Can propensity score matching replace randomized controlled trials?

Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical research.Despite that,various limitations of RCTs prevent its widespread implementation,ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria,amongst others.However,with the introduction of propensity score matching(PSM)as a retrospective statistical tool,new frontiers in establishing causation in clinical research were opened up.PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records,to create a matched sample of participants who received or did not receive the intervention based on their propensity scores,which takes into account characteristics such as age,gender and comorbidities.Given its retrospective nature and its use of observational data from existing sources,PSM circumvents the aforementioned ethical issues faced by RCTs.Majority of RCTs exclude elderly,pregnant women and young children;thus,evidence of therapy efficacy is rarely proven by robust clinical research for this population.On the other hand,by matching study patient characteristics to that of the population of interest,including the elderly,pregnant women and young children,PSM allows for generalization of results to the wider population and hence greatly increases the external validity.Instead of replacing RCTs with PSM,the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other.For example,in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial,the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol.Therefore,PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics,thus providing a fairer comparison for the impact of mannitol.This literature review reports the applications,advantages,and considerations of using PSM with RCTs,illustrating its utility in refining randomization,improving external validity,and accounting for non-compliance to protocol.Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients,while maintaining the robustness of randomization offered by RCTs.

Occam’s razor or Hickam’s dictum-COVID-19 is not a textbook aetiology of acute pancreatitis:A modified Naranjo Score appraisal

BACKGROUND Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe disease.During the coronavirus disease 2019(COVID-19)pandemic,numerous reports of AP have been published,with most authors concluding a causal relationship between COVID-19 and AP.Retrospective case reports or small case series are unable to accurately determine the cause-effect relationship between COVID-19 and AP.AIM To establish whether COVID-19 is a cause of AP using the modified Naranjo scoring system.METHODS A systematic review was conducted on PubMed,World of Science and Embase for articles reporting COVID-19 and AP from inception to August 2021.Exclusion criteria were cases of AP which were not reported to be due to COVID-19 infection,age<18 years old,review articles and retrospective cohort studies.The original 10-item Naranjo scoring system(total score 13)was devised to approximate the likelihood of a clinical presentation to be secondary to an adverse drug reaction.We modified the original scoring system into a 8-item modified Naranjo scoring system(total score 9)to determine the cause-effect relationship between COVID-19 and AP.A cumulative score was decided for each case presented in the included articles.Interpretation of the modified Naranjo scoring system is as follows:≤3:Doubtful,4-6:Possible,≥7:Probable cause.RESULTS The initial search resulted in 909 articles,with 740 articles after removal of duplicates.A total of 67 articles were included in the final analysis,with 76 patients which had AP reported to be due to COVID-19.The mean age was 47.8(range 18-94)years.Majority of patients(73.3%)had≤7 d between onset of COVID-19 infection and diagnosis of AP.There were only 45(59.2%)patients who had adequate investigations to rule out common aetiologies(gallstones,choledocholithiasis,alcohol,hypertriglyceridemia,hypercalcemia and trauma)of AP.Immunoglobulin G4 testing was conducted in 9(13.5%)patients to rule out autoimmune AP.Only 5(6.6%)patients underwent endoscopic ultrasound and/or magnetic resonance cholangiopancreatogram to rule out occult microlithiasis,pancreatic malignancy and pancreas divisum.None of the patients had other recently diagnosed viral infections apart from COVID-19 infection,or underwent genetic testing to rule out hereditary AP.There were 32(42.1%),39(51.3%)and 5(6.6%)patients with doubtful,possible,and probable cause-effect relationship respectively between COVID-19 and AP.CONCLUSION Current evidence is weak to establish a strong link between COVID-19 and AP.Investigations should be performed to rule out other causes of AP before establishing COVID-19 as an aetiology.

Ethical frontiers in liver transplantation

Liver transplantation represents a pivotal intervention in the management of end-stage liver disease,offering a lifeline to countless patients.Despite significant strides in surgical techniques and organ procurement,ethical dilemmas and de-bates continue to underscore this life-saving procedure.Navigating the ethical terrain surrounding this complex procedure is hence paramount.Dissecting the nuances of ethical principles of justice,autonomy and beneficence that underpin transplant protocols worldwide,we explore the modern challenges that plaques the world of liver transplantation.We investigate the ethical dimensions of organ transplantation,focusing on allocation,emerging technologies,and decision-making processes.PubMed,Scopus,Web of Science,Embase and Central were searched from database inception to February 29,2024 using the following key-words:“liver transplant”,“transplantation”,“liver donation”,“liver recipient”,“organ donation”and“ethics”.Information from relevant articles surrounding ethical discussions in the realm of liver transplantation,especially with regards to organ recipients and allocation,organ donation,transplant tourism,new age technologies and developments,were extracted.From the definition of death to the long term follow up of organ recipients,liver transplantation has many ethical quandaries.With new transplant techniques,societal acceptance and perceptions also play a pivotal role.Cultural,religious and regional factors including but not limited to beliefs,wealth and accessibility are extremely influential in public at-titudes towards donation,xenotransplantation,stem cell research,and adopting artificial intelligence.Understanding and addressing these perspectives whilst upholding bioethical principles is essential to ensure just distribution and fair allocation of resources.Robust regulatory oversight for ethical sourcing of organs,ensuring good patient selection and transplant techniques,and high-quality long-term surveillance to mitigate risks is essential.Efforts to promote equitable access to transplantation as well as prioritizing patients with true needs are essential to address disparities.In conclusion,liver transplantation is often the beacon of hope for individuals suffering from end-stage liver disease and improves quality of life.The ethics related to transplantation are complex and multifaceted,considering not just the donor and the recipient,but also the society as a whole.