Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Sustained clinical knowledge improvements from simulation experiences with Simulation via Instant Messaging-Birmingham Advance.

BACKGROUND: Simulation via Instant Messaging-Birmingham Advance (SIMBA) delivers simulation-based learning through WhatsApp and Zoom, helping to sustain continuing medical education (CME) for postgraduate healthcare professionals otherwise disrupted by the coronavirus (COVID-19) pandemic. This study aimed to assess whether SIMBA helped to improve clinical knowledge and if this improvement in knowledge was sustained over time. METHODS: Two SIMBA sessions-thyroid and pituitary-were conducted in July-August 2020. Each session included simulation of various real-life cases and interactive discussion. Participants' self-reported confidence, acceptance, and knowledge were measured using surveys and multiple-choice questions pre- and post-simulation and in a 6- to 12-week follow-up period. The evaluation surveys were designed using Moore's 7 Levels of CME Outcomes Framework. RESULTS: A total of 116 participants were included in the analysis. Significant improvement was observed in participants' self-reported confidence in approach to simulated cases (thyroid, n = 37, P < .0001; pituitary, n = 79, P < .0001). Significant improvement in clinical knowledge was observed following simulation (thyroid, n = 37, P < .0001; pituitary, n = 79, P < .0001). For both sessions, retention of confidence and knowledge was seen at 6-12 weeks' follow-up. CONCLUSIONS: SIMBA increased participants' clinical knowledge on simulated cases and this improvement was retained up to 6-12 weeks after the session. Further studies are required to explore long-term retention and whether it translates to improved real-world clinical practice.

Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors.

BACKGROUND: Data suggest that immunomodulation induced by DNA hypomethylating agents can sensitize tumors to immune checkpoint inhibitors. We conducted a phase 1 dose-escalation trial (NCT02998567) of guadecitabine and pembrolizumab in patients with advanced solid tumors. We hypothesized that guadecitabine will overcome pembrolizumab resistance. METHODS: Patients received guadecitabine (45 mg/m2 or 30 mg/m2, administered subcutaneously on days 1-4), with pembrolizumab (200 mg administered intravenously starting from cycle 2 onwards) every 3 weeks. Primary endpoints were safety, tolerability and maximum tolerated dose; secondary and exploratory endpoints included objective response rate (ORR), changes in methylome, transcriptome, immune contextures in pre-treatment and on-treatment tumor biopsies. RESULTS: Between January 2017 and January 2020, 34 patients were enrolled. The recommended phase II dose was guadecitabine 30 mg/m2, days 1-4, and pembrolizumab 200 mg on day 1 every 3 weeks. Two dose-limiting toxicities (neutropenia, febrile neutropenia) were reported at guadecitabine 45 mg/m2 with none reported at guadecitabine 30 mg/m2. The most common treatment-related adverse events (TRAEs) were neutropenia (58.8%), fatigue (17.6%), febrile neutropenia (11.8%) and nausea (11.8%). Common, grade 3+ TRAEs were neutropaenia (38.2%) and febrile neutropaenia (11.8%). There were no treatment-related deaths. Overall, 30 patients were evaluable for antitumor activity; ORR was 7% with 37% achieving disease control (progression-free survival) for ≥24 weeks. Of 12 evaluable patients with non-small cell lung cancer, 10 had been previously treated with immune checkpoint inhibitors with 5 (42%) having disease control ≥24 weeks (clinical benefit). Reduction in LINE-1 DNA methylation following treatment in blood (peripheral blood mononuclear cells) and tissue samples was demonstrated and methylation at transcriptional start site and 5' untranslated region gene regions showed enriched negative correlation with gene expression. Increases in intra-tumoural effector T-cells were seen in some responding patients. Patients having clinical benefit had high baseline inflammatory signature on RNAseq analyses. CONCLUSIONS: Guadecitabine in combination with pembrolizumab is tolerable with biological and anticancer activity. Reversal of previous resistance to immune checkpoint inhibitors is demonstrated.

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools.

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures.

Developing a simulation-based learning model for acute medical education during COVID-19 pandemic with Simulation via Instant Messaging - Birmingham Advance (SIMBA).

Simulation-based learning (SBL) is well-established in medical education and has gained popularity, particularly during the COVID-19 pandemic when in-person teaching is infeasible. SBL replicates real-life scenarios and provides a fully immersive yet safe learning environment to develop clinical competency. Simulation via Instant Messaging - Birmingham Advance (SIMBA) is an exemplar of SBL, which we previously showed to be effective in endocrinology and diabetes. Previous studies reported the efficacy of SBL in acute medicine. We studied SIMBA as a learning intervention for healthcare professionals interested in acute medicine and defined our aims using the Kirkpatrick model: (i) develop an SBL tool to improve case management; (ii) evaluate experiences and confidence before and after; and (iii) compare efficacy across training levels.Three sessions were conducted, each representing a PDSA cycle (Plan-Do-Study-Act), consisting of four cases and advertised to healthcare professionals at our hospital and social media. Moderators facilitated progression through 25 min simulations and adopted patient and clinical roles as appropriate. Consultants chaired discussion sessions using relevant guidelines. Presimulation and postsimulation questionnaires evaluated self-reported confidence, feedback and intended changes to clinical practice.Improvements were observed in self-reported confidence managing simulated cases across all sessions. Of participants, 93.3% found SIMBA applicable to clinical practice, while 89.3% and 88.0% felt SIMBA aided personal and professional development, respectively. Interestingly, 68.0% preferred SIMBA to traditional teaching methods. Following participant feedback, more challenging cases were included, and we extended the time for simulation and discussion. The transcripts were amended to facilitate more participant-moderator interaction representing clinical practice. In addition, we refined participant recruitment over the three sessions. In cycle 1, we advertised incentives: participation counted towards teaching requirements, certificates and feedback. To rectify the reduction in participants in cycle 2, we implemented new advertisement methods in cycle 3, including on-site posters, reminder emails and recruitment of the defence deanery cohort.

SIMBA: using Kolb's learning theory in simulation-based learning to improve participants' confidence.

BACKGROUND: Simulation via Instant Messaging- Birmingham Advance (SIMBA) delivers simulation-based learning (SBL) through WhatsApp® and Zoom® based on Kolb's experiential learning theory. This study describes how Kolb's theory was implemented in practice during SIMBA adrenal session. METHODS: SIMBA adrenal session was conducted for healthcare professionals and replicated Kolb's 4-stage cycle: (a) concrete experience-online simulation of real-life clinical scenarios, (b) reflective observation-discussion and Q&A following simulation, (c) abstract conceptualisation-post-session MCQs, and (d) active experimentation-intentions to implement the acquired knowledge in future practice. Participants' self-reported confidence levels for simulated and non-simulated cases pre- and post-SIMBA were analysed using Wilcoxon Signed-Rank test. Key takeaway and feedback were assessed quantitatively and qualitatively in a thematic analysis. RESULTS: Thirty-three participants were included in the analysis. A Wilcoxon signed-rank test showed that the SIMBA session elicited a statistically significant change in participants' self-reported confidence in their approach to Cushing's syndrome (Z = 3.873, p = 0.0001) and adrenocortical carcinoma (Z = 3.970, p < 0.0001). 93.9% (n = 31/33) and 84.8% (n = 28/33) strongly agreed/agreed the topics were applicable to their clinical practice and accommodated their personal learning style, respectively. 81.8% (n = 27/33) reported increase in knowledge on patient management, and 75.8% (n = 25/33) anticipated implementing learning points in their practice. CONCLUSIONS: SIMBA effectively adopts Kolb's theory to provide best possible experience to learners, highlighting the advantages of utilising social media platforms for SBL in medical education. The ability to conduct SIMBA sessions at modest cost internationally paves way to engage more healthcare professionals worldwide.

Incidental finding of lipaemia retinalis on diabetic retinal screening.

SUMMARY: A 37-year-old female of South Asian origin was referred to our diabetes clinic for evaluation of an unusual finding during her retinal screening. Her retinal blood vessels appeared white in contrast to the normal pink-red colour. She had type I hyperlipidaemia, confirmed by genotype, and was recently diagnosed with diabetes, secondary to pancreatic insufficiency, for which she had suboptimal control and multiple hospitalisations with recurrent pancreatitis. On examination, she had multiple naevi on her skin; the rest of the examination was unremarkable. The patient did not report any visual disturbances and had intact visual acuity. Investigations showed raised total cholesterol (12.5 mmol/L) and triglycerides (57.7 mmol/L). Following evaluation, the patient was diagnosed with lipaemia retinalis, secondary to type I hyperlipidaemia. The patient was managed conservatively to reduce the cholesterol and triglyceride burdens. However, therapies with orlistat, statin, fibrates and cholestyramine failed. Only a prudent diet, omega-3 fish oil, medium-chain triglycerides oil and glycaemic control optimised with insulin showed some improvements in her lipid profile. Unfortunately, this led her to becoming fat-soluble vitamin deficient; hence, she was treated with appropriate supplementation. She was also recently started on treatment with volanesorsen. Following this, her lipid parameters improved and lipaemia retinalis resolved. LEARNING POINTS: Lipaemia retinalis is an uncommon incidental finding of type I hyperlipidaemia that may not affect vision. Management of associated dyslipidaemia is challenging with minimal response to conventional treatment. Increased awareness of lipaemia retinalis and specialist management is needed as part of regular patient monitoring and personalised management.

Utility of Simulation via Instant Messaging - Birmingham Advance (SIMBA) in medical education during COVID-19 pandemic.

BACKGROUND: Simulation via Instant Messaging - Birmingham Advance (SIMBA) aimed to improve clinicians' confidence in managing various clinical scenarios during the COVID-19 pandemic. METHODS: Five SIMBA sessions were conducted between May and August 2020. Each session included simulation of scenarios and interactive discussion. Participants' self-reported confidence, acceptance, and relevance of the simulated cases were measured. RESULTS: Significant improvement was observed in participants' self-reported confidence (overall n = 204, p<0.001; adrenal n = 33, p<0.001; thyroid n = 37, p<0.001; pituitary n = 79, p<0.001; inflammatory bowel disease n = 17, p<0.001; acute medicine n = 38, p<0.001). Participants reported improvements in clinical competencies: patient care 52.0% (n = 106/204), professionalism 30.9% (n = 63/204), knowledge on patient management 84.8% (n = 173/204), systems-based practice 48.0% (n = 98/204), practice-based learning 69.6% (n = 142/204) and communication skills 25.5% (n = 52/204). CONCLUSION: SIMBA is a novel pedagogical virtual simulation-based learning model that improves clinicians' confidence in managing conditions across various specialties.

Simulation via instant messaging-Birmingham advance (SIMBA) model helped improve clinicians' confidence to manage cases in diabetes and endocrinology.

BACKGROUND: Simulation-based learning (SBL) has been increasingly used in both undergraduate and postgraduate medical training curricula. The aim of Simulation via Instant Messaging-Birmingham Advance (SIMBA) is to create a simple virtual learning environment to improve trainees' self-reported confidence in diabetes and Endocrinology. METHODS: This study was done as part of the continuous professional development for Health Education England West Midlands speciality trainees in diabetes and Endocrinology. Standardized transcripts of anonymized real-life endocrinology (endocrine session) and diabetes cases (diabetes session) were used in the simulation model. Trainees interacted with moderators through WhatsApp® in this model. All cases were then discussed in detail by a consultant endocrinologist with reference to local, national and international guidelines. Trainee acceptance rate and improvement in their self-reported confidence levels post-simulation were assessed. RESULTS: 70.8% (n = 17/24) and 75% (n = 18/24) strongly agreed the simulation session accommodated their personal learning style and the session was engaging. 66.7% (n = 16/24) strongly felt that the simulation was worth their time. In the endocrine session, there was a significant improvement in trainees' confidence in the management of craniopharyngioma (p = 0.0179) and acromegaly (p = 0.0025). There was a trend towards improved confidence levels to manage Cushing's disease and macroprolactinoma. In diabetes session, there was a significant improvement in trainees' confidence to interpret continuous glucose monitor readings (p = 0.01). There was a trend towards improvement for managing monogenic diabetes, hypoglycaemic unawareness and interpreting Libre readings. Overall, there was a significant improvement in trainees' confidence in managing cases that were discussed post-simulation. CONCLUSION: SIMBA is an effective learning model to improve trainees' confidence to manage various diabetes and endocrine case scenarios. More sessions with a variety of other speciality case scenarios are needed to further assess SIMBA's effectiveness and application in other areas of medical training.

Is immune checkpoint inhibitor-associated diabetes the same as fulminant type 1 diabetes mellitus?

Pembrolizumab is an anti-cancer drug that targets programmed cell death protein-1 (PD-1) receptors on lymphocytes resulting in their activation against tumour cells. PD-1 receptors are also interspersed in endocrine organs and pembrolizumab use has long been associated with hypophysitis and thyroiditis. Since the introduction of immune checkpoint inhibitors (ICI), several cases of fulminant type 1 diabetes mellitus (FT1DM) have been reported. However, it is unclear if FT1DM and ICI-induced diabetes are the same pathology. We review the existing literature of ICI-induced diabetes to investigate its nature and to what extent it represents type 1A diabetes and/or FT1DM (type 1B diabetes) using an example case. Our review showed that ICI-induced diabetes may be a different entity to FT1DM. Furthermore, there is limited evidence for the management of ICI-induced T1DM. Further research into its pathophysiology will improve management and possibly prevent this burdensome complication.

Tunable Aryl Imidazolium Recyclable Ionic Liquid with Dual Brønsted-Lewis Acid as Green Catalyst for Friedel-Crafts Acylation and Thioesterification.

Unique tunable aryl imidazolium ionic liquids successfully catalyzed Friedel-Crafts acylation and thioesterification in sealed tubes. These reactions can form a C-C bond and a C-S bond with high atom economy. Ionic liquids exhibited high activity and catalyzed essential reactions with good to excellent yields while retaining their catalytic activities for recycling.

Crystal structure and biophysical characterisation of Helicobacter pylori phosphopantetheine adenylyltransferase.

Helicobacter pylori is a bacterium that causes chronic active gastritis and peptic ulcers. Drugs targeting H. pylori phosphopantetheine adenylyltransferase (HpPPAT), which is involved in CoA biosynthesis, may be useful. Herein, we report the expression in Escherichia coli and purification of recombinant HpPPAT and describe a crystal structure for an HpPPAT/CoA complex. As is the case for E. coli PPAT (EcPPAT), HpPPAT is hexameric in solution and as a crystal. Each protomer has a well-packed dinucleotide-binding fold in which CoA binds. Structural characterisation demonstrated that CoA derived from the E. coli expression system bound tightly to HpPPAT, presumably to initiate feedback inhibition. However, the interactions between the active-site residues of HpPPAT and CoA are not identical to those of other PPATs. Finally, CoA binding affects HpPPAT thermal denaturation.

Structural and functional comparison of cytokine interleukin-1 beta from chicken and human.

Interleukin-1 beta (IL-1ß) is an important cytokine in the immune system. The properties of avian IL-1ßs are less well understood than the mammalian IL-1ßs, and there is no available structure of avian IL-1ßs in the Protein Data Bank. Here, we report the crystal structures of wild-type and Y157F mutant IL-1ßs from chicken. Both the wild-type and mutant IL-1ßs share a beta-trefoil conformation similar to that of human IL-1ß and also have an internal hydrophobic cavity. However, the cavity sizes clearly differ from that of human IL-1ß due to the packing of hydrophobic residues. Our studies also reveal that the relative thermal stability of IL-1ßs does not correlate with cavity size but rather is dependent on the amino acid residues present around the cavity. This cavity serves as a scaffold for maintaining the structure of the IL-1ß core region but does not have a biological function per se. Moreover, we found that human IL-1ß cannot induce chemokine expression in chicken fibroblasts or elevate plasma cortisol levels in chickens, implying a lack of cross-species bioactivity. Close examination reveals that significant structural and sequence differences occur in the terminal and some loop regions between human and chicken IL-1ßs. These variable regions have been shown to be critical for receptor binding, thus resulting in a lack of species cross-reactivity between human and chicken IL-1ß.

Evaluation of life and death studies course on attitudes toward life and death among nursing students.

The aim of this study was to evaluate attitudes toward life and death among nursing students after attending the life and death studies (LDS) program. Both qualitative and quantitative methods were used to collect data. The pretest-posttest control group design randomly assigned students to an experimental (n = 47) or control group (n = 49). The 13-week course included lectures, video appraisal, games, simulations, films, books, assignments and group sharing. Statistical and content analysis were used to analyze qualitative and quantitative data. The findings showed a significant improvement in perception of the meaningfulness of life in four categories of improvement: expanded viewpoint, sadness about death, treating life sincerely, and instilling hope in life. The qualitative data indicated that a positive change in meaning of life was associated with interaction with others and self-reflection.