Delay In Treatment Research Articles

Minimal Transfer of Atorvastatin and Its Metabolites in Human Milk: A Case Series.

Background: Statins are historically contraindicated during breastfeeding due to theoretical concerns of disruptions in infant development from drug exposure and nutritional changes in milk. Breastfeeding mothers requiring statins often discontinue statins or postpone treatment until breastfeeding cessation, contributing to delays in treatment up to 14 years. This study aims to determine the transfer of atorvastatin and its active metabolites into human milk and evaluate the infant's risk of drug exposure. Materials and Methods: Milk samples and health information were released from the InfantRisk Human Milk Biorepository for three women taking 20 mg, 40 mg, and 80 mg of atorvastatin daily at steady state conditions. The concentration of atorvastatin (AT) and its active metabolites, ortho-hydroxy AT (2OH AT) and para-hydroxy AT (4OH AT), was quantified in timed milk samples using liquid chromatography-mass spectrometry. Results: The highest absolute infant dose of AT was 0.00027 mg/kg/day, and the highest weight-adjusted relative infant dose of the combined analytes was 0.09%, far below established thresholds for infant safety. Milk cholesterol levels were within previously established norms in the range of 10 mg/dL. The mothers reported no adverse outcomes in the two exposed infants. Conclusions: The transfer of atorvastatin and its metabolites was exceedingly low. While the impact on milk composition in states of hyperlipidemia (whether treated or untreated) is not well understood, it is unlikely that the drug in the milk would be present in clinically significant levels to adversely affect a breastfed infant.

Transforming respiratory tract infection diagnosis in the kingdom of saudi arabia through point-of-care testing: A white paper for policy makers

With the evident increased prevalence of respiratory tract infections (RTIs) such as Respiratory Syncytial Virus (RSV), influenza, Group A Streptococcus (GAS), and COVID-19, the conventional diagnostic methods are considered sub-optimal in providing timely management to patients in the Kingdom of Saudi Arabia (KSA). Gaps in current diagnostics are magnified by the Kingdom's unique demographic composition, comprising 11.9 million foreign workers, and the annual influx of over 10 million pilgrims. Current gaps in timely diagnosis leads to delays in treatment, misuse of antibiotics, and protracted hospital stays, subsequently compromising patient care, and escalating healthcare costs. KSA healthcare stakeholders suggest that the integration of rapid molecular Point-of-Care Testing (POCT) into the Kingdom's healthcare infrastructure is an absolute necessity. This publication serves as an urgent call for action aimed at healthcare policymakers in Saudi Arabia, to review the existing diagnostic challenges and include rapid POCTs in the Saudi healthcare strategy for respiratory infections.

Data-Driven Strategies for Carbimazole Titration: Exploring Machine Learning Solutions in Hyperthyroidism Control.

University Hospitals Dorset (UHD) has over 1,000 thyroid patient contacts annually. These are primarily patients with autoimmune hyperthyroidism treated with Carbimazole titration. Dose adjustments are made by a healthcare professional (HCP) based on the results of thyroid function tests, who then prescribes a dose and communicates this to the patient via letter. This is time-consuming and introduces treatment delays. This study aimed to replace some time-intensive manual dose adjustments with a machine learning model to determine Carbimazole dosing. This can in the future serve patients with rapid and safe dose determination and ease the pressures on HCPs. Data from 421 hyperthyroidism patients at UHD were extracted and anonymised. A total of 353 patients (83.85%) were included in the study. Different machine-learning classification algorithms were tested under several data processing regimes. Using an iterative approach, consisting of an initial model selection followed by a feature selection method the performance was improved. Models were evaluated using weighted F1 scores and Brier scores to select the best model with the highest confidence. The best performance is achieved using a random forest (RF) approach, resulting in good average F1 scores of 0.731. A model was selected based on a balanced assessment considering the accuracy of the prediction (F1 = 0.751) and the confidence of the model (Brier score = 0.38). To simulate a use-case, the accumulation of the prediction error over time was assessed. It was determined that an improvement in accuracy is expected if this model was to be deployed in practice.

Surface-enhanced Raman spectroscopy (SERS) for the diagnosis of acute myocardial infarction (AMI) using blood serum samples.

Acute myocardial infarction (AMI) is a serious medical condition generally known as heart attack, which is caused by the decreased or completely blocked blood flow to a part of the heart muscle. It is a significant cause of both mortality and morbidity throughout the world. Cardiac troponin-I (cTnI) is an important biomarker at different stages of AMI and is one of the most specific and widely used cardiac skeletal muscle proteins. Delays in medical treatment and inaccurate diagnosis might be the main cause of death of AMI patients. To overcome the death rate of AMI patients, early diagnosis of this disease is crucial. In the current study, surface-enhanced Raman spectroscopy (SERS) is employed for the characterization and diagnosis of this disease using blood serum samples from 49 clinically confirmed acute myocardial infarction (AMI) patients and 17 healthy persons. Silver nanoparticles (AgNPs) are used as the SERS substrate for the recognition of characteristic SERS spectral features, differentiating between healthy and AMI-positive samples. The acute myocardial infarction-positive blood serum samples reveal remarkable differences in spectral intensities at 534, 697, 744, 835, 927, 941, 988, 1221, 1303, 1403, 1481, 1541, 1588 and 1694 cm-1. For the differentiation and quantitative analysis of the SERS spectra, multivariate chemometric tools (including principal component analysis (PCA) and partial least squares regression (PLSR)) are employed. A PLSR model established on the basis of differentiating the SERS spectral features is found to be helpful in the prediction of the levels of cardiac troponin-I (cTnI) in the blood serum samples with the root mean square error of calibration (RMSEC) value of 2.98 ng mL-1 and root mean square errors of prediction (RMSEP) value of 3.98 ng mL-1 for S7.

Association between ossific nucleus volume changes and postoperative avascular necrosis risk in children with developmental dysplasia of the hip

This study aimed to investigate the correlation between ossific nucleus volume and avascular necrosis (AVN) in pediatric patients diagnosed with developmental dysplasia of the hip (DDH). Analyzing 211 cases, including 119 open reduction (OR) and 92 closed reduction (CR) procedures, we quantified ossific nucleus volume using magnetic resonance imaging (MRI). Categorizing the OR group based on ossific nucleus volume revealed no statistically significant difference in AVN incidence. Similarly, in the CR cohort, there was no significant discrepancy in AVN occurrence between subgroups with or without the ossific nucleus. Logistic regression in CR identified the international hip dysplasia institute (IHDI) grade as a significant AVN risk factor (p = 0.007). IHDI grades 3 and 4 exhibited a 6.94 times higher likelihood of AVN compared to grades 1 and 2. Across CR and OR, neither initial age nor ossific nucleus volume emerged as AVN risk factors. In conclusion, ossific nucleus volume does not pose a risk for AVN in DDH children undergoing CR or OR, emphasizing the clinical significance of IHDI grading in predicting AVN risk during CR and the importance of early intervention to prevent treatment delays.

Benefits of Early Versus Late Initiation of Intravenous Immunoglobulin in the Treatment of Patients With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Immune-Mediated Necrotizing Myopathy.

No clinical trials have been conducted to establish optimal and effective treatment in patients with immune-mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti-HMGCR IMNM. We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti-HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti-HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti-HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti-HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria. Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0-month time point. At the 0-month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12-month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did. Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti-HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long-term disability.

Macular Optical Coherence Tomography Findings in Patients With Syphilitic Optic Neuropathy-A Case Series and Systematic Review.

Syphilis is a sexually or congenitally acquired infectious disease that can affect multiple organs systems, including the eye. When left undiagnosed and untreated, it can lead to significant morbidity and mortality. Syphilitic optic neuropathy can be difficult to diagnose because it can mimic many other nonsyphilitic causes of optic nerve involvement, leading to delay in treatment. Diagnosing ocular syphilis may be facilitated by assessing for specific outer retina abnormalities on macular optical coherence tomography (OCT). This was a case series and case-based systematic review. For the case series, a retrospective chart review was conducted of all patients who presented to a tertiary university-affiliated neuro-ophthalmology practice over 6 months with undifferentiated optic neuropathy and were eventually diagnosed with syphilitic optic neuropathy. For the systematic review, OVID MEDLINE, EMBASE, and COCHRANE CENTRAL databases were searched to identify all cases of syphilitic optic neuropathy with macular OCT. The primary research outcome was the prevalence of cases with outer retinal abnormalities on OCT. Four cases were identified that were eligible for inclusion. The ages ranged from 27 to 62 years old, and 2 of the patients were female. On examination, vision ranged from Snellen 20/50 to hand motion; all patients had optic neuropathy, and macular OCT revealed chorioretinitis characterized by retinal pigment epithelium (RPE) excrescences. The patients subsequently underwent uveitis workup and were diagnosed with syphilis. They were treated with intravenous penicillin and showed improvement in outer retina appearance on follow-up. The systematic review consisted of 24 cases and 35 eyes with syphilitic optic neuropathy and reported macular OCT findings. Eighty-three percent (20/24) were males, and the mean age was 47.7 years (SD: 49.2). The mean visual acuity at presentation was Snellen 20/57. On fundoscopy, 25.7% (9/35) of eyes had vitritis, whereas 22.8% (8/35) had placoid chorioretinal lesions. On OCT, 45.7% (16/35) of eyes had abnormal outer retina findings, most commonly disruption of the ellipsoid zone (EZ) and/or RPE excrescences. All patients were treated with penicillin or ceftriaxone, and final mean visual acuity was Snellen 20/29. All 4 patients identified in the case series, and nearly half of patients with syphilitic optic neuropathy described in the literature had concurrent-specific outer retina abnormalities (disruption of EZ and/or placoid chorioretinitis in the form of RPE excrescences) seen on macular OCT. We recommend that clinicians obtain macular OCT for all patients presenting with undifferentiated optic neuropathy.

Systemic lupus erythematosus: An imitator for inflammatory bowel disease

AbstractSystemic lupus erythematosus (SLE) is a systemic autoimmune disease that may involve any organ in the body. Inflammation of the bowel wall as a presenting symptom of SLE is uncommon and can lead to delays in diagnosis and treatment. Here, we discuss the case of an adolescent male who presented with weight loss, intermittent fevers, abdominal pain, vomiting, and diarrhea. Initially, inflammatory bowel disease (IBD) was suspected, but endoscopic evaluation did not support this diagnosis. A computed tomography scan of the abdomen revealed signs of serositis, concerning for an inflammatory process and the patient was referred to Rheumatology for further evaluation. Autoimmune serologies were obtained and combined with clinical findings confirmed a diagnosis of SLE. This case advances our understanding of SLE as a multisystemic disease and highlights an unusual presentation involving the gastrointestinal tract, which can mimic IBD and potentially delay the diagnosis and treatment process.

RvXmBlendNet: A Multi-architecture Hybrid Model for Improved Skin Cancer Detection

AbstractSkin cancer, one of the most dangerous cancers, poses a significant global threat. While early detection can substantially improve survival rates, traditional dermatologists often face challenges in accurate diagnosis, leading to delays in treatment and avoidable fatalities. Deep learning models like CNN and transfer learning have enhanced diagnosis from dermoscopic images, providing precise and timely detection. However, despite the progress made with hybrid models, many existing approaches still face challenges, such as limited generalization across diverse datasets, vulnerability to overfitting, and difficulty in capturing complex patterns. As a result, there is a growing need for more robust and effective hybrid models that integrate multiple architectures and advanced mechanisms to address these challenges. Therefore, this study aims to introduce a novel multi-architecture hybrid deep learning model called "RvXmBlendNet," which combines the strengths of four individual models: ResNet50 (R), VGG19 (v), Xception (X), and MobileNet (m), followed by "BlendNet" to signify their fusion into a unified architecture. The integration of these models is achieved through a synergistic combination of architectures, incorporating self-attention mechanisms using attention layers and adaptive content blocks. This study used the HAM10000 dataset to refine dermoscopic image preprocessing and enhance deep learning model accuracy. Techniques like OpenCV-based hair removal, min–max scaling, and adaptive histogram equalization were employed to improve image quality and feature extraction. A comparative study between the proposed hybrid "RvXmBlendNet" and individual models (CNN, ResNet50, VGG19, Xception, and MobileNet) demonstrated that "RvXmBlendNet" achieved the highest accuracy of 98.26%, surpassing other models. These results suggest that the system can facilitate earlier interventions, improve patient outcomes, and potentially lower healthcare costs by reducing the need for invasive diagnostic procedures.

Validity of a Smartphone App to Objectively Monitor Performance Outcomes in Degenerative Cervical Myelopathy: Preliminary Findings From a Longitudinal Observational Study

Background Developing new clinical measures for degenerative cervical myelopathy (DCM) is an AO Spine RECODE-DCM research priority. Difficulties detecting DCM, and changes in DCM, cause diagnostic and treatment delays in clinical settings and heightened costs in clinical trials due to elevated recruitment targets. Digital outcome measures can tackle these challenges due to their ability to measure disease remotely, repeatedly, and more economically. Objective The study aims to assess the validity of MoveMed, a battery of performance outcome measures performed using a smartphone app, in the measurement of DCM. Methods A prospective observational study in decentralized secondary care was performed in England, United Kingdom. Validity and risk of bias were assessed using criteria from the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) manual. Each MoveMed outcome was compared with 2 patient-reported comparators, with a priori hypotheses of convergence or divergence tested against consensus thresholds. The primary outcome was the correlation coefficient between the MoveMed outcome and the patient-reported comparators. The secondary outcome was the percentage of correlations that aligned with the a priori hypotheses. The comparators used were the patient-derived modified Japanese Orthopaedic Association score and the World Health Organization Quality of Life Brief Version questionnaire. Thresholds for convergence or divergence were set at ≥0.3 for convergence, &lt;0.3 for divergence, and &gt;0/&lt;0 for directionality. Results A total of 27 adults aged 60 (SD 11) years who live with DCM and possess an approved smartphone were included in a preliminary analysis. As expected, MoveMed tests of neuromuscular function correlated most with questionnaires of neuromuscular function (≥0.3) and least with questionnaires of quality of life (&lt;0.3). Furthermore, directly related constructs correlated positively to each other (&gt;0), while inversely related constructs correlated negatively (&lt;0). Overall, 74% (67/90) and 47% (8/17) of correlations (unidimensional and multidimensional, respectively) were in accordance with hypotheses. No risk-of-bias factors from the COSMIN Risk of Bias checklist were recorded. Overall, this was equivalent to “very good” quality evidence of sufficient construct validity in DCM. Conclusions MoveMed outcomes and patient-reported questionnaires converge and diverge in accordance with expectations. These findings support the validity of the MoveMed tests in an adult population living with DCM. Criteria from COSMIN provide “very good” quality evidence to support this.

Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis. We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables. One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5-524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5-945.0)) vs. (17.0 (IQR: 8.0-30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis. Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings.

WP7.12 - The Impact of a ‘Golden Abscess Pathway’ in a Tertiary Teaching Hospital to Optimize Acute Abscess Management

Abstract Introduction The 'Golden Patient' initiative targets operating room efficiency by pre-selecting initial patients, especially beneficial for non-urgent emergencies like abscesses. Anorectal abscesses often face treatment delays due to the prioritization of critical cases. WSES guidelines advocate prompt incision and drainage (I&amp;D) within 24 hours, recommending outpatient management for suitable patients. This study aims to establish an ambulatory 'Golden Abscess Pathway' in a tertiary teaching hospital and assess its impact on acute abscess management efficiency. Patients and Methods This retrospective study at the Leeds Institute of Emergency General Surgery included individuals undergoing I&amp;D for acute abscesses. The pre-pathway cohort spanned 03/01/2023 to 28/04/2023, with the 'Golden Abscess Pathway' implemented on 19/06/2023. The post-pathway cohort covered 19/06/2023 to 16/10/2023. The analysis focused on patient demographics and intervention timelines. Results The study included 199 patients, with 93 pre-pathway (55M: 38F, mean age 34.3 ± 14.5 years) and 106 post-pathway (70M: 36F, mean age 35.4 ± 13.3 years). The 'Golden Abscess Pathway' reduced the average duration from consultation to operation (1.73 days vs. 2.75 days), advanced median operation start time (09:20 vs. 09:47), and decreased overnight stays (34.9% vs. 44.1%). Conclusion Implementation of the 'Golden Abscess Pathway' demonstrated positive outcomes, reducing delays in patient management. These results highlight the pathway's potential to enhance efficiency and overall patient care in acute abscess management.

The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer.

Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 dayswas calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy.

Mitigating Risks in Cone Beam Computed Tomography Guided Online Adaptive Radiation Therapy: A Preventative Reference Planning Review Approach

PurposeOnline adaptive radiotherapy (oART) treatment planning requires evaluating the temporal robustness of reference plans, anticipating the potential changes during treatment courses that may even lead to risks unique to the adaptive workflow. This study conducted a risk analysis of the CBCT-guided adaptive workflow and is the first to assess an adaptive specific reference planning review that mitigates risk in the planning process to prevent events and treatment deficiencies during adaptation. Methods and MaterialsA quality management team of medical physicists, residents, physicians, and radiation therapists performed a fault tree analysis, and failure mode and effects analysis (FMEA). Fault trees were created for under/overdosing targets, treatment deficiencies, as well as assisted in identifying failure modes for the FMEA. Treatment deficiency was defined to include a non-ideal oART plan resulting in treatment with a lower quality plan (either oART or scheduled plan), treatment delay, or cancelling treatment for the day. A reference planning checklist was created to catch failure modes before reaching the patient. Risk priority numbers (RPN=Severity*Detectability*Occurrence) were scored with and without the reference planning checklist to quantify risk mitigation. A root cause analysis was conducted for an event where an adaptive plan failed to generate. ResultsThe reference planning checklist (with items covering patient background, contouring/planning robustness for anatomy variability, and machine limitations) reduced the RPN for all failure modes. Only 1 failure mode with a risk priority number >150 occurred with the reference planning checklist compared to 29 failure modes without, including 14 adaptive specific failure modes. Contouring, planning, setup, scheduling, and documentation errors were identified during the fault tree analysis. 29/70 errors were adaptive specific. The reference planning checklist could address 23/33 for over/under dosing and 28/37 errors for treatment deficiency. The root cause analysis highlighted the need for checking setup prior to adaptive plan delivery, and time-out checklist. ConclusionsThe reference planning checklist improved detection of the failure modes and improves the quality and robustness of the plans produced for oART. It is ideally performed before physician plan review to prevent last minute re-plan (before or after first adaptive treatment) and delay of patient start. The checklist presented can be modified based on failures specific to individual clinics and utilized at various planning steps based on available resources.

Diagnosis and management of Clostridioides difficile in inflammatory bowel disease.

Patients with IBD have an increased risk for Clostridioides difficile infection (CDI), which can lead to worse IBD outcomes. The diagnosis of CDI in IBD patients is complicated by higher C. difficile colonization rates and shared clinical symptoms of intestinal inflammation. Traditional risk factors for CDI, such as antibiotic exposure, may be lacking in IBD patients due to underlying intestinal microbiota dysbiosis. While CDI disproportionately affects people with IBD, patients with IBD are typically excluded from CDI clinical trials creating a knowledge gap in the diagnosis and management of these two diseases. This narrative review aims to provide a comprehensive overview of the diagnosis, treatment, and prevention of CDI in IBD patients. Distinguishing CDI from C. difficile colonization in the setting of an IBD exacerbation is important to avoid treatment delays. When CDI is diagnosed, extended courses of anti-C. difficile antibiotics may lead to better CDI outcomes. Regardless of a diagnosis of CDI, the presence of C. difficile in an IBD patient should prompt a disease assessment of the underlying IBD. Microbiota-based therapies and bezlotoxumab appear to be effective in preventing CDI recurrence in IBD patients. Patients with IBD should be considered high risk for CDI recurrence and evaluated for a preventative strategy when diagnosed with CDI. Ultimately, the co-management of CDI in an IBD patient requires a nuanced, patient-specific approach to distinguish CDI from C. difficile colonization, prevent CDI recurrence, and manage the underlying IBD.

Unilateral amelanotic conjunctival malignant melanoma: a case report

IntroductionCutaneous malignant melanomas rarely occur in the eye, usually in the eyelids or the conjunctiva. Conjunctival malignant melanomas are even rarer. Most melanomas are dark in color as they are pigmented. However, amelanotic conjunctival malignant melanomas, a scarce variant of the cancer, can be challenging to diagnose accurately.Case presentationWe present two cases of white Caucasian Swedish-born women who were diagnosed with unilateral amelanotic malignant melanoma in the conjunctiva of the eye. In the first case, the patient was an 81-year-old woman who was suffering from redness and foreign body sensation in the left eye. The initial diagnosis was blepharitis. Three biopsies were taken, which showed malignant melanoma in the eyelid and the conjunctiva. Unfortunately, the eye and the rest of the orbit could not be saved, and the patient had to undergo an orbital exenteration. In the second case, the patient was a 50-year-old woman, and the tumor was localized in the temporal conjunctiva of the left eye. The initial diagnosis was pinguecula, but at the time of surgery, the physician suspected conjunctival intraepithelial neoplasia. The tumor was not completely removed, so adjuvant brachytherapy and local chemotherapy were used. The eye was preserved. No neck and/or lung metastasis was detected in either case at the time of diagnosis.ConclusionsConjunctival amelanotic malignant melanomas should be suspected when tumors are present in the eye and/or the eyelids. By suspecting amelanotic malignant melanoma, the delay in treatment can be shortened. Treating them as soon as possible is essential to minimize the risk of metastasis.

Real-world experience in treatment of donor-derived Hepatitis C virus in kidney transplant recipients with delayed initiation, shortened course glecaprevir/pibrentasvir versus standard of care.

There is limited literature describing the real-world practice of delayed initiation and shortened duration direct-acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1-week post-transplant. Retrospective study of HCV-negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections. 102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups. CONCLUSION: Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.

Association between time to treatment and bladder cancer survival: a population-based analysis.

Cancer treatment delay is a global health system issue. However, data concerning the impact of treatment delays on survival in bladder cancer remain controversial. This study sought to evaluate the impact of time from diagnosis to treatment on survival outcomes of bladder cancer patients in the US Surveillance, Epidemiology, and End Results (SEER) database. The SEER was searched from 2000 to 2020 for bladder cancer patients. Logistical regression was used to explore potential factors related to treatment delay. Kaplan-Meier curves were generated to investigate the overall and cancer-specific survival. Multivariate Cox proportional hazards regression models were used to evaluate the effects of covariables on survival outcomes in bladder cancer with treatment delay. There were 12,686 eligible patients included in this study. A total of 2,379 patients experienced an initial treatment delay. Initial treatment delay was related to worse survival. Sex, age, pathological grade, clinical stage, and surgery were associated with increased odds of initial treatment delay. In the patients with initial treatment delay, age, advanced stage, lymph node involvement, high pathological grades and metastasis were independent predictors of poor overall survival and cancer-specific survival, while marital status at diagnosis, surgery, chemotherapy, and radiotherapy were found to improve both overall survival and cancer-specific survival. Significant disparities in pathological/clinical variables could contribute to treatment delay. Surgery, chemotherapy, and radiotherapy benefited the survival of patients with treatment delays.

ENTIMOS: Decision Support Tool Highlights Potential Impact of Non-intravenous Therapies for Multiple Sclerosis on Patient Care via Clinical Scenario Simulation.

Administration of intravenous (IV), high-efficacy treatments (HETs) for the treatment of multiple sclerosis (MS) poses a high resourcing and planning burden on infusion centres, resulting in treatment delays that may increase the risk of breakthrough disease activity. Simulation tools can be used to systematically analyse capacity scenarios and identify and better understand constraints, therefore enabling decision-makers to optimise patient care. We have previously applied ENTIMOS, a discrete event simulation model, to assess scenarios of patient flow and care delivery using real-life data inputs from the neurology infusion suite at Charing Cross Hospital London. The model predicted that, given current capacity and projected demand, patients would experience high-risk treatment delays within 30 months. This study aimed to address key healthcare challenges for MS patient care management as seen from a neurologist's perspective. We used ENTIMOS to predict the impact of several distinct and clinically plausible scenarios on patient waiting times at the same MS infusion suite and to quantify mitigation strategies needed to assure continuity of care. We used real-world experience of an expert neurologist to identify five clinical scenarios: (1) switching patients to a subcutaneous (SC) MS treatment of the same therapeutic agent, in the same hospital setting; (2) extending opening times to the weekend; (3) reducing the number of infusion chairs (to simulate social distancing measures applied during the coronavirus disease 2019 [COVID-19] pandemic); (4) increasing demand for infusions; and (5) increasing the scheduling approval time. Patient waiting time for next due infusion and time to high-risk treatment delays (≥ 30 days) were the main analysed model outputs. Previously published base case results were used as reference. All hypothetical scenarios were run over a 3-year horizon (with the exception of scenario 1, which was run over a 3- and 5-year horizon). Strategies to mitigate treatment delays were analysed and discussed. Switching 50% of patients to SC treatment of the same therapeutic agent administered in hospital postponed the predicted high-risk treatment delays to shortly beyond the 3-year simulation timeframe (month 38). Weekend opening reduced waiting times from 20 days to 4 days and prevented treatment delays, however, at elevated labour costs. Reducing the infusion chairs increased waiting time to 53 days on average and 86 days at the end of the simulation, leading to high-risk treatment delays within 6 months. An increased demand for infusions increased waiting time to 26 days on average and 47 days at the end of the simulation, leading to high-risk treatment delays within 22 months. Prolonged scheduling approval time did not reduce the waiting time, nor postpone the high-risk treatment delays. Decision makers need transparency on capacity constraints to better plan resourcing at infusion suites and MS treatments. Our results showed that various mitigation measures, such as increasing capacity by additional infusion chairs per year and transferring patients to other infusion suites, may help prevent treatment delays. Switching patients from IV to an SC version of the same therapeutic agent reduced the waiting time moderately and postponed high-risk treatment delays. It was insufficient to prevent high-risk treatment delays in the long term.

Impact of awareness and time-delayed saturated treatment on the transmission of infectious diseases

We have proposed a mathematical model with saturated incidence and treatment rates along with awareness and delay in treatment. We analyze the model and find the equilibrium points and their stability. We also find the basic reproduction number R0 to understand the disease dynamics. For R0=1, we get transcritical backward bifurcation which means that the disease persists in the population even if R0<1. We performed the sensitivity analysis and found that treatment along with awareness plays a significant role in controlling infectious disease. We deduce that awareness about the disease affects the transmission rate of infection. As people become aware of aspects of the infectious disease, they amend their behavior so that they fend themselves from catching the disease. We have introduced a time lag in treatment and found the threshold value of the time delay. It is observed that when the value of the time delay crosses the threshold value, we get a Hopf bifurcation i.e. endemic steady state becomes unstable above the threshold value and it may become difficult to control the disease beyond the threshold value of delay in treatment.