Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study.

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3-13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.

Regional anaesthesia in patients with diabetes.

Diabetes is the most common metabolic condition worldwide and about 20% of surgical patients will have this condition. It is a major risk-factor for worse outcomes after surgery including mortality; infective and non-infective complications; and increased length of stay. However, diabetes is a modifiable risk-factor, and programs to improve medical management have the potential to reduce peri-operative complications and the risk of harm. Regional anaesthesia has well-documented benefits in promoting the restoration of function but there are legitimate concerns that the incidence of complications of regional anaesthesia in patients with diabetes is higher. The aim of this review is to explore in detail the various potential advantages and disadvantages of regional anaesthesia in patients with diabetes. This, in turn, will allow practitioners to undertake more informed shared decision-making and potentially modify their anaesthetic technique for patients with diabetes.

Opioid prescription at postoperative discharge: a retrospective observational cohort study.

Opioid misuse is now considered a major public health epidemic in North America, with substantial social and financial consequences. As well as socio-economic and commercial drivers, modifiable risk-factors that have resulted in this crisis have been identified. The purpose of this study was to identify whether, within England, modifiable drivers for persistent postoperative opioid use were present. This was a retrospective cohort study of practice at 14 National Health Service hospitals across England. Data were collected retrospectively and validated for adult patients undergoing elective intermediate and major or complex major general surgical procedures between 1 and 31 March 2019. Of the 509 patients enrolled from 14 centres, 499 were included in the data analysis. In total, 31.5% (157/499) patients were in the intermediate surgery cohort and 68.5% (342/499) were in the major or complex major surgery cohort, with 21.0% (33/157) and 21.6% (74/342) discharged with opioid medicines to be taken at regular intervals, respectively. There were similar median oral morphine equivalent doses prescribed at discharge. Of patients prescribed regular opioid medicines, 76.6% (82/107) had a specified duration at discharge. However, 72.9% (78/107) had no written deprescribing advice on discharge. Similarly, of patients prescribed 'when required' opioids, 59.6% (93/156) had a specified duration of their prescription and 33.3% (52/156) were given written deprescribing advice. This study has identified a pattern of poor prescribing practices, a lack of guidance and formal training at individual institutions and highlights opportunities for improvement in opioid-prescribing practices within England.

A comparison of postoperative respiratory complications associated with the use of desflurane and sevoflurane: a single-centre cohort study.

Sevoflurane and desflurane are the most commonly used volatile anaesthetics for maintenance of anaesthesia. In this study, we aimed to evaluate the relationship between choice of volatile anaesthetic and early postoperative respiratory complications, and to address a critical knowledge gap in safety outcomes between these two commonly used agents. We performed a retrospective analysis of adult (non-cardiac surgery) patients who received sevoflurane or desflurane for the maintenance of general anaesthesia at our institution between 2005 and 2018. We evaluated the association between desflurane exposure (when compared with sevoflurane) and the primary outcome of postoperative respiratory complications, defined by early post-extubation desaturation (Sp O2  < 90%) or re-intubation within 7 days postoperatively. Multivariable regression analyses were performed and adjusted for confounding factors, including patient, anaesthetic and surgical factors. Propensity matched, interaction and sub-group analyses were performed to assess outcomes in high-risk groups: morbidly obese (BMI > 35 kg.m-2 ); elderly (age > 65 years); and high risk of respiratory complications as well as the primary outcome at 24 h. Desflurane was used for 23,830 patients and sevoflurane for 84,608 patients. Patients exposed to desflurane did not demonstrate a reduced risk of postoperative respiratory complications when compared with sevoflurane (adjusted odds ratio 0.99, 95%CI 0.94-1.04, p = 0.598). These findings were consistent across all sub-groups of high-risk patients and in the propensity score matched cohort. In summary, desflurane use was not associated with reduced postoperative respiratory complications when compared with sevoflurane. In the context of environmental and cost concerns with volatile anaesthetic agents, our study provides important data to support organisational decisions regarding the use of desflurane.

An international multidisciplinary consensus statement on the prevention of opioid-related harm in adult surgical patients.

This international multidisciplinary consensus statement was developed to provide balanced guidance on the safe peri-operative use of opioids in adults. An international panel of healthcare professionals evaluated the literature relating to postoperative opioid-related harm, including persistent postoperative opioid use; opioid-induced ventilatory impairment; non-medical opioid use; opioid diversion and dependence; and driving under the influence of prescription opioids. Recommended strategies to reduce harm include pre-operative assessment of the risk of persistent postoperative opioid use; use of an assessment of patient function rather than unidimensional pain scores alone to guide adequacy of analgesia; avoidance of long-acting (modified-release and transdermal patches) opioid formulations and combination analgesics; limiting the number of tablets prescribed at discharge; providing deprescribing advice; avoidance of automatic prescription refills; safe disposal of unused medicines; reducing the risk of opioid diversion; and better education of healthcare professionals, patients and carers. This consensus statement provides a framework for better prescribing practices that could help reduce the risk of postoperative opioid-related harm in adults.

Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is a hereditary sensory-motor neuropathy characterized by a strong clinical and genetic heterogeneity. Over the past few years, with the occurrence of whole-exome sequencing (WES) or whole-genome sequencing (WGS), the molecular diagnosis rate has been improved by allowing the screening of more than 80 genes at one time. In CMT, except the recurrent PMP22 duplication accounting for about 60% of pathogenic variations, pathogenic copy number variations (CNVs) are rarely reported and only a few studies screening specifically CNVs have been performed. The aim of the present study was to screen for CNVs in the most prevalent genes associated with CMT in a cohort of 200 patients negative for the PMP22 duplication. CNVs were screened using the Exome Depth software on next generation sequencing (NGS) data obtained by targeted capture and sequencing of a panel of 81 CMT associated genes. Deleterious CNVs were identified in four patients (2%), in four genes: GDAP1, LRSAM1, GAN, and FGD4. All CNVs were confirmed by high-resolution oligonucleotide array Comparative Genomic Hybridization (aCGH) and/or quantitative PCR. By identifying four new CNVs in four different genes, we demonstrate that, although they are rare mutational events in CMT, CNVs might contribute significantly to mutational spectrum of Charcot-Marie-Tooth disease and should be searched in routine NGS diagnosis. This strategy increases the molecular diagnosis rate of patients with neuropathy.

Novel CAPN3 variant associated with an autosomal dominant calpainopathy.

AIMS: The most common autosomal recessive limb girdle muscular dystrophy is associated with the CAPN3 gene. The exclusively recessive inheritance of this disorder has been recently challenged by the description of the recurrent variants, c.643_663del21 [p.(Ser215_Gly221del)] and c.598_612del15 [p.(Phe200_Leu204del)], associated with autosomal dominant inheritance. Our objective was to confirm the existence of autosomal dominant calpainopathies. METHODS: Through our activity as one of the reference centres for genetic diagnosis of calpainopathies in France and the resulting collaborations through the French National Network for Rare Neuromuscular Diseases (FILNEMUS), we identified four families harbouring the same CAPN3 heterozygous variant with supposedly autosomal dominant inheritance. RESULTS: We identified a novel dominantly inherited CAPN3 variant, c.1333G>A [p.(Gly445Arg)] in 14 affected patients from four unrelated families. The complementary phenotypic, functional and genetic findings correlate with an autosomal dominant inheritance in these families, emphasizing the existence of this novel transmission mode for calpainopathies. The mild phenotype associated with these autosomal dominant cases widens the phenotypic spectrum of calpainopathies and should therefore be considered in clinical practice. CONCLUSIONS: We confirm the existence of autosomal dominant calpainopathies as an entity beyond the cases related to the in-frame deletions c.643_663del21 and c.598_612del15, with the identification of a novel dominantly inherited and well-documented CAPN3 missense variant, c.1333G>A [p.(Gly445Arg)]. In addition to the consequences for genetic counselling, the confirmation of an autosomal dominant transmission mode for calpainopathies underlines the importance of re-assessing other myopathies for which the inheritance is considered as strictly autosomal recessive.

Pre-operative optimisation of the surgical patient with diagnosed and undiagnosed diabetes: a practical review.

Peri-operative hyperglycaemia, whether the cause is known diabetes, undiagnosed diabetes or stress hyperglycaemia, is a risk factor for harm, increased length of stay and death. There is increasing evidence that peri-operative hyperglycaemia is a modifiable risk factor, and many of the interventions required to improve the outcome of surgery must be instituted before the actual surgical admission. These interventions depend on communication and collaboration within the multidisciplinary team along each stage of the patient journey to ensure that integration of care occurs across the whole of the patient-centred care pathway.

Improving disease knowledge in 6- to 10-year-olds with sickle cell disease: A quasi-experimental study.

BACKGROUND: Increasing knowledge and understanding of disease is known to improve outcomes in persons living with a chronic illness. In this paper, we aim to compare the disease knowledge of children with sickle cell disease (SCD), age 6-10 years, who received an intervention (an educational colouring book on SCD) geared towards improving disease knowledge, to those who did not received the colouring book. METHODS: A quasi-experimental study was conducted where disease knowledge was determined in 56 children who had received the colouring book and compared to 60 children who did not receive this intervention. RESULTS: The mean knowledge score was significantly higher in the intervention group (mean difference = 2.65; 95% CI [1.43, 3.86]), as well as in older children and in those in higher grades but there was no difference between sexes. In a multiple regression model (adjusted R2 : 0.39; p value < .001), knowledge score was significantly higher in those who received the intervention (ß: 2.62; 95% CI [1.48, 3.76]) while adjusting for age, gender, persons living at home, and the father's employment status. CONCLUSION: The study highlights that a simple, inexpensive (cost: US$1/book) child-friendly intervention can significantly improve knowledge about SCD even in young children. It also underlines various social factors that are associated with children's understanding of their disease.