Fatalities associated with gabapentinoids in England (2004-2020).

The gabapentinoids were reclassified as Schedule II medications and Class C drugs in the UK in 2019 due to their potential misuse. In this study we examined deaths following gabapentinoid use in England reported to the National Programme on Substance Abuse Deaths. A total of 3051 deaths were reported (gabapentin: 913 cases; pregabalin: 2322 cases [both detected in 184 cases]). Prescribed and illicitly obtained gabapentinoids accounted for similar proportions of deaths (gabapentin illicit 38.0%, prescribed 37.1%; pregabalin illicit 41.0%, prescribed 34.6%). Opioids were co-detected in most cases (92.0%), and co-prescribed in a quarter (25.3%). Postmortem blood gabapentinoid concentrations were commonly (sub)therapeutic (65.0% of gabapentin cases; 50.8% of pregabalin cases). In only two cases was gabapentinoid toxicity alone attributed in causing death. Gabapentinoids alone rarely cause death. Clinically relevant doses can, however, prove fatal, possibly by reducing tolerance to opioids. Doctors and patients should be aware of this interaction. Gabapentinoid-opioid co-prescribing needs urgent revision.

A deadly trend in fentanyl fatalities (England, 1998-2017).

AIM: To identify trends in drug-related deaths associated with fentanyl and its derivatives, including novel variants, in England, 1998-2017. METHODS: Case reports from the National Programme on Substance Abuse Deaths (NPSAD) where a pharmaceutical fentanyl or non-pharmaceutical fentanyl derivative (NPFD) was found at post-mortem and/or implicated in the death were extracted for analysis. RESULTS: NPSAD has received case reports detailing 298 deaths in England from 1998-2017 where a fentanyl was found at post-mortem and/or implicated in the death. Hospital administered fentanyl is "very safe", whereas pharmaceutical fentanyls in the community, procured either legitimately via prescription or illegitimately, carry high risk of unintentional death. Deaths involving NPFDs, which possess extreme potencies in comparison to morphine, have drastically risen over the past three years, and correlate with an increasing number of available compounds. Males, and those with existing opioid abuse disorders, are particularly susceptible to death related to NPFD intake. CONCLUSIONS: The increasing availability of both pharmaceutical fentanyls and NPFDs represents a serious risk to public health. Unintentional misuse of these compounds in England is contributing to the exponential increase in fentanyl-associated deaths that is being observed at the global scale.

Trends in deaths following drug use in England before, during, and after the COVID-19 lockdowns.

Aim: This research aimed to describe how the characteristics of deaths following drug use changed during the COVID-19 pandemic in England, and how this can inform future strategy to support the health and social care of people who use drugs in future emergency scenarios. Method: All deaths reported to the National Programme on Substance Abuse Deaths which occurred between January 2018 and December 2021 inclusive were extracted for analysis. Exponential smoothing models were constructed to determine any differences between forecasted vs. actual trends. Key results: Following the first lockdown period in England there were significant increases in the proportion of people who died at home beyond the 95% confidence bounds of the exponential smoothing model and concurrent decreases in the proportion of people who died in hospital. Whilst the overall proportion of deaths attributable to opioids did not significantly deviate from the forecasted trend, there were significant increases in methadone-related deaths and decreases in heroin/morphine-related death beyond the 95% confidence bounds. The proportion of deaths concluded as suicide increased, as did those implicating antidepressant use. There were no changes in the proportion of deaths following use of other drug classes, alcohol use in combination with psychoactive drugs, or on decedent demographics (gender, age, and drug user status). A small number of deaths due to drug use had COVID-19 infection itself listed as a cause of death (n = 23). Conclusion: For people who use drugs, the impact of the restrictions due to the COVID-19 pandemic was greater than that of infection from the virus itself. The health and social care strategy for these people needs to be pre-emptively adapted to mitigate against the specific risk factors for fatal drug overdose associated with future emergency scenarios.

Quality of vascular surgery Web sites on the Internet.

INTRODUCTION: This study evaluated the readability, accessibility, usability, and reliability of vascular surgery information on the Internet in the English language. METHODS: The Google, Yahoo, and MSN/Bing search engines were searched for "carotid endarterectomy," "EVAR or endovascular aneurysm repair," and "varicose veins or varicose veins surgery." The first 50 Web sites from each search engine for each topic were analyzed. The Flesch Reading Ease Score and Gunning Fog Index were calculated to assess readability. The LIDA tool (Minervation Ltd, Oxford, UK) was used to assess accessibility, usability, and reliability. RESULTS: The Web sites were difficult to read and comprehend. The mean Flesch Reading Ease scores were 53.53 for carotid endarterectomy, 50.53 for endovascular aneurysm repair, and 58.59 for varicose veins. The mean Gunning Fog Index scores were 12.3 for carotid endarterectomy, 12.12 for endovascular aneurysm repair, and 10.69 for varicose veins. The LIDA values for accessibility were good, but the results for usability and reliability were poor. CONCLUSIONS: Internet information on vascular surgical conditions and procedures is poorly written and unreliable. We suggest that health professionals should recommend Web sites that are easy to read and contain high-quality surgical information. Medical information on the Internet must be readable, accessible, usable, and reliable.

In-Circuit High-Frequency Jet Ventilation for Radiological Tumor Ablation: A Case Series.

High-frequency jet ventilation (HFJV) can reduce organ movement that otherwise complicates percutaneous image-guided ablation (IGA) procedures. This study describes feasibility and safety of the technique in routine use. We describe our method for the use of HFJV and present 169 consecutive cases, including IGA of tumors of the lung, liver, kidney, and pancreas. Intended oncological treatment was delivered in all cases and HFJV used for the duration of treatment in all except one case. We describe the characteristics of patients, procedures, and adverse events. It is feasible to use HFJV as the routine standard of care for IGA.

The effect of telmisartan and ramipril on early morning blood pressure surge: a pooled analysis of two randomized clinical trials.

OBJECTIVES: The period of early morning blood pressure surge is associated with a higher incidence of cardiovascular events than at other times of the day. Antihypertensive medication given once daily in the morning may not protect against this surge if its duration of action is too short. We compared telmisartan, an angiotensin II receptor blocker with a trough-to-peak ratio >90%, with ramipril, an angiotensin-converting enzyme inhibitor with a trough-to-peak ratio of around 50%. METHODS: Data from two prospective, randomized, open-label, blinded endpoint studies comparing telmisartan force titrated to 80 mg once daily and ramipril 10 mg once daily were pooled. Patients had mild-to-moderate hypertension and were assessed using 24-h ambulatory blood pressure monitoring at baseline and endpoint. Early morning blood pressure surge was defined as the difference between mean blood pressure within 2 h after arising and night-time low. Patients were grouped into quartiles according to their baseline systolic surge. RESULTS: Data from 1279 patients were analyzed. Telmisartan changed the overall mean (SE) systolic surge by -1.5 (0.47) mmHg, and ramipril by +0.3 (0.47) mmHg (P=0.0049). The magnitude of surge reduction was greatest in the quartile with highest baseline systolic surge: telmisartan -12.7 (0.91), ramipril -7.8 (1.02) mmHg (P=0.0004). Telmisartan also reduced the surge compared with ramipril in dippers, but there were no differences between the two groups in nondippers. CONCLUSIONS: Telmisartan significantly reduced the early morning systolic blood pressure surge compared with ramipril. A reduction in this surge may help to reduce cardiovascular events in the morning period.

Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability.

EGb 761 is a standardized extract from the Ginkgo biloba leaf and is purported to improve age-related memory impairment. The acute and chronic effect of EGb 761 on synaptic transmission and plasticity in hippocampal slices from young adult (8-12 weeks) and aged (18-24 months) C57Bl/6 mice was tested because hippocampal plasticity is believed to be a key component of memory. Acutely applied EGb 761 significantly increased neuronal excitability in slices from aged mice by reducing the population spike threshold and increased the early phase of long-term potentiation, though there was no effect in slices from young adults. In chronically treated mice fed for 30 days with an EGb 761-supplemented diet, EGb 761 significantly increased the population spike threshold and long-term potentiation in slices from aged animals, but had no effect on slices from young adults. The rapid effects of EGb 761 on plasticity indicate a direct interaction with the glutamatergic system and raise interesting implications with respect to a mechanism explaining its effect on cognitive enhancement in human subjects experiencing dementia.