francisco Franco, La Falange, and fascism in Spain, which, in certain ways, paralleled the rise of el nacionalismo, José Félix Uriburu, Agustín P. Justo, and the attendant década infame in Argentina.4 Although these reactionary movements included the masses within their respective programs to a certain degree, those in power also ensured that the masses were excluded from power and manipulated from above. Consequently, power was not given over to the many but rather remained in the hands of the few.
To assess differences in cognition functions and gross brain structure in children seven years after an episode of severe acute malnutrition (SAM), compared with other Malawian children.
Design
Prospective longitudinal cohort assessing school grade achieved and results of five computer-based (CANTAB) tests, covering three cognitive domains. A subset underwent brain MRI scans which were reviewed using a standardized checklist of gross abnormalities and compared with a reference population of Malawian children.
Setting
Blantyre, Malawi.
Participants
Children discharged from SAM treatment in 2006 and 2007 (n 320; median age 9·3 years) were compared with controls: siblings closest in age to the SAM survivors and age/sex-matched community children.
Results
SAM survivors were significantly more likely to be in a lower grade at school than controls (adjusted OR = 0·4; 95 % CI 0·3, 0·6; P < 0·0001) and had consistently poorer scores in all CANTAB cognitive tests. Adjusting for HIV and socio-economic status diminished statistically significant differences. There were no significant differences in odds of brain abnormalities and sinusitis between SAM survivors (n 49) and reference children (OR = 1·11; 95 % CI 0·61, 2·03; P = 0·73).
Conclusions
Despite apparent preservation in gross brain structure, persistent impaired school achievement is likely to be detrimental to individual attainment and economic well-being. Understanding the multifactorial causes of lower school achievement is therefore needed to design interventions for SAM survivors to thrive in adulthood. The cognitive and potential economic implications of SAM need further emphasis to better advocate for SAM prevention and early treatment.
Digital literacy has been cited as one of the primary challenges to ensuring data reuse and increasing the value placed on open science. Incorporating published data into classrooms and training is at the core of tackling this issue. This article presents case studies in teaching with different published data platforms, in three different countries (the Netherlands, Canada, and the United States), to students at different levels and with differing skill levels. In outlining their approaches, successes, and failures in teaching with open data, it is argued that collaboration with data publishers is critical to improving data reuse and education. Moreover, increased opportunities for digital skills training and scaffolding across program curriculum are necessary for managing the learning curve and teaching students the values of open science.
The ‘Digital Index of North American Archaeology’ (DINAA) project demonstrates how the aggregation and publication of government-held archaeological data can help to document human activity over millennia and at a continental scale. These data can provide a valuable link between specific categories of information available from publications, museum collections and online databases. Integration improves the discovery and retrieval of records of archaeological research currently held by multiple institutions within different information systems. It also aids in the preservation of those data and makes efforts to archive these research results more resilient to political turmoil. While DINAA focuses on North America, its methods have global applicability.
Horsenettle is a deep-rooted perennial weed that cannot be easily controlled by mechanical means or by a single chemical application. A study was conducted at two sites for two consecutive years to identify biological factors that might limit its growth. Insects, nematodes, and plant pathogens were collected from horsenettle growing in bermudagrass pastures. The insects most commonly found included the Colorado potato beetle and the eggplant flea beetle. An unidentified lepidopteron, family Gelechiidae, was found at very low frequency as pupae in hollow leaf chambers constructed at the apices of flowering meristems. Infested apices bore no fruit. Seven genera of nematodes were found in the soil at both sites, but only very low numbers of lesion nematodes were recovered from horsenettle roots, and these had caused little damage. Root rot was observed under wet soil conditions on plants damaged by trampling. A downy mildew was prevalent at both sites in both years in October.
The effects of bristly starbur interference with peanuts were studied from 1980 through 1983 on a Dothan sandy loam (Plinthic Paleudults). Peanut seed yields, which included kernels plus hulls, were reduced as bristly starbur densities increased from 2 to 64 plants/7.5 m of row. Full-season interference from 8, 16, 32, and 64 bristly starbur plants/7.5 m of row reduced peanut seed yields 14, 26, 43, and 50%, respectively. The seed yield of peanuts maintained weed free for 6 weeks after crop emergence was reduced by no more than 3% compared to peanuts maintained weed free for the entire season. Weed interference for 2 weeks after crop emergence reduced seed yield by an average of 4% over the 3-yr period, based on prediction equations. Bristly starbur interference for 13 weeks after crop emergence reduced peanut forage dry weight yield by 54%. Similarly, peanut interference for 13 weeks after emergence reduced bristly starbur forage dry weight yield by 32%. Bristly starbur density in the forage dry weight studies averaged 35/7.5 m of row. These bristly starbur were confined to a 35-cm band over the drill. Peanut density averaged 72/7.5 m of drill.
Although procedural sedation for cardioversion is a common event in emergency departments (EDs), there is limited evidence surrounding medication choices. We sought to evaluate geographic and temporal variation in sedative choice at multiple Canadian sites, and to estimate the risk of adverse events due to sedative choice.
Methods
This is a secondary analysis of one health records review, the Recent Onset Atrial Fibrillation or Flutter-0 (RAFF-0 [n=420, 2008]) and one prospective cohort study, the Recent Onset Atrial Fibrillation or Flutter-1 (RAFF-1 [n=565, 2010 – 2012]) at eight and six Canadian EDs, respectively. Sedative choices within and among EDs were quantified, and the risk of adverse events was examined with adjusted and unadjusted comparisons of sedative regimes.
Results
In RAFF-0 and RAFF-1, the combination of propofol and fentanyl was most popular (63.8% and 52.7%) followed by propofol alone (27.9% and 37.3%). There were substantially more adverse events in the RAFF-0 data set (13.5%) versus RAFF-1 (3.3%). In both data sets, the combination of propofol/fentanyl was not associated with increased adverse event risk compared to propofol alone.
Conclusion
There is marked variability in procedural sedation medication choice for a direct current cardioversion in Canadian EDs, with increased use of propofol alone as a sedation agent over time. The risk of adverse events from procedural sedation during cardioversion is low but not insignificant. We did not identify an increased risk of adverse events with the addition of fentanyl as an adjunctive analgesic to propofol.
Four soil chronosequences in the southern Great Basin were examined in order to study and quantify soil development during the Quaternary. Soils of all four areas are developed in gravelly alluvial fans in semiarid climates with 8 to 40 cm mean annual precipitation. Lithologies of alluvium are granite-gneiss at Silver Lake, granite and basalt at Cima Volcanic Field, limestone at Kyle Canyon, and siliceous volcanic rocks at Fortymile Wash. Ages of the soils are approximated from several radiometric and experimental techniques, and rates are assessed using a conservative mathematical approach. Average rates for Holocene soils at Silver Lake are about 10 times higher than for Pleistocene soils at Kyle Canyon and Fortymile Wash, based on limited age control. Holocene soils in all four areas appear to develop at similar rates, and Pleistocene soils at Kyle Canyon and Fortymile Wash may differ by only a factor of 2 to 4. Over time spans of several millennia, a preferred model for the age curves is not linear but may be exponential or parabolic, in which rates decrease with increasing age. These preliminary results imply that the geographical variation in rates within the southern Great Basin-Mojave region may be much less significant than temporal variation in rates of soil development. The reasons for temporal variation in rates and processes of soil development are complexly linked to climatic change and related changes in water and dust, erosional history, and internally driven chemical and physical processes.