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Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study

Por: Best · C. S. · Matheson · C. · Robertson · J. · Ritchie · T. · Cowden · F. · Dumbrell · J. · Duncan · C. · Kessavalou · K. · Woolston · C. · Schofield · J.
Objective

To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone.

Design

Population-based cohort study.

Setting

Scotland, UK.

Participants

Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above.

Main outcome measures

All-cause mortality, drug-related deaths and non-drug related deaths.

Secondary outcome

ORT continuous treatment duration.

Analysis

Cox regression with time-varying covariates.

Results

During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30).

Conclusion

Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction.

Trial registration number

NCT04622995.

Reducing the pain of hidradenitis suppurativa wounds

Journal of Wound Care, Volume 33, Issue 1, Page 39-42, January 2024.

Multiocular defect in the Old English Sheepdog: A canine form of Stickler syndrome type II associated with a missense variant in the collagen-type gene <i>COL11A1</i>

by Katherine Stanbury, Renata Stavinohova, Louise Pettitt, Chris Dixon, Ellen C. Schofield, Bryan Mclaughlin, Inka Pettinen, Hannes Lohi, Sally L. Ricketts, James A. Oliver, Cathryn S. Mellersh

Multiocular defect has been described in different canine breeds, including the Old English Sheepdog. Affected dogs typically present with multiple and various ocular abnormalities. We carried out whole genome sequencing on an Old English Sheepdog that had been diagnosed with hereditary cataracts at the age of five and then referred to a board-certified veterinary ophthalmologist due to owner-reported visual deterioration. An ophthalmic assessment revealed that there was bilateral vitreal degeneration, macrophthalmos, and spherophakia in addition to cataracts. Follow-up consultations revealed cataract progression, retinal detachment, uveitis and secondary glaucoma. Whole genome sequence filtered variants private to the case, shared with another Old English Sheepdog genome and predicted to be deleterious were genotyped in an initial cohort of six Old English Sheepdogs (three affected by multiocular defect and three control dogs without evidence of inherited eye disease). Only one of the twenty-two variants segregated correctly with multiocular defect. The variant is a single nucleotide substitution, located in the collagen-type gene COL11A1, c.1775T>C, that causes an amino acid change, p.Phe1592Ser. Genotyping of an additional 14 Old English Sheepdogs affected by multiocular defect revealed a dominant mode of inheritance with four cases heterozygous for the variant. Further genotyping of hereditary cataract-affected Old English Sheepdogs revealed segregation of the variant in eight out of nine dogs. In humans, variants in the COL11A1 gene are associated with Stickler syndrome type II, also dominantly inherited.

Outcomes of first emergency admissions for alcohol-related liver disease in England over a 10-year period: retrospective observational cohort study using linked electronic databases

Por: Bodger · K. · Mair · T. · Schofield · P. · Silberberg · B. · Hood · S. · Fleming · K. M.
Objectives

To examine time trends in patient characteristics, care processes and case fatality of first emergency admission for alcohol-related liver disease (ARLD) in England.

Design

National population-based, retrospective observational cohort study.

Setting

Clinical Practice Research Datalink population of England, 2008/2009 to 2017/2018. First emergency admissions were identified using the Liverpool ARLD algorithm. We applied survival analyses and binary logistic regression to study prognostic trends.

Outcome measures

Patient characteristics; ‘recent’ General Practitioner (GP) consultations and hospital admissions (preceding year); higher level care; deaths in-hospital (including certified cause) and within 365 days. Covariates were age, sex, deprivation status, coding pattern, ARLD stage, non-liver comorbidity, coding for ascites and varices.

Results

17 575 first admissions (mean age: 53 years; 33% women; 32% from most deprived quintile). Almost half had codes suggesting advanced liver disease. In year before admission, only 47% of GP consulters had alcohol-related problems recorded; alcohol-specific diagnostic codes were absent in 24% of recent admission records. Overall, case fatality rate was 15% in-hospital and 34% at 1 year. Case-mix-adjusted odds of in-hospital death reduced by 6% per year (adjusted OR (aOR): 0.94; 95% CI: 0.93 to 0.96) and 4% per year at 365 days (aOR: 0.96; 95% CI: 0.95 to 0.97). Exploratory analyses suggested the possibility of regional inequalities in outcome.

Conclusions

Despite improving prognosis of first admissions, we found missed opportunities for earlier recognition and intervention in primary and secondary care. In 2017/2018, one in seven were still dying during index admission, rising to one-third within a year. Nationwide efforts are needed to promote earlier detection and intervention, and to minimise avoidable mortality after first emergency presentation. Regional variation requires further investigation.

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