PHARMACOLOGY & THERAPEUTICS
Utilising Features of Metabolic Syndrome to Cost-Effectively Improve MAFLD Diagnosis Rates in Intelligent Liver Function Testing (iLFT)
Cassandra Baiano | The Universities of St. Andrews & Dundee (ScotGEM)
A novel, algorithm-based testing pathway called “intelligent Liver Function Testing” (iLFT) has been developed in order to facilitate the diagnosis of liver disease. 29.9% of iLFT is returned with descriptive outcomes of elevated ALT alongside other abnormalities, but without a definitive diagnosis. These cases will proceed to costly investigations and lengthy wait times for liver clinic.
Once investigated, 69% of patients with descriptive outcomes will have fatty infiltrates in their liver on ultrasound scan, consistent with Metabolic Associated Fatty Liver Disease (MAFLD), or metabolic associated steatohepatitis (MASH). MAFLD is closely associated with metabolic syndrome and often presents with deranged liver function tests, but requires further investigations. Investigation and treatment is key as MAFLD is one of the leading causes of mortality from liver disease and cancer.
The aim of this study was to cost-effectively improve the iLFT algorithm so that more patients can be confidently assigned a definitive diagnosis of MALFD/MASH instead of a descriptive outcome.
In a binomial logistic regression, BMI and glucose impairment were found to be the strongest predictors of fatty infiltrates in the liver. The iLFT algorithm can be improved to aid the diagnosis of MAFLD by stratifying patients into three BMI categories (≤26, 27-34, ≥35), adding HbA1c, HDL cholesterol, and triglycerides to iLFT panel. This can safely increase the diagnosis rate, reduce referral to ultrasound scan by 18.70%, and reduce referral to liver clinic by 8.22% (95% sensitivity, 95% PPV).
The improvement to the algorithm offers a savings of £18.57 for every £1 spent.
Dipeptidyl Peptidase-IV Inhibitors for Non-Alcoholic Fatty Liver Disease Treatment in Patients with Type 2 Diabetes Mellitus: A Systematic Review
Jessica Quimpo | University of Warwick
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions caused by a build-up of fat in the liver, in the absence of alcohol. It is an important public health concern due to the increasing obesity epidemic. Patients with type 2 diabetes mellitus (T2DM) and NAFLD are at a higher risk of developing severe forms of NAFLD. There is growing evidence for the use of incretin-based therapies, such as dipeptidyl-peptidase-IV inhibitors (DPP-IV inhibitors), to treat the condition. The aim of this review was to determine whether DPP-IV inhibitors are effective in improving NAFLD in T2DM patients.
A systematic review was done and the Jadad scoring system was used to assess the methodological quality of trials.
Only 4 trials fit the inclusion criteria resulting in a total of 168 participants. This review provides further evidence that sitagliptin does not significantly improve hepatic fat content or NAFLD progression according to; histological assessment, MRI imaging and serum ALT levels. The results were limited by a low number of RCTs investigating a wide range of DPP-IV inhibitors, inconsistency between trials, low sample numbers, short duration and a lack of reporting diet and exercise regimes.
Future trials are needed to accurately conclude the efficacy of DPP-IV inhibitors on NAFLD in T2DM patients. These trials should be long in duration and have a large ethnically diverse sample size. Standardisation is required in trials, both in the types of participants included and in the method of measuring drug treatment outcomes.
The Use of Honey in the Prevention and Treatment of Radiation/Chemotherapy-Induced Oral Mucositis in Paediatric Patients
Zohaib Sajid | University of Warwick
Conventional treatment of oral mucositis has been proven to be ineffective and poorly tolerated by paediatric patients, of whom 80% suffer from this debilitating side effect of cancer treatment. Honey has long been known for its antibacterial, anti-inflammatory and wound-healing properties. No review of the evidence for its specific use in paediatric patients has been undertaken, rendering its potential as a gold-standard treatment in children unconfirmed.
Following PRISMA guidelines, four major electronic databases were screened for empirical studies, published from 1st January 2010 to 31st December 2019 in the English language. Any studies featuring only participants outside of an age range of 0-18 years were excluded and the quality of included studies was assessed using Cochrane’s Risk of Bias tool and the Jadad scale. The main investigated outcomes were the impact of honey on mucositis prevention, severity reduction and length of time spent in hospital.
A total of 52 publications were screened from the databases, of which six were included. Three studies were RCTs, with the other three being a quasi-experimental study, observational blind study and open labelled controlled study. The results showed that honey was effective at preventing the development of oral mucositis, reducing the severity of the grade of mucositis and reducing hospitalisation time post-development.
The findings showed that honey is effective in the treatment of oral mucositis in paediatric patients over the age of one year. Due to its sweet nature, ease of availability and cost-effective production, honey would be an easy candidate for widespread implementation to enable patients to benefit from this natural remedy.
Is Sub-Dissociative Ketamine a Safe and Effective Analgesic in Paediatrics for Acute Pain? A Systematic Review and Meta-Analysis
Michael Barrett and Andrea Sargent | University of Warwick
It is widely recognised that pain is undertreated in the paediatric population in an acute setting and the distress caused can lead to long-term detrimental effects. The current recommended treatment for moderate to severe pain in paediatric emergency settings is predominantly opioids, however, an alternative treatment may be beneficial. Sub-dissociative ketamine may improve pain management, by giving a more effective analgesia that can be used for all patients including those with an opioid tolerance. The objectives of this review are two-fold. Firstly, to assess the effectiveness of ketamine in pain reduction compared to current treatments and secondly to evaluate it for safety, by reviewing the adverse event profile.
Searches were conducted using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews to identify randomised controlled trials (RCTs) that compared sub-dissociative ketamine to a control for analgesia in a paediatric population. This review was carried out independently by two researchers (last search conducted in April 2020).
A total of 5 RCTs were used in the meta-analysis which found that ketamine is non-inferior relative to the control group treatments (fentanyl and morphine) for pain management. The standard mean difference (SMD) in pain reduction was -0.06 [95% confidence interval (CI) 0.29, 0.16] at 30-minutes post administration and -0.08 [95% CI -0.33, 0.17] at 60-minutes. However, ketamine was also associated with an increased risk of adverse events, albeit transient and mild, with a risk ratio of 2.94 [CI 95% 1.56, 5.55] compared to the control group.
Sub-dissociative ketamine at a dose of 1mg/kg is an effective analgesia for use in children in an acute setting and is comparable to existing treatments. Ketamine does come with an increased risk of adverse events, although these are transient and mild, therefore unlikely to require medical intervention.
Catching Us When We Fall: A Rapid Evaluation of the Non-Fatal Overdose Response in Dundee, Scotland
Cassandra Baiano | The Universities of St. Andrews & Dundee (ScotGEM)
Opioid-related deaths continue to take the lives of hundreds in Scotland each year, with non-fatal overdose (NFOD) as a significant risk factors for repeat non-fatal and fatal overdoses. Evidence suggests that individuals who survived a recent life-threatening overdose might be more likely to initiate and continue with treatment if they are approached and presented with the right opportunities. In Dundee, Scotland, the Non-Fatal Overdose Response was established in November 2019 to provide an acute, immediate action to those who have experienced an NFOD. The purpose of this evaluation was to evaluate the current Response and examine how this provides the best care arrangements to meet needs.
The reviewers undertook a rapid review of the peer-reviewed literature to identify and assess the feasibility, acceptability, and effectiveness of post-overdose interventions. They also gathered insights from an online survey with 25 key stakeholders and telephone interviews with 12 delivery staff and 5 governance staff. Interviews were transcribed, coded, and analysed using thematic analysis.
The review found that the Response has particular success in its speed, efficiency, effectiveness, coordination and communication, and partnership working. The reviewers have made best-practice recommendations around improving data collection, recording, and sharing; improving measuring, monitoring, and reporting outcomes and feedback; ensuring sustainability, resources, and funding; improving and adding links with other services; promoting a more proactive/preventative approach; and ensuring clear and explicit accountability. Further quantitative and quality improvement research including those who have experienced an NFOD is warranted.