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Semaglutide-associated drug-induced liver injury: a case report and review of the literatureSemaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to manage type 2 diabetes and, since 2021, for weight loss in individuals with obesity or weight-related comorbidities. It works by enhancing insulin secretion, delaying gastric emptying and reducing appetite. Common side effects include hypoglycaemia, gastrointestinal disturbances, nausea, weight loss and cholelithiasis. While some studies have noted an association with acute kidney injury, reports of liver injury are rare. We present a rare case of drug-induced liver injury in a middle-aged female, associated with transient liver failure after semaglutide use. She presented one month after starting the medication with rapidly worsening liver function tests. Investigations, including a non-invasive liver screen, viral studies, ultrasound and CT imaging, revealed no clear cause. A liver biopsy supported the diagnosis of drug-induced liver injury. The patient improved with supportive treatment and withdrawal of semaglutide. This case underscores the importance of clinician awareness given its increasing, and often unregulated, use for weight loss.
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A Comparison of the Molecular Pharmacological Properties of Current Short, Long, and Ultra‐Long‐Acting β2‐Agonists Used for Asthma and COPDβ-agonists have been used in asthma for 120 years. There are two recent changes: ultra-long-acting agonists for COPD and new asthma guidelines recommending formoterol/ICS inhalers phasing out short-acting salbutamol inhalers. Few studies directly compare the molecular pharmacological properties of short (salbutamol, terbutaline, fenoterol), long (formoterol, salmeterol), and ultra-long-acting (indacaterol, olodaterol, vilanterol) β2-agonists. Here, the in vitro molecular pharmacological properties of affinity, selectivity, intrinsic efficacy, and duration of β2-agonists at human β2 and β1-adrenoceptors and the 4 β2-polymorphisms stably expressed in CHO cells were directly compared using radioligand binding and functional studies. Whilst short-acting drugs were similar, there was huge variation and complete overlap in the molecular pharmacological properties of drugs labeled as long and ultra-long-acting β2-agonists. Salmeterol and vilanterol were highly β2-selective (> 1000-fold) whereas indacaterol was similar to salbutamol (40-fold). Formoterol and indacaterol were the most efficacious, whereas salmeterol had the longest duration of binding. Salmeterol and vilanterol utilize a β2-specific exosite (β2-H296-K305) for high affinity and selectivity (that does not affect intrinsic efficacy or duration) whilst the β2-selectivity of formoterol and olodaterol resides elsewhere. Duration of binding closely correlated with lipophilicity. β2-polymorphisms had no substantial effect on β2-agonist properties. Comparison with other β-ligands suggests that affinity and duration could both be improved further. However, given the very wide range of molecular pharmacological properties of β-agonists that are clinically effective and widely used, non-pharmacological properties (physiochemical, patient factors, devices and combination inhaler availability) may be as important in final clinical patient outcomes as the molecular pharmacological properties of the individual β2-agonists themselves.
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CASE STUDY: THE USE OF SUBCUTANEOUS CLONIDINE FOR PAIN RELIEF IN COMPLEX CANCER PAIN.Pain is a common symptom in the terminal phase of a cancer patient, and the World Cancer Declaration sets a target for universally available pain control by 2025. Cancer pain can be complex to manage due to the different pathological mechanisms occurring, particularly as it advances and is progressively resisting current analgesia. This case report focuses on the use of clonidine in the palliative care setting, where opioid and non-opioid approaches to analgesia have not controlled the intensifying pain. Sharing this study aims to further the experience base of its utility in complex cancer pain management. The α2A-adrenergic receptor agonist, clonidine, is increasingly being recognised as an effective adjuvant medication for pain and agitation in patients in end-of-life care. This is due to its anti-nociceptive properties and non-opioid action. Evidence of its use in a palliative setting, and relevant pharmacokinetic safety profile, is limited. However, a recent retrospective study in the UK has shown it to be a promising drug due to being well tolerated and its symptomatic benefits. Clonidine was titrated in response to reported and observed pain behaviours, to serve as an adjuvant to opioids. It was noted that there was a significant decrease in opioid usage in correlation with an increased dosage of clonidine. Despite the complicating factor of COVID-19, the patient reported a clinical benefit of clonidine in terms of their pain and comfort. Review of the patient’s integrated Palliative Care Outcome Scale indicated maintained scores with introduction of clonidine compared to prior use of opioids.
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The Association Between Psychosocial Factors and Decision Making Regarding Primary Treatment in Older Women With Early-Stage Breast Cancer.Background: Breast cancer is increasingly prevalent among older adults, who are likely to have numerous comorbidities and unique psychosocial challenges. Aims: The aim of this study was to measure the prevalence of psychosocial factors in a cohort of older women diagnosed with early-stage operable breast cancer and the influence these factors may have on treatment decisions. Methods: As part of a prospective study in three UK centres, 199 patients with a new diagnosis of early-stage operable primary breast cancer, aged ≥ 70 years (mean 77, range 68-93) were recruited. A cancer-specific Comprehensive Geriatric Assessment (CGA) was conducted within 6 weeks of diagnosis. Association between treatment decision and psychosocial aspects (as measured by the 'psychosocial support', 'social activity' and 'social support' domains) of the CGA was determined. Treatment decision was not guided by this study and was determined usual conventional methods as per the breast multi-disciplinary team. Results: Scores for 'psychosocial support' averaged 82.1/102, 'social activity' averaged 13.5/24, and 'social support' averaged 43.3/72; with a higher score indicating a more positive outcome. There was no association between total scores in these domains and the type of treatment received. A lower score in three individual questions was associated with a higher likelihood of non-surgical treatment. Conclusions: While no direct link emerged between overall psychosocial scores and treatment decisions using CGA, specific sub-questions displayed associations with non-surgical treatment. This study is the only one of its kind to our knowledge. This may have implications for the design of a pre-CGA screening tool.
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Intracardiac echocardiography versus transesophageal echocardiography guidance on left atrial appendage occlusion in patients with atrial fibrillation: A systematic review and meta-analysisBackground: Intracardiac echocardiography (ICE) is an innovative technique that has emerged as an alternative to transesophageal echocardiography (TEE) to guide the implantation of a left atrial appendage occlusion (LAAO) device in patients with nonvalvular atrial fibrillation (AF) who cannot tolerate anticoagulants. Purpose: We aim to review the clinical efficacy and safety of ICE compared to TEE to guide the implantation of LAAO devices in patients with AF. Methods: We conducted comprehensive searches across PubMed, CENTRAL, Web of Science, Scopus, and EMBASE until March 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta-analysis was registered with PROSPERO ID: CRD42024542537. Results: We included 19 studies involving 44,706 patients. ICE was associated with a statistically significant high procedure success rate compared to TEE (RR: 1.0055 with 95% CI [1.0006, 1.0104], p = 0.01), but there was no difference in procedure duration (MD: 3.07 with 95% CI [-4.67, 10.80], p = 0.44) between the two groups. However, compared to the ICE group, patients undergoing LAAO under TEE guidance required more than one device more often (RR: 1.39 with 95% CI [1.23, 1.57], p < 0.01). The TEE group also reported a reduced incidence of pericardial effusion compared to the ICE group (RR: 0.65 with 95% CI [0.50, 0.85], p < 0.01). Conclusion: Our meta-analysis concluded that ICE can be a viable alternative to TEE for guiding LAAO, particularly in patients unsuitable for general anesthesia. It can also reduce the need for GA and adverse effects and resources associated with it, require fewer devices, and demonstrate comparable safety and efficacy outcomes, though it may increase the risk of pericardial effusion. Further prospective trials are warranted.
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The Promising Role of Probiotics in the Prevention of Cardiovascular Risk Factors and Their Implication in Reducing Coronary Artery Disease: A Literature Review.Coronary artery disease (CAD) remains one of the most common causes of mortality across the globe, which is strongly associated with modifiable risk factors such as hypertension, hyperlipidemia, type 2 diabetes, and obesity. The role of the gut microbiota in influencing these factors has been established recently. Probiotics, which can modulate gut microbiota, have been investigated as a potential strategy to reduce cardiovascular risk. This review aims to evaluate current evidence on the role of probiotics in reducing CAD risk factors and to explore the mechanisms through which probiotics may support cardiovascular health. This narrative review was conducted using studies published within the last five years. The search included databases such as PubMed, Google Scholar, Medline, and ResearchGate. The selection focused on randomized controlled trials (RCTs), meta-analyses, and reviews that examined the impact of probiotics on CAD and its associated risk factors. Findings from several RCTs and meta-analyses show that probiotic supplementation is associated with improved lipid profiles (including lower LDL-C and triglycerides), better glycemic control, reduced inflammatory markers, and modest reductions in blood pressure and obesity measures. However, results across studies vary due to differences in sample size, duration, probiotic strains, and measured outcomes. Probiotics may offer a beneficial, non-pharmacological option to support conventional CAD therapies, particularly by targeting key modifiable risk factors. While early results are encouraging, further large-scale, long-term studies are necessary to confirm their clinical effectiveness and guide standardized recommendations.
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An Audit Of Oxygen Prescribing Practices In Respiratory Wards Of A Tertiary Care Hospital In Nottinghamshire, Uk.Background: This audit primarily assesses compliance with the British Thoracic Society guidelines (BTS) for oxygen prescriptions in the Respiratory Department at King's Mill Hospital. The results of this audit aim to guide the strategies to improve the oxygen prescription practices in the Trust. Methods: We collected the data on oxygen prescriptions, from the electronic prescribing system, of all the patients admitted in the three respiratory wards of King's Mill Hospital over the period of one week. This data was then recorded and analysed using Audit management and Tracking© (AMAT). Results: The overall compliance score to BTS guidelines for oxygen prescription was 12.2%. Out of the 152 patients, only 8 (5%) had oxygen therapy prescribed and a target oxygen saturation range was identified. No patient had an identifiable oxygen delivery method on their prescription. Conclusions: The current practices of oxygen prescription at the respiratory department of King's Mill Hospital are suboptimal. These findings highlight the risk of serious potential consequences and the opportunity to implement safe prescribing measures for oxygen, like other prescribed medications.
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Retrospective study on pain management pathway for patients with suspected renal/ ureteric colic in a U.K. accidents and emergency department: A quality improvement project.Competing Interests: No competing interests were disclosed. Background: In acute settings around the globe, renal/ureteric colic remains one of the most common diagnoses for patients presenting with loin-to-groin pain. Even though management spans from medical expulsive therapies to surgical options, pain as a significant component of a patient's presentation must be dealt with quickly, decisively, and safely, as it can be excruciating and its effects on overall health are dire. This study aimed to explore compliance with the National Institute for Health and Care Excellence (NICE) guidelines for pain management in patients with suspected renal/ureteric colic. It includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs), intravenous paracetamol, and opioids as first-, second-, and third-line analgesics, respectively, and does not offer antispasmodics. In the event of deviations from the standard, the aim was to put in corrective measures, followed by re-exploration of compliance with patient care. Methods: This study involved a single healthcare facility with the study type being retrospective before interventions and prospective after interventions. In the first cycle, we retrieved and analysed 78 patients records whom had been suspected to have renal/ureteric colic between July and September 2022. The inclusion criteria were documented complaints of "flank/loin-to-groin pain" and diagnosis prior to performing diagnostic tests. We surveyed the first-, second-, and third-line painkillers issued, and whether an antispasmodic was given. We collected and entered data into a Microsoft Excel file and correlated it with NICE standards. Having found deviations from the standard, we conducted interventions, allowed time for clinicians to adapt, and re-explored compliance using patient case records [n=58] between February and May 2023. Results: In the 1 st cycle, 78 patients were suspected of having renal/ureteric colic. M: F = 1.2:1. Non-contrast computerized tomography of the kidney ureters and bladder (NC-CTKUB) confirmed 87% of patients with stones and 3% had no stones. NC-CTKUB was not performed in 9% of patients because they were young, and urinalysis showed no microscopic hematuria. One patient had discharged against medical advise before the NC-CTKUB was performed. Compliance with the NICE pain management guidelines for suspected renal/ureteric colic was full in 23% of cases but unsatisfactory in 78% of cases. In the 2 nd cycle, M: F = 1.5:1, NC-CTKUB was not re-audited, as the first cycle study yielded excellent results, and our action plan resulted in an NICE pain management compliance rate of 56%. Although our interventions resulted in improvements of more than twice the initial results, work still needs to be performed. Conclusion: Clinicians' ability to correctly diagnose renal/ureteric colic is remarkable. However, the pain management compliance rate indicates room for improvement. This may be due to the limited awareness of the NICE guideline or the fact that the clinical team has an affinity for certain analgesics compared to others. We propose the need to consider select variables to existing standard guidelines to enhance compliance for improved patient care. (Copyright: © 2024 Ojo C et al.)
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Worldwide trends in the quality and breadth of clinical investigations of medical devices over the past decade: a scoping review and evidence map.Background Recent regulatory developments in Europe have enhanced the requirements for clinical investigations of medical devices, partly in response to a perceived need for a higher level of evidence that is publicly available. This scoping review aims to map published clinical investigations of medical devices by device type and clinical specialty and summarise key trial design aspects. Methods We developed a search for EMBASE that identified clinical investigations of medical devices during two discrete 3-month periods at the end of 2012 and of 2022. Core information from observational studies was extracted along with details on study design in interventional studies. We developed an evidence map of published studies across device type and clinical specialty and summarised study design aspects. Results We included 682 studies from 2012 and 1682 studies from 2022. Around a quarter of studies were interventional and the remainder being observational and primary outcomes of effectiveness were more common than efficacy. Key study design aspects were frequently unreported, including sample size justification, registration, randomisation technique and funders. Our evidence map demonstrated that predominantly, investigations were of implants and were in a cardiovascular setting. Clinical investigations were broadly similar between 2012 and 2022, though there was a reduction in the proportion of cardiovascular studies, a move in the share of studies coming out of Europe and North America towards Asia and a general improvement in the quality of study design reported. Conclusions Implanted devices in cardiovascular disease and orthopaedics are the focus of a large proportion of published clinical investigations of medical devices. Reporting of key study design aspects of clinical investigations of medical devices are improving but are still below expected requirements.
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Spontaneous Jejunal perforation in coeliac disease: diagnostic dilemma and navigating treatment beyond gluten-free diet in the absence of refractory diseaseCoeliac disease (CD) is relatively common in the West, affecting up to 1% undergoing serological screening and 0.6% histologically confirmed diagnosis of the population [1]. The pathophysiology involves a complex interplay between genetic susceptibility, environmental, and immunologic factors, resulting in chronic inflammation. 95% of people with CD exhibits the HLA-DQ2 and HLA-DQ8 genes which are crucial for presenting gluten-derived peptides to immune cells. The end result is activation of CD4+ T-helper cells in the lamina propria. These cells release inflammatory cytokines such as interferon-gamma that drive chronic inflammation and ultimately villous atrophy [2]. While treatment is mainly conservative and mandatory avoidance of gluten-containing diet, a small proportion fails to response to this measure, leading to progressive disease and refractory malabsorption. This is called the refractory CD (RCD). Diagnosis of this requires absolute proof that Gluten-Free Diet (GFD) has been adopted for at least 12 months, apart from exclusion of other potential causes that may mimic CD [3]. RCD is categorised into type 1 and type 2, based on the presence of aberrant intraepithelial lymphocytes, with the latter carrying a worse prognosis. Most cases of CD associated Ulcerative Jejunitis (UJ), a chronic immune-mediated deep ulceration within the jejunum is found coexisting with type 2 RCD. Very few presents with UJ alone with no RCD association.
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Reviewing the effect of needle size on outcomes of Vacuum-Assisted excision of Breast lesionsWe are writing to highlight methodological concerns regarding the study Effect of Needle Size on Outcomes of Vacuum-Assisted Excision of Breast Lesions, published in the European Journal of Radiology [1]. While the study provides valuable insights into the comparative effectiveness of 7G and 10G needles, certain methodological issues may impact the validity of its conclusions.
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The Role of Combined Renin Angiotensin Aldosterone System Inhibitors RAASi) Plus Beta Blocker Therapy For Cardiotoxicity Prevention In Patients Under Chemotherapy For Breast Cancer: A MetaAnalysis of Randomized Controlled Trials.Introduction: Anti-neoplastic agents, including anthracyclines and trastuzumab, frequently employed in breast cancer treatment carry on considerable cardiotoxic effects impairing both cardiac chamber and cardiac fiber parameters leading to incident heart failure. In response to this challenging side effect, numerous randomized controlled trials (RCTs) have investigated the cardioprotective efficacy of RAASi and beta-blockers (BBs) in patients undergoing anthracycline and trastuzumab chemotherapy. We aim to perform an updated meta-analysis to elucidate the potential cardioprotective properties of these medications in patients undergoing chemotherapy for breast cancer.Methods: A comprehensive search of the literature was performed through April 2024 on PubMed, EMBASE and Clinicaltrials.gov. In total, data from 4 randomized studies were extracted and analyzed. The primary analysis was the effect of RAASi and BBs on LVEF as well as global longitudinal strain (GLS). Data were analyzed using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals for both LVEF and GLS. Data was analyzed using Review Manager 5.3 (RevMan 5.3) software.Results: In total, data from 248 patients (N = 124 on cardioprotection; N = 124 without cardioprotection) undergoing treatment with anti-neoplastic agents for breast cancer were included. At the end of treatment, patients undergoing cardioprotective therapy demonstrated improved LVEF preservation compared to the control group, (mean difference 2.14 [0.03, 4.25]; P=0.05; I2 = 79%). In addition, patients undergoing dual RAASi + BB therapy showed better GLS preservation compared to control group (mean difference –1.37 [-2.01, -0.72]; P < 0.0001; I2 = 0%).Conclusion: In breast cancer patients undergoing anti-neoplastic regimens comprising anthracycline and trastuzumab, the concomitant administration of RAASi and BBs demonstrated better LVEF as well as GLS preservation upon completion of treatment over those without cardioprotective therapy. These findings shed light on the potential benefit derived from the synergistic effects of RAASi and BBs therapy in safeguarding both cardiac chamber and fiber functions amidst aggressive anti-cancer regimens, although further investigations still need to be conducted.
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Flowrna in the Diagnosis of EBV-Related Lymphoproliferative DiseaseEpstein-Barr (EBV) viraemia is frequently encountered in the context of haemophagocytic lymphohistiocytosis (HLH), systemic inflammation and lymphoproliferative disease (LPD). Although EBV typically infects B lymphocytes triggering both polyclonal proliferation and lymphoma, EBV can also infect T and NK cells. Understanding the phenotype of EBV-infected cells can help identify the underlying diagnosis and guide the use of appropriate targeted therapy. We have developed an EBV FlowRNA assay combining the detection of EBV-encoded small RNA (EBER) with multicolour flow cytometry (Collins, Blood, 2020). Here we present a larger case series illustrating how this assay can be used in diagnostic workup.
