Sedation-Associated Medications at Dementia Diagnosis, Their Receptor Activity, and Associations With Adverse Outcomes in a Large Clinical Cohort.

OBJECTIVES: We aimed to investigate whether sedative medications are associated with adverse outcomes in people with dementia, and whether specific characteristics of these medications predict a higher risk of harm. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 15,210 patients diagnosed with dementia between 2008 and 2017 in South London. METHODS: From recorded medications at dementia diagnosis, we ascertained those with drowsiness listed as a side effect (termed "sedative" hereafter) and subdivided them by frequency and strength of sedation, receptor profile, half-life, and whether they were psychotropics. Multivariable Cox regression models were applied to determine risk of mortality and emergency hospitalization, and generalized estimating equations to investigate cognitive decline. Final models were adjusted for 19 potential confounders, including measures of physical and mental health, functioning, and central anticholinergic burden. RESULTS: At diagnosis, 70.4% of patients with dementia were receiving at least 1 sedative medication. Median survival time was 4.0 years and median time to first hospitalization 1.4 years. After controlling for potential confounders, receipt of any sedative medication at dementia diagnosis was associated with accelerated cognitive decline and a higher hospitalization risk, but only medications with a cautionary warning yielded an increased mortality hazard. Medications acting through γ-aminobutyric acid agonism, psychotropic sedatives, and those with a short half-life were associated with a higher risk of mortality. γ-aminobutyric acid agonists, N-methyl-d-aspartate receptor antagonists, and nonpsychotropic sedatives were associated with an increased hospitalization risk. α1 antagonist, antihistamines, N-methyl-d-aspartate receptor antagonists, psychotropic sedatives, and those with the shortest or longest half-life were associated with accelerated cognitive decline. CONCLUSIONS AND IMPLICATIONS: Receipt of any sedative agent was associated with hospitalization and accelerated cognitive decline. Differences in hazard appear to exist between frequency and strength of sedation, receptor profiles, half-life, and prescribing indication. These differences should be taken into consideration in medication reviews at the time of dementia diagnosis.

Guillain-Barré syndrome following COVID-19: a newly emerging post-infectious complication.

A 57-year-old man presented with a progressive flaccid symmetrical motor and sensory neuropathy following a 1-week history of cough and malaise. He was diagnosed with Guillain-Barré syndrome secondary to COVID-19 and started on intravenous immunoglobulin. He proceeded to have worsening respiratory function and needed intubation and mechanical ventilation. This is the first reported case of this rare neurological complication of COVID-19 in the UK, but it adds to a small but growing body of international evidence to suggest a significant association between these two conditions. Increasing appreciation of this by clinicians will ensure earlier diagnosis, monitoring and treatment of patients presenting with this.

A retrospective notes-based review of patients lost to follow-up from anti-retroviral therapy at Mulanje Mission Hospital, Malawi.

Aim: To analyse patients with HIV who were lost to follow-up from anti-retroviral therapy (ART) at Mulanje Mission Hospital (MMH), Malawi. Methods: All patients on adult antiretroviral combinations at MMH, who were classified as lost to follow-up (LTFU) according to the national guidelines (patients missing a scheduled follow-up visit by more than two months) over a 12-month period, were included in the study and compared against a control group who had never been lost. Variables compared were gender, age, months on ART, time of year, WHO clinical stage, ART regimen, reported side effects, number of doses missed in the previous 12 months, whether the patient has been followed up in the community and if so, the length of time elapsed before follow-up. Results: In all, 136 patients had been LTFU over the previous 12 months at MMH. Of these, 43 had incomplete or missing ART cards, resulting in 93 LTFU patient's data that could be analysed. Patients were more likely to get LTFU if they were men (p=0.03), who had been on anti-retroviral therapy for a short duration (p=0.06) and the proportion of patients who missed more than 4 doses in the previous 12 months was higher among LTFU patients (p=0.05). Only 34.4% of those LTFU had been traced in the community at the time of analysis. Of those traced, 27% had moved to another area, 5.5% had died, 5.5% had the wrong documentation and 62% gave no reason as to why they had missed appointments. Conclusion: This study in MMH has highlighted the importance and feasibility of comprehensive facility-level data-collection, both to identify local patient populations at risk of becoming lost to follow-up and to assess the follow-up measures in place to bring these lost to follow-up patients back into the programme. Even in the short time and with the small sample that was collected, there was evidence that patients most likely to get LTFU in MMH were young men, who had been on anti-retroviral therapy for a short duration and had missed over 4 doses in the last 12 months.