Forth Valley Royal Hospital

IntroductionFirst-line antibiotics for disease caused by nontuberculous mycobacteria (NTM) are often poorly effective. Bedaquiline is an attractive therapeutic option. Evidence regarding its clinical efficacy is limited. We report outcomes from the largest UK case series of patients with NTM disease who received bedaquiline.MethodsClinicians in NTM centres were contacted to ascertain whether they had used bedaquiline to treat NTM disease. Inclusion criteria for cases were microbiological confirmation of NTM infection and treatment for NTM disease with bedaquiline. Retrospective chart review was undertaken to collate demographics, investigations, regimens and outcomes.ResultsSeventeen patients (10 female; 7 male; median age decile 45–54 years) across 11 hospitals were identified. The commonest pre-existing lung conditions were bronchiectasis (n=5, 29%) and cystic fibrosis (n=4, 24%). Four individuals (24%) had HIV infection; three of whom had AIDS. Nine (53%) had NTM pulmonary disease, three (18%) single-site extrapulmonary disease and five (29%) disseminated disease. NTM disease occurred most frequently secondary to Mycobacterium abscessus (MAB) (n=8, 47%) and Mycobacterium avium complex (MAC) (n=6, 35%).The commonest indication for bedaquiline was NTM treatment failure (n=13, 76%). The BTS MDR TB CAS recommended bedaquiline in seven cases. Bedaquiline was started a median 18.0 (interquartile range (IQR) 4.3–25.5) months after NTM treatment initiation. Median bedaquiline treatment duration was 7.5 (IQR 5.6–12.0) months.Symptoms completely resolved in five (29%) cases, partially resolved in six (35%) and did not change in two (12%). Complete radiological resolution was observed in three (18%), partial resolution in four (24%) and no radiological change in five (29%). Persistent culture conversion was achieved in four (24%) individuals (three MAC, one MAB). Four (24%) individuals (three MAB, one MAC) failed to culture convert.Adverse events associated with bedaquiline included QTc interval prolongation (n=4, 24%), hepatotoxicity (n=3, 18%) and nausea (n=2, 12%). Four individuals (24%) had no bedaquiline-related side effects. Three deaths that occurred while taking bedaquiline were not attributed to the drug by the treating clinicians.ConclusionsAdding bedaquiline to NTM treatment regimens is associated with variable treatment outcomes. Prospective clinical studies evaluating the efficacy of bedaquiline in this context appear warranted.

This network meta-analysis of 13 randomized trials comparing injection treatments for trapeziometacarpal joint arthritis found no robust evidence for any treatment. There is low-quality evidence that corticosteroid and hyaluronic acid injections are superior to placebo for mid-term pain.

Abstract Background Metronidazole, clindamycin, levofloxacin and ciprofloxacin have high oral bioavailability. In many cases, antibiotics are administered IV when the oral route would be appropriate. There are risks of IV administration including complications of IV access and prolonged hospital admission. Objectives To audit current prescribing practices of four antibiotics with high oral bioavailability across medical and surgical wards in Forth Valley Royal Hospital. Methods Patients receiving selected antibiotics were identified using the electronic prescribing system. Patients in intensive care, day units and maternity wards were excluded. An audit tool was used to collect information on antibiotic indication, the ward and specialty, and whether there were any contraindications to oral administration. Contraindications included being nil by mouth, clinically unwell or sepsis, and poor gastrointestinal absorption. Data were collected over a 5 month period. Results In total, 98 IV prescriptions were reviewed. These included metronidazole (87), clindamycin (6) and levofloxacin (5). There were no IV prescriptions of ciprofloxacin. Fifty-three (54%) IV prescriptions were for patients with no contraindication to an oral route. Of these, 37 (70%) were under the care of a surgical specialty and 15 (28%) were under the care of a medical specialty. The most common indication for metronidazole was intra-abdominal infection. A total of 45 of the 87 (52%) patients prescribed IV metronidazole had no contraindication to the oral route and 34 (76%) of these patients were under the care of general surgery. Conclusions High oral bioavailability antibiotics were frequently prescribed IV when the oral route may have been appropriate. Both medical and surgical departments could improve the use of oral antibiotics in appropriate patients. Work is needed to promote awareness among prescribers of these high oral bioavailability antibiotics, particularly the use of oral metronidazole in appropriate surgical patients.

Large clinical trials of intravenous iron for patients with heart failure have studied hospitalized patients immediately prior to discharge (AFFIRM-HF) and outpatients (HEART-FID)1-3; efficacy might differ by enrolment setting. IRONMAN (NCT02642562) was a prospective, randomized, open-label, blinded-endpoint trial comparing intravenous ferric derisomaltose (FDI) with usual care in patients with left ventricular ejection fraction (LVEF) ≤45% and either a serum ferritin <100 μg/L or transferrin saturation (TSAT) <20%.4-6 Patients were grouped according to recruitment settings: (i) hospitalized; (ii) recently hospitalized (within 6 months); and (iii) outpatients without recent hospitalization with elevated plasma concentrations of natriuretic peptides. The primary outcome was heart failure hospitalization (HFH) (recurrent events) or cardiovascular (CV) death. Secondary outcomes included: (i) HFH (first event) or CV death; (ii) CV death; (iii) myocardial infarction, stroke, HFH (first event) or CV death; (iv) all-cause hospitalization; (v) CV hospitalization; (vi) all-cause death; (vii) unplanned hospitalization or all-cause death; and (viii) hospitalization for infection. In this pre-specified subgroup analysis, the effect of FDI on the primary and secondary endpoints compared to usual care was investigated according to enrolment setting. Of 1137 patients randomized, 164 were enrolled in hospital, 208 had been recently hospitalized, and 765 were more stable outpatients. The median follow-up duration was 2.7 years. Patients enrolled in hospital had lowest concentrations of haemoglobin compared to the other groups (median 11.5 vs. 12.0 and 12.3 g/dL), lowest TSAT (medians 10% vs. 14% and 16%), highest proportion with TSAT <20% (90% vs. 76% and 73%), highest ferritin (median 65 vs. 50 and 47 μg/L), lowest estimated glomerular filtration rate (eGFR) (median 45 vs. 48 and 53 mL/min/1.73 m2), lowest systolic blood pressure (median 113 vs. 117 and 121 mmHg), lowest LVEF (median 30% vs. 32% and 35%), were least likely to have ischaemic aetiology (41% vs. 51% and 62%), least likely to have prior acute coronary syndrome (37% vs. 42% and 56%), and had the worst (highest) Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores (physical score median 30 vs. 24 and 22). Other baseline characteristics, including age and sex were similar across groups. Patients enrolled in hospital were more likely on loop diuretics and less likely on renin–angiotensin system inhibitors (angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, sacubitril/valsartan) at baseline. Similar proportions across groups were on beta-blockers, mineralocorticoid receptor antagonists, sodium–glucose cotransporter 2 (SGLT2) inhibitors, and digoxin. Investigators were encouraged to optimize treatment per international clinical practice guidelines at all visits7; therefore, heart failure treatments may have changed over follow-up. Patients enrolled in hospital in the usual care arm had double the rate of primary endpoints compared to outpatients (rate/100 patient-years of 44 in the hospitalized group vs. 22 in the outpatient group). The effect of FDI on the primary and secondary endpoints was similar, in terms of relative risk, irrespective of enrolment setting (Figure 1). The effect of FDI on the change in haemoglobin from baseline to month 4 was consistent across different enrolment settings (pinteraction = 0.16). Enrolment in the outpatient setting was associated with a greater effect of FDI compared to usual care on MLHFQ physical scores at 4 months (difference [95% confidence interval] −3 [−5, −1]) compared to hospitalized (−2 [−6, 2]) and recently hospitalized (2 [−2, 5]) patients (pinteraction = 0.043). IRONMAN is the first heart failure outcome trial to provide within-trial comparisons on the effect of intravenous iron by enrolment setting. As anticipated, patients enrolled in hospital had a higher risk profile compared to outpatients and generally demonstrated higher rates of primary and secondary endpoints. The consistent benefits, in relative terms, between FDI and usual care regardless of whether treatment was initiated in the inpatient or outpatient setting suggest that intravenous iron therapy may be beneficial for a broad range of patients with heart failure throughout their disease trajectory. Hospital admission provides an opportune window for optimizing medical therapy, including correction of iron deficiency. Indeed, if the relative benefits are the same regardless of risk profile, the absolute benefit will be greater amongst patients at higher risk. Compared to those enrolled in outpatient settings, hospitalized patients had features of more severe heart failure (including lower eGFR, systolic blood pressure, and LVEF) which itself may underpin the lower haemoglobin. Haemodilution may also contribute. Lower TSAT, indicating worse iron deficiency, may reflect heart failure severity including inflammation, potentially contributing to hospitalization and lower haemoglobin. Higher ferritin levels seen in hospitalized patients are consistent with greater inflammation due to various causes. In AFFIRM-AHF, intravenous iron was given immediately prior to discharge; in clinical practice it may be challenging to coordinate this. In contrast, in IRONMAN, patients could receive intravenous iron at any time during the inpatient stay, which allows resources to be used more flexibly, helping to mitigate 'therapeutic inertia' and potential delays in treatment initiation. Reassuringly, there was no suggestion of an increased rate of severe infection or an increase in other hazards in patients enrolled in hospital settings. In IRONMAN, there was no difference in the risk of hospitalization due to infection across the three enrolment settings (Figure 1). SGLT2 inhibitors are foundational therapy for heart failure, necessitating understanding their interactions with intravenous iron. In a post-hoc analysis of IRONMAN, there was a trend towards greater increase in haemoglobin with FDI in iron-deficient patients on SGLT2 inhibitors at baseline compared to those not on one.8 This analysis has several limitations that should be acknowledged. The trial was not powered to investigate the effects of treatment in subgroups. Patient characteristics differed in many ways according to recruitment context, which may account for any observed trends or lack thereof. Patients were enrolled solely in the UK, and most were White and men, therefore the results should be extrapolated to other populations with caution. In conclusion, hospitalized patients exhibited a higher rate of the primary outcome compared to outpatients, but the relative risk reduction of FDI was consistent regardless of whether patients were enrolled in hospital wards or outpatient clinics. These findings suggest that intravenous iron therapy may offer benefits across the breadth of clinical settings in the management of heart failure. We thank Public Health Scotland and NHS Digital for the provision of data linkage. We also thank all the participants, physicians, nurses, and other staff who contributed to the IRONMAN study. The study was funded by the British Heart Foundation (grant award CS/15/1/31175) and Pharmacosmos. Pharmacosmos provided supplies of ferric derisomaltose and supported the trial with an additional unrestricted grant. M.C.P. is supported by the British Heart Foundation Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217). Conflict of interest: none declared.

BackgroundEvaluating the impact of simulation-based education (SBE) has prioritised demonstrating a causal link to improved patient outcomes. Recent calls herald a move away from looking for causation to understanding ‘what else happened’. Inspired by Shorrock’s varieties of human work from patient safety literature, this study draws on the concept of work-as-done versus work-as-imagined. Applying this to SBE recognises that some training impacts will be unexpected, and the realities of training will never be quite as imagined. This study takes a critical realist stance to explore the experience and consequences, intended and unintended, of the internal medicine training (IMT) simulation programme in Scotland, to better understand ‘training-as-done’.MethodsCritical realism accepts that there is a reality to uncover but acknowledges that our knowledge of reality is inevitably our construction and cannot be truly objective. The IMT simulation programme involves three courses over a 3-year period: a 3-day boot camp, a skills day and a 2-day registrar-ready course. Following ethical approval, interviews were conducted with trainees who had completed all courses, as well as faculty and stakeholders both immersed in and distant from course delivery. Interviews were audio-recorded, transcribed verbatim and analysed using critical realist analysis, influenced by Shorrock’s proxies for work-as-done.ResultsBetween July and December 2023, 24 interviews were conducted with ten trainees, eight faculty members and six stakeholders. Data described proxies for training-as-done within three broad categories: design, experience and impact. Proxies for training design included training-as-prescribed, training-as-desired and training-as-prioritised which compete to produce training-as-standardised. Experience included training-as-anticipated with pre-simulation anxiety and training-as-unintended with the valued opportunity for social comparison as well as a sense of identity and social cohesion. The impact reached beyond the individual trainee with faculty development and inspiration for other training ventures.ConclusionOur findings highlight unintended consequences of SBE such as social comparison and feeling ‘valued as a trainee, valued as a person’. It sheds light on the fear of simulation, reinforcing the importance of psychological safety. A critical realist approach illuminated the ‘bigger picture’, revealing insights and underlying mechanisms that allow this study to present a new framework for conceptualising training evaluation.

This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.

AimsOccult (clinical) injuries represent 15% of all scaphoid fractures, posing significant challenges to the clinician. MRI has been suggested as the gold standard for diagnosis, but remains expensive, time-consuming, and is in high demand. Conventional management with immobilization and serial radiography typically results in multiple follow-up attendances to clinic, radiation exposure, and delays return to work. Suboptimal management can result in significant disability and, frequently, litigation.MethodsWe present a service evaluation report following the introduction of a quality-improvement themed, streamlined, clinical scaphoid pathway. Patients are offered a removable wrist splint with verbal and written instructions to remove it two weeks following injury, for self-assessment. The persistence of pain is the patient’s guide to ‘opt-in’ and to self-refer for a follow-up appointment with a senior emergency physician. On confirmation of ongoing signs of clinical scaphoid injury, an urgent outpatient ‘fast’-wrist protocol MRI scan is ordered, with instructions to maintain wrist immobilization. Patients with positive scan results are referred for specialist orthopaedic assessment via a virtual fracture clinic.ResultsFrom February 2018 to January 2019, there were 442 patients diagnosed as clinical scaphoid fractures. 122 patients (28%) self-referred back to the emergency department at two weeks. Following clinical review, 53 patients were discharged; MRI was booked for 69 patients (16%). Overall, six patients (< 2% of total; 10% of those scanned) had positive scans for a scaphoid fracture. There were no known missed fractures, long-term non-unions or malunions resulting from this pathway. Costs were saved by avoiding face-to-face clinical review and MRI scanning.ConclusionA patient-focused opt-in approach is safe and effective to managing the suspected occult (clinical) scaphoid fracture.Cite this article: Bone Jt Open 2024;5(2):117–122.

Abstract Background Faecal calprotectin (FCAL) rises rapidly in children with Crohn’s disease (CD) following treatment with exclusive enteral nutrition (EEN). We aimed to identify clinical, dietary and diet-related microbial metabolites which associate with the recurrence of FCAL above 250 mg/kg after 21 days of food reintroduction. Methods Children with CD (age 6-17 years), clinically responding to EEN, were recruited, prospectively, from 11 UK hospitals (January 2020-May 2023, NCT04225689). They provided a single faecal sample before EEN completion (timepoint A) and 6 serial samples (timepoints B-G; 3, 6, 9, 12, 15, 21 days) in the first 21 days of food reintroduction. Faecal short (SCFA) and branched (BCFA) chain fatty acids were measured as proxies of fibre and protein bacterial fermentation, respectively. In faeces, pH, water content (%), Bristol stool score, total microbial load (qPCR) and starch output were measured. Clinical parameters, medications, CRP, ESR, albumin and anthropometry were recorded at EEN completion. Nutrient and food group intake was analysed with Nutritics®. Relationships with FCAL levels were explored. Results Thirty children provided 209/210 (99%) of expected faecal samples. FCAL (median [Q1, Q3], mg/kg) increased within 12 days of food reintroduction (EEN completion: 328 [154, 2370] vs 12 days post-EEN: 1123 (451, 2073), p&amp;lt;0.01) and remained high throughout follow-up. Negative correlations were observed between FCAL with acetate, whereas positive correlations were noted with BCFA (isovalerate and isobutyrate) and their ratio over acetate; the latter remained significant at all 7 timepoints (Figure 1A). Use of immunosuppressants, blood inflammatory markers, clinical and anthropometry at EEN completion were not predictive of FCAL increase post-EEN. In a subset of patients with FCAL&amp;lt;250 mg/kg at EEN completion, (n=13/30), subset regression using ‘end of EEN’ diet-related microbial data, generated a model with 91% accuracy to predict FCAL increase over 250 mg/kg at 21 days of food reintroduction, with isovalerate being the sole predictor of FCAL recurrence (Figure 1B). Average intake of cereal products (median [Q1, Q3], g/day) over 21 days was lower in patients who experienced an FCAL recurrence (FCAL&amp;lt;250mg/kg: 313 (223, 370) vs FCAL&amp;gt;250mg/kg: 186 (167, 217), p=0.013). Positive correlations were observed between the 21-day average intake of cereal products and concentration of SCFA at 21 days post-EEN; acetate (rho=0.38, p=0.041), butyrate (rho=0.46, p=0.0.01) and total SCFA (rho=0.41, p=0.026). Conclusion This study suggests that early FCAL rebound, following treatment with EEN, is related to an increased ratio of dietary protein to fibre bacterial fermentation and a lower intake of cereal products.