The Getting It right First Time (GIRFT) programme in urology; rationale and methodology.

The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices.

Occurrence and Severity of Deformational Plagiocephaly in Infants: A Single Center Experience.

OBJECTIVE: To estimate the occurrence and severity of deformational plagiocephaly among infants. METHODS: A hospital-based, cross-sectional study was done in the pediatric ward of a tertiary care hospital between April 1, 2022 to October 31, 2022. Cranial Vault Asymmetry Index (CVAI) and Argenta Clinical Classification were applied to consecutive infants aged 1 month to 1 year till the calculated sample size was achieved. RESULTS: 67 infants were recruited and the occurrence of deformational plagiocephaly in the sample was estimated to be 46.3%. Level 2 severity of deformational plagiocephaly was the commonest, while as per the Argenta classification, majority belonged to type I (39.2%). Male gender and developmental delay were the significant risk factors for plagiocephaly with an odds ratio (95% CI) of 3.73 (1.23, 11.26) and 19.25 (2.31, 160.3), respectively. CONCLUSION: A high occurrence of deformational plagiocephaly was found in infants studied. There is a need for more studies to further corroborate these findings and study its associated factors.

Trapped O2 and the origin of voltage fade in layered Li-rich cathodes.

Oxygen redox cathodes, such as Li1.2Ni0.13Co0.13Mn0.54O2, deliver higher energy densities than those based on transition metal redox alone. However, they commonly exhibit voltage fade, a gradually diminishing discharge voltage on extended cycling. Recent research has shown that, on the first charge, oxidation of O2- ions forms O2 molecules trapped in nano-sized voids within the structure, which can be fully reduced to O2- on the subsequent discharge. Here we show that the loss of O-redox capacity on cycling and therefore voltage fade arises from a combination of a reduction in the reversibility of the O2-/O2 redox process and O2 loss. The closed voids that trap O2 grow on cycling, rendering more of the trapped O2 electrochemically inactive. The size and density of voids leads to cracking of the particles and open voids at the surfaces, releasing O2. Our findings implicate the thermodynamic driving force to form O2 as the root cause of transition metal migration, void formation and consequently voltage fade in Li-rich cathodes.

Endothelial Dysfunction in Children With Nephrotic Syndrome: A Cross-Sectional Study.

Background Children with nephrotic syndrome (NS) have a higher risk of cardiovascular morbidity. Studies on the evaluation of arterial stiffness and endothelial function and its predictive risk factors in these children are limited. Objective The primary objective of the study was to determine arterial stiffness by measuring carotid intimal medial thickness, flow-mediated dilatation, and physiological parameters in children with nephrotic syndrome to predict the risk of premature atherosclerosis as compared to controls. Participants A total number of 33 children with NS in the age group of 2-14 years in remission and 39 healthy controls were enrolled in the study. Out of 33 children with nephrotic syndrome, five were infrequently relapsing NS, eight were frequently relapsing, 16 were steroid dependent, and four were steroid-resistant NS. Intervention Relevant history, physical examination, anthropometric measurements, and laboratory investigations were done. Carotid intimal medial thickness (cIMT), flow-mediated dilatation (FMD), and other physiological parameters were measured in both children with NS and control groups. Outcome Carotid intimal medial thickness (cIMT), flow-mediated dilatation (FMD), and other physiological parameters were compared between children with NS and healthy controls for detecting arterial stiffness and endothelial dysfunction. Results Dyslipidaemia was seen in more than 50% of children during remission. There was neither significant difference in mean cIMT in the common carotid artery nor FMD between the control and study groups. There was a trend of lower Reactive Hyperemia Index (RHI) in children with NS. Conclusion Dyslipidemia persists even during the remission phase in NS. No statistically significant difference is observed in cIMT and percentage proportionate change in FMD in both the study and control groups. Nevertheless, RHI is notably lower in children with NS. These findings need further validation in future studies.

Nivolumab Safety in Renal Cell Carcinoma: A Case Report.

Nivolumab is used to treat several different types of cancers. Although it is generally considered to be effective and well-tolerated, it has been associated with adverse effects requiring discontinuation of treatment, like many other drugs used for cancer. A 70-year-old male was switched from sunitinib to nivolumab for renal cell carcinoma. The patient developed persistent hypothyroidism, onycholysis, and pneumonitis at nivolumab cycle 6, 10, and 11, respectively. Using the Naranjo causality method, the likelihood of causality was deemed "probable" for pneumonitis and hypothyroidism and "possible" for onycholysis. Nivolumab was eventually discontinued due to disease progression, rather than safety concerns. Eudravigilance, the European pharmacovigilance database, was searched for all nivolumab-related individual case safety reports from Malta, up to September 4, 2023. Six reports were identified in Malta, although the 3 events identified in this case report were not reported, suggesting under-reporting in Malta. This case report identified an uncommon nivolumab adverse drug reaction (ADR), onycholysis and showed how, despite the occurrence of 3 ADRs, it was its lack of efficacy rather than its safety which led to its discontinuation in this particular patient.

5% Dextrose in Ringer's Lactate versus 5% Dextrose Normal Saline as Maintenance Intravenous Fluid Therapy in Children - A Randomised Controlled Trial.

OBJECTIVES: To estimate the difference in serum chloride levels between children receiving 5% Dextrose in Ringer's Lactate (RLD5) vs. 5% Dextrose Normal Saline (DNS) and to estimate the incidence of dyselectrolytemia, hyperchloremic metabolic acidosis (HCMA), acute kidney injury (AKI) and all-cause mortality in both groups. METHODS: A randomised controlled trial was conducted in non-critically ill children aged 6 mo to 14 y, admitted between August 2021 and July 2022, requiring intravenous fluids. A sample size of 140 was estimated and randomised, with controls receiving 5% DNS and the intervention group receiving RLD5. Kidney function tests and blood gas analysis were done at admission, 24 h and 48 h after starting the maintenance IV fluid, and outcomes were analysed at 24 h and 48 h. Data was collected using a pre-designed data collection form that included demographic and clinical profile details, and outcomes were analysed using SPSS Version 20 software. RESULTS: Seventy-one children per group were enrolled. The mean chloride difference between the two groups at 24 and 48 h were 1.67 (p-value 0.03) and 2.78 (p-value 0.01), respectively. The incidence of AKI at 24 h and 48 h was 1.4% and 2.8% in the RLD5 group and 0% and 1.4% in the DNS group, respectively. At 24 h and 48 h, 2.8% and 2.8% of children had HCMA in the RLD5 group, and 14% and 4.2% had HCMA in the DNS group, respectively. There was no mortality in either group. CONCLUSIONS: Though clinically insignificant, there was a statistically significant difference in the serum chloride levels between the groups.

Carbon footprint of hospital laundry: a life-cycle assessment.

OBJECTIVES: To assess greenhouse gas (GHG) emissions from a regional hospital laundry unit, and model ways in which these can be reduced. DESIGN: A cradle to grave process-based attributional life-cycle assessment. SETTING: A large hospital laundry unit supplying hospitals in Southwest England. POPULATION: All laundry processed through the unit in 2020-21 and 2021-22 financial years. PRIMARY OUTCOME MEASURE: The mean carbon footprint of processing one laundry item, expressed as in terms of the global warming potential over 100 years, as carbon dioxide equivalents (CO2e). RESULTS: Average annual laundry unit GHG emissions were 2947 t CO2e. Average GHG emissions were 0.225 kg CO2e per item-use and 0.5080 kg CO2e/kg of laundry. Natural gas use contributed 75.7% of on-site GHG emissions. Boiler electrification using national grid electricity for 2020-2022 would have increased GHG emissions by 9.1%, however by 2030 this would reduce annual emissions by 31.9% based on the national grid decarbonisation trend. Per-item transport-related GHG emissions reduce substantially when heavy goods vehicles are filled at ≥50% payload capacity. Single-use laundry item alternatives cause significantly higher per-use GHG emissions, even if reusable laundry were transported long distances and incinerated at the end of its lifetime. CONCLUSIONS: The laundry unit has a large carbon footprint, however the per-item GHG emissions are modest and significantly lower than using single-use alternatives. Future electrification of boilers and optimal delivery vehicle loading can reduce the GHG emissions per laundry item.

How I treat sickle cell disease in pregnancy.

ABSTRACT: Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy's unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.

Trends in day-case bladder outflow obstruction surgery: a study using Hospital Episode Statistics.

OBJECTIVES: To describe the contemporary evolution of day-case bladder outflow obstruction (BOO) surgery in England and to profile day-case BOO surgery practices across England in terms of the types of operation performed and their safety profiles. MATERIALS AND METHODS: This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day-case rate trends were plotted across the study period. Descriptive data, day-case rates and 30-day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day-case surgery was associated with higher 30-day hospital readmissions. RESULTS: Day-case patients were younger, with fewer comorbidities. Time series analysis showed a linear day-case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day-case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day-case rates performed predominantly day-case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day-case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30-day readmission after day-case BOO surgery (all operations pooled), no difference for day-case vs inpatient TURP, and reduced odds following day-case LASER operations. CONCLUSIONS: The day-case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day-case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day-case pathways to treat BOO can be safely developed irrespective of operative modality.

The pharmacological treatment of granulomatosis with polyangiitis: a review of clinical trials registered in clinicaltrials.gov and the International Clinical Trials Registry Platform.

To date, there is no published overview of the drug pipeline in granulomatosis with polyangiitis (GPA), a rare disease. The aim of this study was to identify clinical trials from two study repositories. A review of clinical trials was conducted using publicly available data. Clinicaltrials.gov and International Clinical Trials Registry Platform were searched from inception until 25 September 2022. Only GPA-specific studies were included; these were described in detail. A total of 137 studies were identified in the trial repositories, of which 108 (79%) studies were found to concern GPA. Of these 108 studies, 67 enrolled GPA patients to investigate pharmacotherapy in this disease (62%). Most studies included all severity types (n = 51; 76%); the scope of almost half of the studies was remission induction (n = 33; 49%). The drug class which was by the most widely investigated in trials was the non-corticosteroid immunosuppressant drug class (46; 68.7%), monoclonal antibodies (32; 47.8%), and corticosteroids (31; 46.3%). There is a need for more GPA trials to generate evidence on effectiveness in terms of severity-specificity and maintenance of remission.

The pharmacological treatment of granulomatosis with polyangiitis: a review of clinical trials To date, there is no published overview of the drug pipeline in granulomatosis with polyangiitis (referred to in this paper as GPA), a rare disease. The aim of this study was to identify such studies from two study archives. Clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) were searched from inception until 25th September 2022. Studies recruiting GPA patients were included; these were described in detail. A total of 137 studies were identified in the trial repositories, of which 108 were found to concern GPA. Of these 108 studies, 67 enrolled GPA patients to investigate the treatment of this disease through the administration of drugs. Most studies included all severity types (n = 51); the scope of almost half of the studies was to induce remission (n = 33). The drug classes which were the most widely investigated in trials were non-corticosteroid immunosuppressant drugs (n = 46), monoclonal antibodies (n = 32), and corticosteroids (n = 31). There is a need for more GPA clinical trials to generate evidence on effectiveness of drugs in terms of severity-specificity and maintenance of remission.

Macrolides versus other antibiotics in pediatric scrub typhus: A meta-analysis.

BACKGROUND: While Doxycycline is the recommended drug for treating scrub typhus, there is a growing trend of using Macrolides and Other antibiotics due to their perceived advantages. In this study, we compared the efficacy of Macrolides versus Other antibiotics in the treatment of pediatric scrub typhus. METHODS: Meta-analysis of randomized controlled trials (RCTs) with GRADE (Grading of Recommendations, Assessment, Development and Evaluation) application. Major databases were searched till 30th December 2022. Children of all age groups were included. Primary outcomes included mortality rate and time to defervescence (h). RESULTS: Of the 103 citations retrieved, 5 trials, including 383 children up to 15 years of age with probable and confirmed cases of scrub typhus, were included. None of the trials reported mortality rate. The pooled results from the trials found no significant difference between Azithromycin and Other antibiotics for any of the outcome measures. The certainty of evidence for the primary outcome was deemed to be of "very low certainty", while the certainty of evidence for the secondary outcomes ranged from "low to moderate certainty". CONCLUSIONS: The current meta-analysis revealed that there was no significant difference between Azithromycin and Other antibiotics (such as Doxycycline and Chloramphenicol) in the treatment of scrub typhus in children. However, it's important to note that the evidence generated for the primary outcome was of "very low certainty". PROSPERO REGISTRATION NUMBER: CRD42021276577.

Psychological distress and risk of diabetes among medical students: A cross sectional study.

Background: Medical students are affected both psychologically and physically due to the change in environment for most from home to the hostel and the extensive undergraduate curriculum. This study was undertaken to assess psychological distress and measure surrogate markers of the physical health risk score in a medical college in South India. Methods: The study group included three batches of medical students, from first to third year. Along with anthropometric measurements and a questionnaire on personal history, the Indian Diabetic Risk Score (IDRS), and the Kessler's psychological distress scale based on K10 questions were applied and assessed for each participant. Results: There were gender differences in the association of IDRS with physical activity, Body Mass Index (BMI), Waist Hip Ratio (WHR), and sleep. More than one-third of medical students had various psychological distress grades (40%) and were at risk of developing diabetes (36.7%). There was a significant difference in the K10 scores (p = 0.000) among the three groups, with the first-year students showing maximum psychological distress. Conclusions: A large number of medical students undergo psychological distress and also are at risk for developing Diabetes Mellitus. Long-term cohort studies are needed to assess the effect of such stress on medical students.

An Exploratory Study of the Impact of COVID-19 Vaccine Spontaneous Reporting on Masking Signal Detection in EudraVigilance.

INTRODUCTION: During the signal detection process, statistical methods are used to identify drug-event combinations (DECs) which are disproportionately reported when compared with other drugs and events in the entire database. We hypothesise that the high volume of COVID-19 vaccine adverse drug reaction (ADR) reports transmitted to EudraVigilance may have affected the performance of disproportionality statistics used in routine signal detection, potentially resulting in signals either being masked, or false associations being flagged as potential signals. OBJECTIVE: Our aim was to study the impact of COVID-19 vaccine spontaneous reporting on statistical signal detection in EudraVigilance. METHODS: We recalculated the reporting odds ratio (ROR) for signals that were previously discussed at the level of the Pharmacovigilance Risk Assessment Committee, or signals that were retrieved from EudraVigilance, by omitting COVID-19 vaccine reports from the standard ROR calculation and then comparing the lower confidence interval (LCI) of the recalculated ROR to the LCI of the actual ROR in EudraVigilance. RESULTS: In total, 52 signals for 38 active substances were reviewed. For 35 signals, the LCI of the recalculated ROR value was lower than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had a positive effect on the strength of the signal) while for 15 signals the LCI of the recalculated ROR value was higher than the LCI of the actual ROR (suggesting that COVID-19 vaccine ADR reporting had an attenuating effect on the strength of the signal). For two signals, no change in the ROR was observed. In our analysis, six significant results were found. Five DECs were found to be masked: bleomycin and immune thrombocytopenia (actual ROR LCI = 0.94, recalculated ROR LCI = 1.02), vortioxetine and heavy menstrual bleeding (actual ROR LCI = 0.3, recalculated ROR LCI = 1.06), caplacizumab and heavy menstrual bleeding (actual ROR LCI = 0.98, recalculated ROR LCI = 3.47), ziprasidone and amenorrhoea (actual ROR LCI = 0.84, recalculated ROR LCI = 1.67), and azacitidine and pericarditis (actual ROR LCI = 0.81, recalculated ROR LCI = 2.01). For the DEC of adalimumab and immune reconstitution inflammatory syndrome, the LCI of the actual ROR value was 1.14 and removing COVID-19 vaccine reporting resulted in an LCI of the recalculated ROR value of 0.94 (below threshold). CONCLUSIONS: We demonstrated five cases of masking and one case of false-positive association due to the influence of COVID-19 vaccine spontaneous reporting on the ROR. This suggests that the high number of adverse drug reaction reports for COVID-19 vaccines in EudraVigilance has the potential to affect routine statistical signal detection activities. The impact of COVID-19 vaccine ADR reports on current signal detection practices requires further evaluation and solutions to tackle masking issues in EudraVigilance may need to be developed.

Using telemedicine to improve early medical abortion at home (UTAH): a randomised controlled trial to compare telemedicine with in-person consultation for early medical abortion.

OBJECTIVES: To compare telephone consultations with in-person consultations for the provision of medical abortion (using mifepristone 200 mg and misoprostol 800 µg). We hypothesised that telemedicine consultations would be non-inferior to in-person consultations with a non-inferiority limit of 3%. DESIGN: Randomised controlled trial with 1:1 allocation. SETTING: Community abortion service housed within an integrated sexual and reproductive health service in Edinburgh, UK. PARTICIPANTS: The trial began on 13 January 2020, but was stopped early due to COVID-19; recruitment was suspended on 31 March 2020, and was formally closed on 31 August 2021. A total of 125 participants were randomised, approximately 10% of the total planned, with 63 assigned to telemedicine and 62 to in-person consultation. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: efficacy of medical abortion, defined as complete abortion without surgical intervention. SECONDARY OUTCOMES: satisfaction with consultation type, preparedness, unscheduled contact with care, complication rate, time spent in clinical contact and uptake of long-acting contraception. RESULTS: Primary outcome was available for 115 participants (lost-to-follow-up telemedicine=2, in-person=8), secondary outcomes were available for 110 participants (n=5 and n=10 in telemedicine and in-person groups did not complete questionnaires). There were no significant differences between groups in treatment efficacy (telemedicine 57/63 (90.5%), in-person 48/62 (77.4%)). However, non-inferiority was not demonstrated (+3.3% in favour of telemedicine, CI -6.6% to +13.3%, lower than non-inferiority margin). There were no significant differences in most secondary outcomes, however, there was more unscheduled contact with care in the telemedicine group (12 (19%) vs 3 (5%), p=0.01). The overall time spent in clinical contact was statistically significantly lower in the telemedicine group (mean 94 (SD 24) vs 111 (24) min, p=0.0005). CONCLUSIONS: Telemedicine for medical abortion appeared to be effective, safe and acceptable to women, with less time spent in the clinic. However, due to the small sample size resulting from early cessation, the study was underpowered to confirm this conclusion. These findings warrant further investigation in larger scale studies. TRIAL REGISTRATION NUMBER: NCT04139382.

Clinical, laboratory profile and outcomes in children with snakebite from Eastern India.

Background: Snakebite remains a significant public health problem worldwide, particularly in rural areas with unexpected morbidity and mortality. This study evaluated the clinical, laboratory profile and outcomes in children with snake bites from Eastern India. Methods: This was a retrospective case record-based study between January 2017 and December 2021. The clinical features, complications, laboratory profiles and outcomes were analysed. Results: Thirty children with snake bites were admitted during this study period. There was a male predominance with a ratio of 2.3:1. The mean age of presentation was 10.4 years. About 60% of bites occurred during the rainy season between July and September. Most bites (96%) were on lower limbs, predominantly showing vasculotoxic features followed by neurotoxic and a combined presentation. In this study, around 53% received anti-snake venom (ASV) before reaching our centre; the median time to reach our centre was 13 h. Complications such as acute kidney injury (AKI), cellulitis, shock and coagulation abnormalities were common in those who arrived early (before 6 h) than in those who reached late (after 6 h). Similarly, the mean duration of hospital stay was less for those seeking medical attention early as compared to those reaching late for treatment (4.7 days vs. 7.2 days). Twenty-six out of 30 (86.7%) were discharged without any sequelae, 3 (10%) children were left against medical advice and one died. Conclusions: Snakebite remains a major health problem in children causing significant morbidity and mortality. Children, in general, especially males, are particularly vulnerable because of their playful and explorative nature and considerable time spent in outdoor activities. Preventive measures, education about avoiding traditional first aid methods and early administration of ASV reduce complications, duration of hospital stay and avoid the use of antibiotics.

Mixed-Mode Chromatography and Its Role in Monoclonal Antibody Purification.

As the biopharmaceutical industry matures and embraces process intensification methodologies allied to the emergence of newer personalized medicines, a key constant is the regulatory need to purify products that satisfy the criteria of safety, quality, and efficacy in each batch of released product destined for clinical use. Downstream processing operations and in particular chromatographic separations continue to play a key role in manufacturing strategies with the industry being well served by commercially available resins that provide different options to purify a particular target molecule of interest. In recent years, mixed-mode chromatography, a technique based on multimode interactions between ligands and proteins, had attracted much attention. This short review will discuss the concept and benefit of mixed-mode chromatography in purification strategies and specifically look at its application in the purification of IgG subtype monoclonal antibodies, a key product class in today's industry.

Scale-Up of Protein Purification: Downstream Processing Issues.

Large-scale chromatography operations continue to occupy the central position in the overall strategy for downstream processing and purification of therapeutic protein products for human use. As the biopharmaceutical industry looks forward to embracing new therapeutic modalities such as viral vector-mediated gene therapy, it is becoming evident that chromatographic separations will be also be crucial for success in that discipline. The current industry focus on cell culture intensification strategies that can result in increased process efficiency and lower cost of goods is presenting challenges to the robustness and economics of chromatography processes. To ensure robust and reproducible commercial manufacturing strategies, there is always a mandate to increase the scale of chromatography unit operations that are typically developed and optimized in small-scale development trials. This chapter discusses the key factors in typical chromatography operations that need to be carefully considered and modeled during the process scale-up phase in order to maintain the purity, yield, and quality of a product purified at smaller scales.