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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.
This chapter offers a survey of the principal Merovingian narrative sources. It covers the key chronicles: Gregory, the Chronicles of Fredegar, and the Liber historiae Francorum, plus their relatives. It also offers a guide to the production of hagiography in the period. Throughout the emphasis is on how we might read the stories in these sources, drawing on the competing arguments that have been put forward by scholars about the nature of the texts. Only by understanding some of the strengths and weaknesses of the common approaches to the narrative sources can readers be armed to approach the complexities of Merovingian history.
This chapter provides a survey of ecclesiastical and monastic organisations and how lay people engaged with them. There was no singular ‘Frankish Church’. There was considerable variation in what people wanted, how the liturgy was arranged, access to church councils and books, and how communities connected to Roman, English, Irish, Spanish, or Byzantine religious worlds. Communities were united by relatively compact beliefs, not least the need for imminent moral reform and penance ahead of an inevitable appearance at Judgement Day – whether it was at hand or far in the future.
This chapter analyses the structures of society through the changing faces of estate management, agricultural production, and long-distance trade. It reframes Merovingian society as one radically altered by new landholding patterns, resource utilisation, and tastes in consumption, rather than one trapped passively in post-Roman economic decline. The period still had its challenges, including poverty, pandemic, and environmental change. Our interpretation of the fragmentary and inconsistent evidence very much depends on the areas we choose to prioritise.
This chapter investigates the many faces of cultural production in the Merovingian kingdoms. As this is supposed to be a period of decay, it is crucial to understand the full range of evidence, including the manuscript and associated palaeographical evidence, libraries, the evidence for lay literacy and bureaucratic culture, and the visual and artistic practices that facilitated communication and display. Through these, we can determine that the Merovingian world had its vibrancy and creativity but also that changes in tastes, resources, and organisation meant that much direct evidence has been demonstrably lost.
This chapter examines the period in which the Merovingian kings were allegedly ‘do-nothing kings’. On the whole there was less internecine fighting, but the relative stability was poorly appreciated due to a lack of ‘great’ kings, underwhelming chronicles, and (with hindsight) the rise of the family that would replace the Merovingians as kings in 751. More successful reigns such as those of Dagobert I, Theuderic III, and Childebert III do show attention to law, administration, and aristocratic interests. The fall of the Merovingians may not have seemed inevitable or even desirable until late in the wars of conquest by the Austrasian mayor Charles Martel in the 730s.
This chapter charts the nature of political power from the earliest Merovingian kings to the unification of the kingdoms under Chlothar II in 613. The period witnessed conquest and civil war, as competition for power between kings, queens, and their families transformed late Roman political structures into more fluid and responsive modes of government. It covers the key reigns of Childeric I and Clovis for establishing the power of the Merovingian dynasty through a mixture of war, legend-building, and performance. It also examines how competition between kings in subsequent generations affected how the family was defined, especially under the influence of queens Brunhild and Fredegund.
This chapter introduces how the study of the Merovingian kingdoms has developed since the sixteenth century. Merovingian history is not easily or self-evidently presented in the source material; it has had to be recovered and reconstructed. The historiographical survey is therefore important to understanding how writers and scholars have put that history together. It highlights some of the key political, confessional, theoretical, and methodological issues that have shaped how the period is interpreted, from the Magdeburg Centuriators of the Reformation to the Monumenta Germaniae Historica’s self-consciously ‘scientific’ approach to editing sources.
The final chapter provides an examination of how the Merovingian world was shaped by opposition to paganism, heresy, Judaism, and, at the end, the new Islamic world of the Arab caliphate. The Franks (or at least some of them) had started as pagans themselves in the fifth century, and stories of conversion created important reminders of the journeys to salvation. Whether ‘real paganism’ is easily identifiable in stories or grave goods we may doubt. Similarly, the presence of heresy or Judaism can seem ambiguous when the sources are interrogated. But the creation of Frankish Christianity relied on its contrasts and those fed to it by the Byzantine Empire. Through Merovingian accounts of religious conflict we can discern how the Frankish kingdoms saw their place in the wider world.
This chapter explores how identities were forged and developed under the Merovingians, from the creative fiction of ‘Frankishness’ to more personal identities defined by gender and social status. It examines how identities can appear different through stories, laws, dress, and language, highlighting the importance of how people defined and presented themselves according to need and circumstance. It takes seriously the contention that identity formation fed into discourses of power because they structured hierarchies and issues of inclusion and exclusion.