A systematic review of randomised controlled trials with adaptive and traditional group sequential designs - applications in cardiovascular clinical trials.

BACKGROUND: Trial design plays a key role in clinical trials. Traditional group sequential design has been used in cardiovascular clinical trials over decades as the trials can potentially be stopped early, therefore, it can reduce pre-planned sample size and trial resources. In contrast, trials with adoptive designs provide greater flexibility and are more efficient due to the ability to modify trial design according to the interim analysis results. In this systematic review, we aim to explore characteristics of adaptive and traditional group sequential trials in practice and to gain an understanding how these trial designs are currently being reported in cardiology. METHODS: PubMed, Embase and Cochrane Central Register of Controlled Trials database were searched from January 1980 to June 2022. Randomised controlled phase 2/3 trials with either adaptive or traditional group sequential design in patients with cardiovascular disease were included. Descriptive statistics were used to present the collected data. RESULTS: Of 456 articles found in the initial search, 56 were identified including 43 (76.8%) trials with traditional group sequential design and 13 (23.2%) with adaptive. Most trials were large, multicentre, led by the USA (50%) and Europe (28.6%), and were funded by companies (78.6%). For trials with group sequential design, frequency of interim analyses was determined mainly by the number of events (47%). 67% of the trials stopped early, in which 14 (32.6%) were due to efficacy, and 5 (11.6%) for futility. The commonly used stopping rule to terminate trials was O'Brien- Fleming-type alpha spending function (10 (23.3%)). For trials with adaptive designs, 54% of the trials stopped early, in which 4 (30.8%) were due to futility, and 2 (15.4%) for efficacy. Sample size re-estimation was commonly used (8 (61.5%)). In 69% of the trials, simulation including Bayesian approach was used to define the statistical stopping rules. The adaptive designs have been increasingly used (from 0 to 1999 to 38.6% after 2015 amongst adaptive trials). 25% of the trials reported "adaptive" in abstract or title of the studies. CONCLUSIONS: The application of adaptive trials is increasingly popular in cardiovascular clinical trials. The reporting of adaptive design needs improving.

Four-factor risk score for the prediction of interstitial lung disease in rheumatoid arthritis.

OBJECTIVE: Interstitial lung disease (ILD) is one of the commonest systemic complications in patients with rheumatoid arthritis (RA) and carries a significant morbidity and mortality burden. We aimed to identify key variables to risk-stratify RA patients in order to identify those at increased risk of developing ILD. We propose a probability score based on the identification of these variables. METHODS: A retrospective, multicentre study using clinical data collected between 2010 and 2020, across 20 centres. RESULTS: A total of 430 RA (210 with ILD confirmed on high-resolution computed tomography (HRCT)) patients were evaluated. We explored several independent variables for the risk of developing ILD in RA and found that the key significant variables were smoking (past or present), older age and positive rheumatoid factor/anti-cyclic citrullinated peptide. Multivariate logistic regression models were used to form a scoring system for categorising patients into high and low risk on a scale of 0-9 points and a cut-off score of 5, based on the area under the receiver operating characteristic curve of 0.76 (CI 95% 0.71-0.82). This yielded a sensitivity of 86% and a specificity of 58%. High-risk patients should be considered for investigation with HRCT and monitored closely. CONCLUSION: We have proposed a new model for identifying RA patients at risk of developing ILD. This approach identified four simple clinical variables: age, anti-cyclic citrullinated peptide antibodies, Rheumatoid factor and smoking, which allowed development of a predictive scoring system for the presence of ILD in patients with RA.

Testing the eligibility of glaucoma patients for potential gene therapy among a clinic population.

PURPOSE: Glaucoma patients who deteriorate despite standard treatment may benefit from novel gene therapies. Key inclusion criteria for a glaucoma gene therapy trial were devised. A retrospective chart review in a glaucoma clinic population was conducted. Feasibility of gene therapy inclusion criteria and factors associated with progression and fast progression < -1 decibels/year (dB/y) were evaluated. METHODS: Three hundred and seventy-four primary open-angle glaucoma patients all of whom had performed at least five Swedish interactive threshold algorithm standard visual fields within a 58-month period. Two definitions were applied to characterize visual field progression rate using Guided Progression Analysis for an individual patient based on A, the eye with the greatest visual field loss, or B, the eye with the most rapid progression rate. RESULTS: Mean rate of visual field progression was -0.50 dB/y (Definition A) and -0.64 dB/y (Definition B). 19.0% (A) and 21.9% (B) of eyes, 71 (A) and 82 (B) eyes, were 'fast progressors' (< -1 dB/y). 37 (A) and 43 (B) eyes met the putative gene therapy inclusion criteria (≥ 50 years; mean deviation ≤ -4 to ≥ -12 or ≤ -20 dB, progression rate between -1 and -4 dB/y). Beta blockers (Odds ratio (OR) with 95% Confidence Intervals (CI): 2.84 (1.39-5.80); p = 0.004) (A), (OR (95%CI): 2.48 (1.30-4.75); p = 0.006) (B) and alpha agonists (OR (95%CI): 2.18 (1.14-4.17); p = 0.02) (A), (OR (95%CI) 2.00 (1.08-3.73); p = 0.028) (B) were significantly associated with fast progression. CONCLUSION: A substantial proportion (10%) of patients in this clinic population would meet recommended gene therapy inclusion criteria.

The effect of digoxin on renal function in patients with heart failure.

INTRODUCTION: Digoxin is used in patients with chronic heart failure (CHF) who remain symptomatic despite optimal medical treatment. Impaired renal function is commonly associated with CHF. We investigated the relation between digoxin use and change in renal function over time in patients with CHF. METHODS: One thousand two hundred forty-one patients with symptoms and signs of CHF (average age 72 years (64% male), and median NTproBNP 1426 ng/l (interquartile range 632-2897) were divided into four groups: never on digoxin (N = 394); digoxin throughout (N = 449); started digoxin at some point after baseline (N = 367); and stopped digoxin at some point after baseline (N = 31). The rate of change of estimated glomerular filtration rate (eGFR) was calculated using linear regression. RESULTS: Patients on digoxin throughout had a significantly greater rate of decline in eGFR per year than patients not on digoxin throughout (mean (± standard deviation); - 5 (14) ml/min/1.73m2 per year v - 2 (11) ml/min/1.73m2 per year, P = 0.02). In those patients who started digoxin during follow up, there was no significant difference in the rate of decline in eGFR before and after starting digoxin. There was no correlation between baseline eGFR (or rate of decline in eGFR) and age, haemoglobin or NTproBNP. Compared to patients taking both angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) and beta-blocker (BB), patients who were not taking an ACEi/ARB or BB had a numerically faster rate of decline in eGFR, although this was not statistically significant. CONCLUSION: The rate of decline in renal function is greater in patients with CHF who are taking digoxin.

Comparative Study on the Outcome of Periorbital Wrinkles Treated with Laser-Assisted Delivery of Vitamin C or Vitamin C Plus Growth Factors: A Randomized, Double-blind, Clinical Trial.

BACKGROUND: Despite promising results, laser-assisted drug delivery (LADD) is not yet considered as standard therapies and published data rely mainly on laboratory tests, animal experiments or cadaver skin. OBJECTIVES: This double-blind, prospective, randomized clinical trial investigates the impact in topical application of vitamin C and a cosmeceutical containing growth factors (GFs) on periorbital wrinkles primarily treated with laser skin resurfacing. MATERIAL AND METHODS: In total, 149 female patients with periorbital wrinkles were consented and randomized into two study groups, R-C (receiving vitamin C only) and R-CGF (receiving vitamin C and a cosmeceutical containing growth factors). The statistical analysis evaluated the efficacy of each treatment regimen using software readouts provided by a three-dimensional stereophotogrammetry system prior to treatment and three months after the procedure. Results were compared to confirm if there was a significant change in the skin roughness and the average depth of the wrinkles between the two groups after treatment. RESULTS: There was a significant reduction in both skin roughness and average depth of the wrinkles in the group treated with vitamin C and growth factors (p <0.01) than those treated with LADD followed by topical application of vitamin C alone. There were no cutaneous reactions or adverse systemic reactions observed in this study related to LADD with vitamin C and GFs. CONCLUSION: Controlled laser application might have a great potential to facilitate the absorption of exogenous macromolecules by the skin. Periorbital wrinkles were reduced in both groups, but LADD using vitamin C and GFs provided significantly better results. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment of Scars with Laser-Assisted Delivery of Growth Factors and Vitamin C: A Comparative, Randomised, Double-blind, Early Clinical Trial.

BACKGROUND: Scarring can jeopardize the final result of plastic surgeries. Deep dermal injuries activate dermal fibroblasts that produce excessive amount of collagen and inflammatory cytokines and growth factors, which contributes to increased fibrous tissue and scarring tissue formation. OBJECTIVES: The aim of this early study, double-blind, prospective, randomised clinical trial was to investigate the use of laser-assisted drug delivery (LADD) for scar improvement to support the establishment of LADD as standard therapy modality and to indicate suitable drugs for dermal administration. MATERIAL AND METHODS: In total, 132 patients seeking scar treatment were consented and randomised. The control group (64 patients) received laser resurfacing immediately followed by skin surface application of Vitamin C and 68 patients received laser treatment followed by skin surface application of a cosmeceutical containing growth factors (GFs) and Vitamin C. Photographs were obtained before and three months after the procedure and submitted to three-dimensional reconstruction by the software Dermapix®. Objective measurements provided by the software were statistically analysed and established the differences in the treatment result between the two groups. RESULTS: There was a significant reduction in scar roughness and volume in both groups (p < 0.01). Mann-Whitney test confirmed that the group treated vitamin C and GFs presented significantly better results than the group treated with vitamin C alone (p < 0.01). CONCLUSION: LADD has proven efficient as scars were reduced in both study groups. Furthermore, the addition of growth factors provided statistically significant better outcomes and resulted in more inconspicuous scars. No adverse reactions were observed. CLINICAL TRIAL REGISTRATION: Plataforma Brasil under the number CAAE: 63710716.2.0000.5664. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

The impact of coronary chronic total occlusion percutaneous coronary intervention upon donor vessel fractional flow reserve and instantaneous wave-free ratio: Implications for physiology-guided PCI in patients with CTO.

OBJECTIVE: To investigate the immediate and short term impact of right coronary artery (RCA) chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) upon collateral donor vessel fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). BACKGROUND: CTO PCI influences collateral donor vessel physiology, making the indication and/or timing of donor vessel revascularization difficult to determine. METHODS: In patients with RCA CTO, FFR, iFR, and collateral function index (FFRcoll ) were measured in LAD and LCx pre-CTO PCI, immediately post and at 4 month follow-up. RESULTS: 34 patients underwent successful PCI. In the predominant donor vessel immediately post PCI, FFR, and FFRcoll did not change (0.76 ± 0.12 to 0.75 ± 0.13, P = 0.267 and 0.31 ± 0.10 vs. 0.34 ± 0.11, P = 0.078), but iFR increased significantly (0.86 ± 0.10 to 0.88 ± 0.10, P = 0.012). At follow-up, there was a significant increase in predominant donor FFR and iFR (0.76 ± 0.12 to 0.79 ± 0.11, P = 0.047 and 0.86 ± 0.10 to 0.90 ± 0.07, P = 0.003), accompanied by a significant reduction in FFRcoll (0.31 ± 0.10 to 0.18 ± 0.07 P < 0.0001). These changes resulted in a reclassification of the predominant donor vessel from ischemic to nonischemic in 18% (FFR) and 25% (iFR) of the cases, respectively. CONCLUSIONS: Successful recanalization of an RCA CTO resulted in a modest but statistically significant increase in the predominant donor vessel immediately post CTO PCI in the case of iFR and at 4-month follow-up for FFR and iFR compared to pre-PCI with a concomitant reduction in collateral function.

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure.

BACKGROUND: Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. METHOD AND RESULTS: Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513-1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. CONCLUSIONS: Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

The obesity paradox in type 2 diabetes mellitus: relationship of body mass index to prognosis: a cohort study.

BACKGROUND: Whether obesity is associated with a better prognosis in patients with type 2 diabetes mellitus is controversial. OBJECTIVE: To investigate the association between body weight and prognosis in a large cohort of patients with type 2 diabetes followed for a prolonged period. DESIGN: Prospective cohort. SETTING: National Health Service, England. PATIENTS: Patients with diabetes. MEASUREMENTS: The relationship between body mass index (BMI) and prognosis in patients with type 2 diabetes without known cardiovascular disease at baseline was investigated. Information on all-cause mortality and cardiovascular morbidity (such as the acute coronary syndrome, cerebrovascular accidents, and heart failure) was collected. Cox regression survival analysis, corrected for potential modifiers, including cardiovascular risk factors and comorbid conditions (such as cancer, chronic kidney disease, and lung disease), was done. RESULTS: 10,568 patients were followed for a median of 10.6 years (interquartile range, 7.8 to 13.4). Median age was 63 years (interquartile range, 55 to 71), and 54% of patients were men. Overweight or obese patients (BMI >25 kg/m²) had a higher rate of cardiac events (such as the acute coronary syndrome and heart failure) than those of normal weight (BMI, 18.5 to 24.9 kg/m²). However, being overweight (BMI, 25 to 29.9 kg/m²) was associated with a lower mortality risk, whereas obese patients (BMI >30 kg/m²) had a mortality risk similar to that of normal-weight persons. Patients with low body weight had the worst prognosis. LIMITATION: Data about cause of death were not available. CONCLUSION: In this cohort, patients with type 2 diabetes who were overweight or obese were more likely to be hospitalized for cardiovascular reasons. Being overweight was associated with a lower mortality risk, but being obese was not. PRIMARY FUNDING SOURCE: National Institute for Health Research and University of Hull.

Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value.

BACKGROUND: Left atrial (LA) volume is an important marker of cardiac dysfunction and cardiovascular outcome in heart failure (HF), but LA function is rarely measured. METHODS: Left atrial emptying function (LAEF), its clinical associations and prognostic value was studied in outpatients referred with suspected HF who were in sinus rhythm and had cardiac magnetic resonance imaging (CMRI). Heart failure was defined as relevant symptoms and signs with either a left ventricular ejection fraction (LVEF) <50% or amino-terminal pro-B-type natriuretic peptide (NTproBNP) >400 pg/mL (or >125 pg/mL if taking loop diuretics). RESULTS: Of 982 patients, 664 fulfilled the HF criteria and were in sinus rhythm. The median (interquartile range, IQR) LAEF was 42 (31-51)% and 55 (48-61)% in patients with and without HF (P < 0.001). Patients with HF in the lowest quartile of LAEF (23%; IQR: 17-28%) had lower LV and right ventricular (RV) EF, and greater LV and RV mass and higher plasma NTproBNP than those in the highest quartile of LAEF (56%; IQR: 53-61%). Log[LAEF] and log[NTproBNP] were inversely correlated (r = -0.410, P < 0.001). During a median follow-up of 883 (IQR: 469-1626) days, 394 (59%) patients with HF died or were admitted with HF and 101 (15%) developed atrial fibrillation (AF). In a multivariable Cox model, increasing LAEF, but not LVEF, was independently associated with survival (HR for 10% change: 0.81 (95%CI: 0.73-0.90), P = <0.001). Increasing age and decreasing LAEF predicted incident AF. CONCLUSIONS: In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction.

Vital D: A modifiable occupational risk factor of UK healthcare workers.

BACKGROUND: The role of Vitamin D in immune function is well reported with a growing evidence base linking low levels to poorer outcomes from infectious disease. Vitamin D deficiency and insufficiency are prevalent worldwide with healthcare workers identified as a known at-risk group. Here we aim to investigate serum Vitamin D levels in a UK population of front line healthcare workers and to promote the occupational risk. METHODS: A cross-sectional study of 639 volunteers was conducted to identify the prevalence of Vitamin D deficiency and insufficiency amongst a population of front-line health care workers in the UK. Participant demographics and co-morbid factors were collected at the time of serum sampling for multivariate analysis. RESULTS: Only 18.8% of the population had a normal vitamin D level greater than or equal to 75nmol/L. This is compared to Public Health England's (PHE) stipulated normal levels of 60% during winter. 81.2% had a level less than 75nmol/L, with 51.2% less than 50nmol/L and 6.6% less than 25nmol/L. For serum levels less than 25nmol/L, Asian ethnicity was more likely to have a vitamin D deficiency than non-asian (OR (95%CI): 3.81 (1.73-8.39), p = 0.001), whereas white ethnicity was less likely to have a vitamin D deficiency compared to non-white (OR (95%CI: 0.43 (0.20-0.83), p = 0.03). Other factors that contributed to a higher likelihood of lower-than-normal levels within this population included male sex, decreased age and not taking supplementation. CONCLUSION: It is concluded that our population of healthcare workers have higher rates of abnormal vitamin D levels in comparison with the general UK population reported prevalence. Furthermore, Asian ethnicity and age 30 years and below are more at risk of vitamin D insufficiency and deficiency. This highlights an occupational risk factor for the healthcare community to consider.

Timing of High-Dose-Rate Brachytherapy With External Beam Radiation Therapy in Patients With Intermediate- and High-Risk Localized Prostate Cancer and Its Effects on Toxicity and Quality of Life: A Randomized Controlled Trial (THEPCA).

PURPOSE: High-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) are effective treatments for prostate cancer but cause genitourinary (GU) and gastrointestinal (GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients. The primary objective was to assess differences, if any, in the incidence of grade (G) 3 or higher GU toxicities from treatment. We also aimed to explore the incidence of G1 to G4 GI toxicities, quality of life (QOL), and patient satisfaction. Suppression of prostate-specific antigen (PSA) and signals for survival differences were also analyzed. METHODS AND MATERIALS: This was a single-center randomized trial in patients with intermediate- and high-risk localized prostate cancer who received HDR-BT before (Arm A) or after (Arm B) EBRT. Toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE). The International Prostate Symptom Score (IPSS) was used to assess lower urinary tract symptoms. The International Index of Erectile Function scale (IIEF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) were used to assess erectile dysfunction and QOL at 0, 3, 9, and 12 months. RESULTS: Fifty patients were recruited to each arm, with 48 and 46 patients completing treatment and follow-up in each arm, 81.5% of whom had high-risk disease. There were no G3 or G4 GU or GI toxicities. G1 urinary frequency was the most common adverse event experienced in both arms, peaking in incidence 3 months after treatment commenced (45.7% and 42.2% in Arm A and B, respectively). Up to 11% of patients reported G1 urinary frequency at 12 months. Other G1 GU toxicities experienced by >10% of patients were urinary tract obstruction, tract pain, and urgency. These symptoms also peaked in incidence at 3 months. G2 GU toxicities were uncommon and experienced in a maximum of 2 patients within each arm at any time point. Over 30% of patients had G1 flatulence at baseline, and this remained the most frequently occurring G1 GI toxicity throughout the study, peaking at 12 months (21.4% and 25.6% in Arm A and B, respectively). Other GI toxicities experienced by more than 10% of patients were GI pain, proctitis, and rectal mucositis, most of which demonstrated a peak incidence at 3 or 9 months. G2 GI toxicities were uncommon except for G2 flatulence. No significant difference was found in CTCAE, IPSS, IIEF, FACT-P, and QOL scores between the arms. Median prostate-specific antigen (PSA) follow-up was 5 years. Seven patients had treatment failure in each arm. Disease Free Survival (DFS) was 93.3% and 90.7% at 5 years in Arm A and B, respectively, with median failure time of 60 and 48 months in Arm A and B, respectively. There were no statistically significant differences between arms. CONCLUSIONS: The sequencing of HDR-BT and EBRT did not affect the incidence of G3 or G4 toxicities, and no significant differences were seen in other patient-reported outcomes. Treatment was well tolerated with maintained QOL scores. Treatment failure was low in both arms in a high-risk cohort; however, a larger study with longer follow-up is underway to establish whether the difference in median time to failure between the 2 arms is a signal of superiority.

Health-related quality of life after 12 months post discharge in patients hospitalised with COVID-19-related severe acute respiratory infection (SARI): a prospective analysis of SF-36 data and correlation with retrospective admission data on age, disease severity, and frailty.

Long-term outcome and 'health-related quality of life' (HRQoL) following hospitalisation for COVID-19-related severe acute respiratory infection (SARI) is limited. OBJECTIVE: To assess the impact of HRQoL in patients hospitalised with COVID-19-related SARI at 1 year post discharge, focusing on the potential impact of age, frailty, and disease severity. METHOD: Routinely collected outcome data on 1207 patients admitted with confirmed COVID-19 related SARI across all three secondary care sites in our NHS trust over 3 months were assessed in this retrospective cohort study. Of those surviving 1 year, we prospectively collected 36-item short form (SF-36) HRQoL questionnaires, comparing three age groups (<49, 49-69, and the over 69-year-olds), the relative impact of frailty (using the Clinical Frailty Score; CFS), and disease severity (using National Early Warning Score; NEWS) on HRQoL domains. RESULTS: Overall mortality was 46.5% in admitted patients. In our SF-36 cohort (n=169), there was a significant reduction in all HRQoL domains versus normative data; the most significant reductions were in the physical component (p<0.001) across all ages and the emotional component (p<0.01) in the 49-69 year age group, with age having no additional impact on HRQoL. However, there was a significant correlation between physical well-being versus CFS (the correlation coefficient=-0.37, p<0.05), though not NEWS, with no gender difference observed. CONCLUSION: There was a significant reduction in all SF-36 domains at 1 year. Poor CFS at admission was associated with a significant and prolonged impact on physical parameters at 1 year. Age had little impact on the severity of HRQoL, except in the domains of physical functioning and the overall physical component.

Investigating the use and awareness of artificial sweeteners among diabetic patients in Bangladesh.

BACKGROUND: As with many countries around the world, the incidence of diabetes in Bangladesh is increasing significantly. Whilst there is controversy in the field regarding the health impact of artificial sweeteners in Western communities, the link between sweetener consumption and awareness in Bangladesh has not been established. METHODS: In the present study, 260 diabetic patients completed a questionnaire survey to investigate the use and awareness of sweeteners and how this links to demographics and potential co-morbidities. RESULTS: Findings show that daily artificial sweetener consumption is significantly associated with hypertension but not other co-morbidities such as kidney disease or obesity. We further demonstrate that there is limited checking of artificial sweeteners in food or drink products by participants. the rurality of diabetic participants was found to significantly correlates with lower awareness of any health impact of artificial sweeteners. CONCLUSIONS: The findings from this study demonstrate that there is a need to increase the awareness of artificial sweetener use in diabetic patients in Bangladesh. Combined with a more robust understanding of the health impact of artificial sweeteners, these findings suggest that there is potential to improve outcomes for diabetic patients by improving this awareness.

Laser doppler imaging - the role of poor burn perfusion in predicting healing time and guiding operative management.

AIM: To identify if the proportion of poor blood flow (blue) within an LDI (Laser doppler Imaging) image of a burn independently correlates with healing time. METHODS: Patient age, gender, burn type, and burn surface area were collected from the IBID (International Burn Injury Database). All LDI images were copied from the MoorLDI2-BI- Laser Doppler (MLDI) Scanner, onto Adobe Photoshop® version 2020 for pixel counting analysis and calculation of % TBSA (Total Body Surface Area) blue. Multiple linear regression analysis determined whether a proportional relationship was present for each parameter (age, gender, % TBSA Blue and comorbidities) with healing time. RESULTS: 110 patients with 197 burns were scanned with MLDI. Median age was 5 years (IQR 1-6). Median burn surface area was 1.5% (IQR 1-2.4). 56.4% of patients were male and patients were scanned an average of 2.68 days (SD±1.37) following burn injury. Number of physical comorbidities and age were found to have a statistically significant relationship with healing time (p = 0.03, p = 0.002). Gender and %TBSA blue did not have a statistically significant relationship with healing time (p = 0.07 and p = 0.058 respectively). We found a statistically significant difference in the mean healing time between burns with and without blue (3.43 weeks vs. 2.80 weeks, p = 0.0001). % TBSA Blue was more than four times higher in the operated group (0.48% vs. 0.11%) and was shown to have a statistically significant relationship with decision to operate (p = 0.027). Positive predictive value for the presence of blue on operative rate was 71.6%. Age, gender and number of comorbidities did not have a statistically significant influence on operative rate (p = 0.07, p = 0.50 and p = 0.49). CONCLUSION: % TBSA blue was not found to be a reliable independent indicator of burn healing time, but the presence of blue within an LDI image, advanced patient age and increased number of comorbidities did have a statistically significant relationship with healing time. This suggests their standardised inclusion into management decisions regarding intermediate depth burns is warranted.

Which frailty tool best predicts morbidity and mortality in ambulatory patients with heart failure? A prospective study.

BACKGROUND: Frailty is common in patients with heart failure (HF) and is associated with adverse outcome, but it is uncertain how frailty should best be measured. OBJECTIVES: To compare the prognostic value of commonly-used frailty tools in ambulatory patients with HF. METHODS AND RESULTS: We assessed, simultaneously, three screening tools [clinical frailty scale (CFS); Derby frailty index (DFI); acute frailty network (AFN) frailty criteria), three assessment tools (Fried criteria; Edmonton frailty score (EFS); deficit index (DI)) and three physical tests (handgrip strength, timed get-up-and-go test (TUGT), 5-metre walk test (5MWT)] in consecutive patients with HF attending a routine follow-up visit. 467 patients (67% male, median age = 76 years, median NT-proBNP = 1156 ng/L) were enrolled. During a median follow-up of 554 days, 82 (18%) patients died and 201 (43%) patients were either hospitalised or died. In models corrected for age, Charlson score, haemoglobin, renal function, sodium, NYHA, atrial fibrillation (AF), and body mass index, only log[NT-proBNP] and frailty were independently associated with all-cause death. A base model for predicting mortality at 1 year including NYHA, log[NT-proBNP], sodium and AF, had a C-statistic = 0.75. Amongst screening tools: CFS (C-statistic = 0.84); amongst assessment tools: DI (C-statistic = 0.83) and amongst physical test: 5MWT (C-statistic = 0.80), increased model performance most compared with base model (P <0.05 for all). CONCLUSION: Frailty is strongly associated with adverse outcomes in ambulatory patients with HF. When added to a base model for predicting mortality at 1 year including NYHA, NT-proBNP, sodium, and AF, CFS provides comparable prognostic information with assessment tools taking longer to perform.

Development and validation of a new antenatal warning score system (DRRiP) for neonatal complications of gestational diabetes.

OBJECTIVE: To evaluate the DRRiP (Diabetes Related Risk in Pregnancy) score warning system as a tool for predicting neonatal morbidity in gestational diabetes. METHODS: A retrospective observational cohort study. By applying nine parameters from an antenatal trichotomy of glycemic, ultrasound, and clinical characteristics, DRRiP scores were calculated and assigned to each patient using a checklist tool. Logistic regression models were used to evaluate the association between DRRiP score and adverse fetal outcomes, after adjusting for maternal age and body mass index (calculated as weight in kilograms divided by the square of height in meters). RESULTS: In all, 627 women were studied. DRRiP score was an excellent predictor of macrosomia and shoulder dystocia (both areas under the receiver operating characteristics curves [AUROC] = 0.86), and a modest predictor of preterm delivery, hyperbilirubinemia, neonatal intensive care unit admission and a composite of either of the studied events (AUROC range 0.63-0.69). For the composite outcome, the sensitivity of an amber trigger score of 1 was 68.7% (95% confidence interval [CI] 62.27%-74.63%) and specificity was 48.87% (95% CI 43.85%-53.9%). Specificity at a red trigger score of 3 (89.7%) and a graded increase in post-test probability (90.7% risk at a score of 5) were highly encouraging. CONCLUSION: DRRiP score offers reasonable discriminative performance that could be clinically useful for meaningful risk stratification when making delivery plans.

Prehabilitation for Patients Undergoing Orthopedic Surgery: A Systematic Review and Meta-analysis.

Importance: Prehabilitation programs for patients undergoing orthopedic surgery have been gaining popularity in recent years. However, the current literature has produced varying results. Objective: To evaluate whether prehabilitation is associated with improved preoperative and postoperative outcomes compared with usual care for patients undergoing orthopedic surgery. Data Sources: Bibliographic databases (MEDLINE, CINAHL [Cumulative Index to Nursing and Allied Health Literature], AMED [Allied and Complementary Medicine], Embase, PEDRO [Physiotherapy Evidence Database], and Cochrane Central Register of Controlled Trials) were searched for published trials, and the Institute for Scientific Information Web of Science, System for Information on Grey Literature in Europe, and European clinical trials registry were searched for unpublished trials from January 1, 2000, to June 30, 2022. Study Selection: Randomized clinical trials (RCTs) comparing prehabilitation with standard care for any orthopedic surgical procedure were included. Data Extraction and Synthesis: Two independent reviewers screened trials. Data were pooled using a random-effects model. Recommendations were determined using the Grading of Recommendations Assessment, Development and Evaluation system and the study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Pain, function, muscle strength, and health-related quality of life (HRQOL). Results: Forty-eight unique trials involving 3570 unique participants (2196 women [61.5%]; mean [SD] age, 64.1 [9.1] years) were analyzed. Preoperatively, moderate-certainty evidence favoring prehabilitation was reported for patients undergoing total knee replacement (TKR) for function (standardized mean difference [SMD], -0.70 [95% CI, -1.08 to -0.32]) and muscle strength and flexion (SMD, 1.00 [95% CI, 0.23-1.77]) and for patients undergoing total hip replacement (THR) for HRQOL on the 36-item Short Form Health Survey (weighted mean difference [WMD], 7.35 [95% CI, 3.15-11.54]) and muscle strength and abduction (SMD, 1.03 [95% CI, 0.03-2.02]). High-certainty evidence was reported for patients undergoing lumbar surgery for back pain (WMD, -8.20 [95% CI, -8.85 to -7.55]) and moderate-certainty evidence for HRQOL (SMD, 0.46 [95% CI, 0.13-0.78]). Postoperatively, moderate-certainty evidence favoring prehabilitation was reported for function at 6 weeks in patients undergoing TKR (SMD, -0.51 [95% CI, -0.85 to -0.17]) and at 6 months in those undergoing lumbar surgery (SMD, -2.35 [95% CI, -3.92 to -0.79]). Other differences in outcomes favoring prehabilitation were of low to very low quality of evidence. Conclusions and Relevance: In this systematic review and meta-analysis of RCTs, moderate-certainty evidence supported prehabilitation over usual care in improving preoperative function and strength in TKR and HRQOL and muscle strength in THR, high-certainty evidence in reducing back pain, and moderate-certainty evidence in improving HRQOL in lumbar surgery. Postoperatively, moderate-certainty evidence supported prehabilitation for function following TKR at 6 weeks and lumbar surgery at 6 months. Prehabilitation showed promising results for other outcomes, although high risk of bias and heterogeneity affected overall quality of evidence. Additional RCTs with a low risk of bias investigating preoperative and postoperative outcomes for all orthopedic surgical procedures are required.

Ulinastatin in the treatment of severe acute pancreatitis: A single-center randomized controlled trial.

BACKGROUND: Severe acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract and carries a significant financial burden with high disability and mortality. There are no effective drugs in the clinical management of severe AP, and there is an absence of evidence-based medicine concerning the treatment of severe AP. AIM: To explore whether ulinastatin (UTI) can improve the outcome of severe AP. METHODS: The present research included patients who were hospitalized in intensive critical care units (ICUs) after being diagnosed with severe AP. Patients received UTI (400000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were 7-d mortality, clinical efficacy, inflammatory response, coagulation function, infection, liver function, renal function, and drug-related adverse effects were evaluated. RESULTS: A total of 181 individuals were classified into two groups, namely, the placebo group (n = 90) and the UTI group (n = 91). There were no statistically significant differences in baseline clinical data between the two groups. The 7-d mortality and clinical efficacy in the UTI group were remarkably improved compared with those in the placebo group. UTI can protect against hyperinflammation and improve coagulation dysfunction, infection, liver function, and renal function. UTI patients had markedly decreased hospital stays and hospitalization expenditures compared with the placebo group. CONCLUSION: The findings from the present research indicated that UTI can improve the clinical outcomes of patients with severe AP and has fewer adverse reactions.

Changes in absolute flow, myocardial resistance and FFR after chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Randomised studies of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) have shown inconsistent outcomes, suggesting incomplete understanding of this cohort and their coronary physiology. To address this shortcoming, we designed a prospective observational study to measure the recovery of absolute coronary blood flow following successful CTO PCI Aims: We sought to identify patient and procedural characteristics associated with a favourable physiological outcome after CTO PCI. METHODS: Consecutive patients with a CTO subtending viable myocardium underwent PCI utilising contemporary techniques and the hybrid algorithm. Immediately after PCI, and at 3-month follow-up, physiological measurements were performed utilising continuous thermodilution. RESULTS: A total of 81 patients were included with a mean age of 63.6±8.9 years, and 66 (81.5%) were male. Physiological measurements of absolute coronary blood flow in the CTO vessel increased by 30% (p<0.001) and microvascular resistance reduced by 16% (p<0.001) from immediately post-CTO PCI to follow-up assessment. Fractional flow reserve increased by 0.02 (p=0.015) in the same period. Prior coronary artery bypass graft (CABG) and a higher estimated glomerular filtration rate (eGFR) were associated with a larger change in absolute flow. An extraplaque strategy was associated with a smaller change in absolute flow. CONCLUSIONS: Post-CTO PCI, there is a continued augmentation in absolute coronary blood flow and reduction in microvascular resistance from baseline to follow-up at 3 months. Prior CABG and a higher baseline eGFR were predictors of a larger change in absolute coronary flow, whilst an extraplaque final wire path strategy predicted a smaller change. Lastly, the patient characteristics and comorbidities had a larger influence than procedural factors on the observed change in absolute flow.