Genotype-phenotype of autosomal dominant polycystic kidney disease in Malta.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple renal cysts causing kidney enlargement and end-stage renal disease (ESRD) in half the patients by 60 years of age. The aim of the study was to determine the genetic aetiology in Maltese patients clinically diagnosed with ADPKD and correlate the clinical features. METHODS: A total of 60 patients over 18 years of age clinically diagnosed with ADPKD were studied using a customized panel of genes that had sufficient evidence of disease diagnosis using next generation sequencing (NGS). The genes studied were PKD1, PKD2, GANAB, DNAJB11, PKHD1 and DZIP1L. Selected variants were confirmed by bidirectional Sanger sequencing with specifically designed primers. Cases where no clinically significant variant was identified by the customized gene panel were then studied by Whole Exome Sequencing (WES). Microsatellite analysis was performed to determine the origin of an identified recurrent variant in the PKD2 gene. Clinical features were studied for statistical correlation with genetic results. RESULTS: Genetic diagnosis was reached in 49 (82%) of cases studied. Pathogenic/likely pathogenic variants PKD1 and PKD2 gene were found in 25 and in 23 cases respectively. The relative proportion of genetically diagnosed PKD1:PKD2 cases was 42:38. A pathogenic variant in the GANAB gene was identified in 1 (2%) case. A potentially significant heterozygous likely pathogenic variant was identified in PKHD1 in 1 (2%) case. Potentially significant variants of uncertain significance were seen in 4 (7%) cases of the study cohort. No variants in DNAJB11 and DZIP1L were observed. Whole exome sequencing (WES) added the diagnostic yield by 10% over the gene panel analysis. Overall no clinically significant variant was detected in 6 (10%) cases of the study population by a customized gene panel and WES. One recurrent variant the PKD2 c.709+1G > A was observed in 19 (32%) cases. Microsatellite analysis showed that all variant cases shared the same haplotype indicating that their families may have originated from a common ancestor and confirmed it to be a founder variant in the Maltese population. The rate of decline in eGFR was steeper and progression to ESRD was earlier in cases with PKD1 variants when compared to cases with PKD2 variants. Cases segregating truncating variants in PKD1 showed a significantly earlier onset of ESRD and this was significantly worse in cases with frameshift variants. Overall extrarenal manifestations were commoner in cases segregating truncating variants in PKD1. CONCLUSIONS: This study helps to show that a customized gene panel is the first-line method of choice for studying patients with ADPKD followed by WES which increased the detection of variants present in the PKD1 pseudogene region. A founder variant in the PKD2 gene was identified in our Maltese cohort with ADPKD. Phenotype of patients with ADPKD is significantly related to the genotype confirming the important role of molecular investigations in the diagnosis and prognosis of polycystic kidney disease. Moreover, the findings also highlight the variability in the clinical phenotype and indicate that other factors including epigenetic and environmental maybe be important determinants in Autosomal Dominant Polycystic Kidney Disease.

COVID-19 vaccination attitudes across the European continent.

This study was conducted to determine the predictors of COVID-19 vaccination attitudes across multiple waves in seven countries geographically spread across the European continent, using data from a COVID-19 survey provided by the Massachusetts Institute of Technology COVID-19. Facebook users from across the globe participated in this survey which collected information on their knowledge of COVID-19, attitudes towards risk and available information, and their willingness or lack thereof to take the vaccine. In this secondary data analysis study, neural networks were used with special attention given to the importance of the predictors of COVID-19 vaccination attitudes. Perception of social norms regarding COVID-19 vaccination was found to be the most important predictor of vaccine acceptance. Country of residence and wave of data collection were among the important predictors, with different patterns for each country emerging across different waves. Other strong predictors included attitudes towards masks and mask wearing; attitudes towards the influenza vaccine; distrust in government health authorities and scientists; and level of knowledge of existing treatments for COVID-19. The results of this study can inform effective public health prevention and intervention efforts against infectious diseases.

Knowledge gaps of medical and pharmacy students with respect to performance enhancing drugs in sport: a pilot study.

BACKGROUND: Central to the work of medical and pharmacy practitioners is the provision of pharmaceutical support for patients, who may also be competitive athletes. This study aimed to assess the knowledge gaps of medical and pharmacy students at the University of Malta regarding World Anti-Doping Code and the Prohibited List. METHODS: All medical and pharmacy students studying at the University of Malta were invited to participate in an online questionnaire devised by the research team. This questionnaire assessed knowledge regarding the prohibited status of 19 substances, as well as knowledge regarding therapeutic use exemptions. The questionnaire was prepiloted with local experts in the sports doping field to test face validity, and then tested for content clarity and easy of use by 20 medical and pharmacy students. Total scores were used to compare medical student vs. pharmacy student and athlete vs. non-athlete using the Mann-Whitney U Test. RESULTS: A total of 242 students answered the questionnaire, 58% of which were female. 86% of respondents were medical students. From of the cohort of respondents, 22% identified themselves as athletes as per definition provided in the questionnaire. A number of substances, such as diuretics, morphine, cocaine and ecstasy, were incorrectly classified by the majority of participants. Paracetamol, caffeine, vitamins, NSAIDs, and antihistamines were mostly correctly classified. Pharmacy students had better knowledge when compared to medical students (U value =2734.5, P value =0.034). Student athletes did not have more knowledge than non-athletes (U value =4810.5, P value =0.659). CONCLUSIONS: Medical and Pharmacy students have significant knowledge gaps when it comes to performance enhancing drugs in sport. Sports pharmacy should be included as part of the undergraduate curriculum for both medicine and pharmacy, but especially for medical students who will be future prescribers.

A randomized, controlled trial on the effect of anesthesia on chronic pain after total knee arthroplasty.

Aim: The study sought to evaluate the influence of anesthesia on chronic pain after total knee arthroplasty (TKA). Methods: This was a single-center, randomized controlled study, with patients receiving a spinal anesthetic (SP) alone or a general anesthetic (GA) with femoral block, with follow-up at 3 and at 6 months. The primary outcome was the WOMAC® score at 6 months. Results: 199 patients were enrolled. Group SP had better function (WOMAC: GA: 16.9 vs SP: 14.4, p = 0.015) and less pain (WOMAC pain: GA: 3.04 vs SP: 2.69, p = 0.02) at 3 months, but not at 6 months. Overall, 11% of patients had chronic postsurgical pain (CPSP), with Group GA having a higher incidence of CPSP at 6 months. Neuropathic pain increased during the follow-up and was more common in patients with CPSP. Conclusion: An SP reduces pain and incidence of CPSP after TKA. Clinical Trial Registration: NCT04206046 (ClinicalTrials.gov).

Patients who have knee replacement surgery are at risk of remaining in significant pain even up to one year after surgery. Our study aims to look into the potential of reducing this risk by comparing two common forms of anesthesia. 199 patients were randomized to either have a spinal anesthetic (SP) or a general anesthetic with a femoral nerve block. Patients were then followed-up for 6 months, and then asked to report on a validated functional and pain scoring system (WOMAC^®). Patients who had had an SP had better function and less pain at 3 months after surgery, but not at 6 months. The incidence of chronic pain at six month seems to be less with an SP.

Attitudes of Medical Students in Malta Toward Psychiatry and Mental Illness.

OBJECTIVE: The study aimed to explore the attitudes of medical students in Malta toward psychiatry and mental illness. It looked at the effect of sex, clinical exposure, and experience with mental illness on students' attitudes. METHODS: A questionnaire containing the ATP 30 and MICA-2 scales was distributed to all medical students in Malta in a cross-sectional study. Factor analysis was followed by reliability testing using Cronbach Alpha. Factor scores were achieved using the regression method. The independent sample t test and the Mann-Whitney U test were used to check for relationships between factor scores and variable of interest. Following this, the means and medians of factor scores for each group were calculated and compared. RESULTS: Three hundred ninety-six students (51%) answered the questionnaire. Males had more positive attitudes toward psychiatry as a career choice (p = 0.01) and more positive attitudes toward the importance of psychiatry (p = 0.00). Those with clinical exposure to psychiatry had more negative attitudes toward the efficacy of psychiatry and psychiatrists (p = 0.00). Having experience with mental illness in some form was associated with decreased appeal in psychiatry as a career (p = 0.01 for personal experience, p = 0.01 for relatives, p = 0.00 for friends). CONCLUSIONS: The factor structures obtained using ATP 30 and MICA-2 scales in this study are different from those found in the original literature. Having undergone psychiatry rotations had no significant impact on the attitudes toward psychiatry as a career choice but led to more negative attitudes toward the efficacy of psychiatry and psychiatrists.