Risk Model-Based Lung Cancer Screening : A Cost-Effectiveness Analysis.

BACKGROUND: In their 2021 lung cancer screening recommendation update, the U.S. Preventive Services Task Force (USPSTF) evaluated strategies that select people based on their personal lung cancer risk (risk model-based strategies), highlighting the need for further research on the benefits and harms of risk model-based screening. OBJECTIVE: To evaluate and compare the cost-effectiveness of risk model-based lung cancer screening strategies versus the USPSTF recommendation and to explore optimal risk thresholds. DESIGN: Comparative modeling analysis. DATA SOURCES: National Lung Screening Trial; Surveillance, Epidemiology, and End Results program; U.S. Smoking History Generator. TARGET POPULATION: 1960 U.S. birth cohort. TIME HORIZON: 45 years. PERSPECTIVE: U.S. health care sector. INTERVENTION: Annual low-dose computed tomography in risk model-based strategies that start screening at age 50 or 55 years, stop screening at age 80 years, with 6-year risk thresholds between 0.5% and 2.2% using the PLCOm2012 model. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) and cost-effectiveness efficiency frontier connecting strategies with the highest health benefit at a given cost. RESULTS OF BASE-CASE ANALYSIS: Risk model-based screening strategies were more cost-effective than the USPSTF recommendation and exclusively comprised the cost-effectiveness efficiency frontier. Among the strategies on the efficiency frontier, those with a 6-year risk threshold of 1.2% or greater were cost-effective with an ICER less than $100 000 per quality-adjusted life-year (QALY). Specifically, the strategy with a 1.2% risk threshold had an ICER of $94 659 (model range, $72 639 to $156 774), yielding more QALYs for less cost than the USPSTF recommendation, while having a similar level of screening coverage (person ever-screened 21.7% vs. USPSTF's 22.6%). RESULTS OF SENSITIVITY ANALYSES: Risk model-based strategies were robustly more cost-effective than the 2021 USPSTF recommendation under varying modeling assumptions. LIMITATION: Risk models were restricted to age, sex, and smoking-related risk predictors. CONCLUSION: Risk model-based screening is more cost-effective than the USPSTF recommendation, thus warranting further consideration. PRIMARY FUNDING SOURCE: National Cancer Institute (NCI).

Comparison of Primary Closure, Secondary Closure, and Limberg Flap in the Surgical Treatment of Pilonidal Cysts.

There are few studies comparing methods for pilonidal cyst closure. This study was conducted to compare simple surgical closure, secondary healing, and closure using a Limberg flap in the treatment of patients affected with pilonidal cysts. In total, 150 patients with pilonidal cysts were selected and randomized into 3 groups, with 50 participants in each group. Group A underwent primary closure, Group B underwent secondary closure, and Group C underwent closure with a Limberg flap. Operating time, amount of pain after surgery, time to mobilization, time until return to work, time for complete healing, time until being able to sit on the toilet without pain, postoperative complications including infection and recurrence, and seroma and edema after surgery were compared among the 3 groups. Duration of surgery in the Limberg flap group was significantly longer than the duration of surgery in Group A or Group B (p < .001). The time to patient mobilization, the time when the patient returned to work, the time to complete healing, and the time to being able to sit on the toilet without pain were significantly shorter in Group C than in Group A or Group B (p < .001). Although the procedure takes longer when using a Limberg flap, it appears to be a more effective method in the surgical treatment of patients with pilonidal cyst because of the reduced healing time and improved functional status after the procedure.

Markov models for clinical decision-making in radiation oncology: A systematic review.

The intrinsic stochasticity of patients' response to treatment is a major consideration for clinical decision-making in radiation therapy. Markov models are powerful tools to capture this stochasticity and render effective treatment decisions. This paper provides an overview of the Markov models for clinical decision analysis in radiation oncology. A comprehensive literature search was conducted within MEDLINE using PubMed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies published from 2000 to 2023 were considered. Selected publications were summarized in two categories: (i) studies that compare two (or more) fixed treatment policies using Monte Carlo simulation and (ii) studies that seek an optimal treatment policy through Markov Decision Processes (MDPs). Relevant to the scope of this study, 61 publications were selected for detailed review. The majority of these publications (n = 56) focused on comparative analysis of two or more fixed treatment policies using Monte Carlo simulation. Classifications based on cancer site, utility measures and the type of sensitivity analysis are presented. Five publications considered MDPs with the aim of computing an optimal treatment policy; a detailed statement of the analysis and results is provided for each work. As an extension of Markov model-based simulation analysis, MDP offers a flexible framework to identify an optimal treatment policy among a possibly large set of treatment policies. However, the applications of MDPs to oncological decision-making have been understudied, and the full capacity of this framework to render complex optimal treatment decisions warrants further consideration.

Cluster-Based Toxicity Estimation of Osteoradionecrosis Via Unsupervised Machine Learning: Moving Beyond Single Dose-Parameter Normal Tissue Complication Probability by Using Whole Dose-Volume Histograms for Cohort Risk Stratification.

PURPOSE: Given the limitations of extant models for normal tissue complication probability estimation for osteoradionecrosis (ORN) of the mandible, the purpose of this study was to enrich statistical inference by exploiting structural properties of data and provide a clinically reliable model for ORN risk evaluation through an unsupervised-learning analysis that incorporates the whole radiation dose distribution on the mandible. METHODS AND MATERIALS: The analysis was conducted on retrospective data of 1259 patients with head and neck cancer treated at The University of Texas MD Anderson Cancer Center between 2005 and 2015. During a minimum 12-month posttherapy follow-up period, 173 patients in this cohort (13.7%) developed ORN (grades I to IV). The (structural) clusters of mandibular dose-volume histograms (DVHs) for these patients were identified using the K-means clustering method. A soft-margin support vector machine was used to determine the cluster borders and partition the dose-volume space. The risk of ORN for each dose-volume region was calculated based on incidence rates and other clinical risk factors. RESULTS: The K-means clustering method identified 6 clusters among the DVHs. Based on the first 5 clusters, the dose-volume space was partitioned by the soft-margin support vector machine into distinct regions with different risk indices. The sixth cluster entirely overlapped with the others; the region of this cluster was determined by its envelopes. For each region, the ORN incidence rate per preradiation dental extraction status (a statistically significant, nondose related risk factor for ORN) was reported as the corresponding risk index. CONCLUSIONS: This study presents an unsupervised-learning analysis of a large-scale data set to evaluate the risk of mandibular ORN among patients with head and neck cancer. The results provide a visual risk-assessment tool for ORN (based on the whole DVH and preradiation dental extraction status) as well as a range of constraints for dose optimization under different risk levels.

Optimized decision support for selection of transoral robotic surgery or (chemo)radiation therapy based on posttreatment swallowing toxicity.

BACKGROUND: A primary goal in transoral robotic surgery (TORS) for oropharyngeal squamous cell cancer (OPSCC) survivors is to optimize swallowing function. However, the uncertainty in the outcomes of TORS including postoperative residual positive margin (PM) and extranodal extension (ENE), may necessitate adjuvant therapy, which may cause significant swallowing toxicity to survivors. METHODS: A secondary analysis was performed on a prospective registry data with low- to intermediate-risk human papillomavirus-related OPSCC possibly resectable by TORS. Decision trees were developed to model the uncertainties in TORS compared with definitive radiation therapy (RT) and chemoradiation therapy (CRT). Swallowing toxicities were measured by Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), MD Anderson Dysphagia Inventory (MDADI), and the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) instruments. The likelihoods of PM/ENE were varied to determine the thresholds within which each therapy remains optimal. RESULTS: Compared with RT, TORS resulted in inferior swallowing function for moderate likelihoods of PM/ENE (>60% in short term for all instruments, >75% in long term for DIGEST and MDASI) leaving RT as the optimal treatment. Compared with CRT, TORS remained the optimal therapy based on MDADI and MDASI but showed inferior swallowing outcomes based on DIGEST for moderate-to-high likelihoods of PM/ENE (>75% for short-term and >40% for long-term outcomes). CONCLUSION: In the absence of reliable estimation of postoperative PM/ENE concurrent with significant postoperative PM, the overall toxicity level in OPSCC patients undergoing TORS with adjuvant therapy may become more severe compared with patients receiving nonsurgical treatments thus advocating definitive (C)RT protocols.

Cluster-Based Toxicity Estimation of Osteoradionecrosis via Unsupervised Machine Learning: Moving Beyond Single Dose-Parameter Normal Tissue Complication Probability by Using Whole Dose-Volume Histograms for Cohort Risk Stratification.

Purpose: Given the limitations of extant models for normal tissue complication probability estimation for osteoradionecrosis (ORN) of the mandible, the purpose of this study was to enrich statistical inference by exploiting structural properties of data and provide a clinically reliable model for ORN risk evaluation through an unsupervised-learning analysis. Materials and Methods: The analysis was conducted on retrospective data of 1,259 head and neck cancer (HNC) patients treated at the University of Texas MD Anderson Cancer Center between 2005 and 2015. The (structural) clusters of mandibular dose-volume histograms (DVHs) were identified through the K-means clustering method. A soft-margin support vector machine (SVM) was used to determine the cluster borders and partition the dose-volume space. The risk of ORN for each dose-volume region was calculated based on the clinical risk factors and incidence rates. Results: The K-means clustering method identified six clusters among the DVHs. Based on the first five clusters, the dose-volume space was partitioned almost perfectly by the soft-margin SVM into distinct regions with different risk indices. The sixth cluster overlapped the others entirely; the region of this cluster was determined by its envelops. These regions and the associated risk indices provide a range of constraints for dose optimization under different risk levels. Conclusion: This study presents an unsupervised-learning analysis of a large-scale data set to evaluate the risk of mandibular ORN among HNC patients. The results provide a visual risk-assessment tool (based on the whole DVH) and a spectrum of dose constraints for radiation planning.

MR-Guided Adaptive Radiotherapy for OAR Sparing in Head and Neck Cancers.

MR-linac devices offer the potential for advancements in radiotherapy (RT) treatment of head and neck cancer (HNC) by using daily MR imaging performed at the time and setup of treatment delivery. This article aims to present a review of current adaptive RT (ART) methods on MR-Linac devices directed towards the sparing of organs at risk (OAR) and a view of future adaptive techniques seeking to improve the therapeutic ratio. This ratio expresses the relationship between the probability of tumor control and the probability of normal tissue damage and is thus an important conceptual metric of success in the sparing of OARs. Increasing spatial conformity of dose distributions to target volume and OARs is an initial step in achieving therapeutic improvements, followed by the use of imaging and clinical biomarkers to inform the clinical decision-making process in an ART paradigm. Pre-clinical and clinical findings support the incorporation of biomarkers into ART protocols and investment into further research to explore imaging biomarkers by taking advantage of the daily MR imaging workflow. A coherent understanding of this road map for RT in HNC is critical for directing future research efforts related to sparing OARs using image-guided radiotherapy (IGRT).

Efficacy of Methotrexate on Pain Severity Reduction and Improvement of Quality of Life in Patients with Moderate to Severe Knee Osteoarthritis.

BACKGROUND: Knee osteoarthritis (OA) leads to low quality of life due to pain and limitation in daily activities. Recent studies indicated that Methotrexate (MTX) could reduce pain due to its anti-inflammatory effects. OBJECTIVES: In this study, the researchers aimed at evaluating the efficacy of MTX in pain control and improvement of quality of life in patients with moderate to severe knee OA. METHODS: In this randomized clinical trial, 100 patients with moderate to severe knee OA were allocated to receive MTX (n = 50) 7.5 mg weekly to be increased to 15 mg weekly after first months or placebo (n = 50) for six months. Pain severity was measured using the numerical rating scale (NRS), so was functional status by Western Ontario and McMaster Universities Arthritis Index (WOMAC) and quality of life by SF-12 questionnaire before the treatment, and three months and six months after the intervention. The results were compared between the groups subsequently. Nine patients from the MTX group were excluded due to the use of corticosteroids during the treatment period. RESULTS: The MTX group compared to the placebo group had significant improvement in pain severity and quality of life during six months and WOMAC parameters at three and six months after the intervention. The need for NSAIDS was slightly higher in the placebo group with no significant difference (22% versus 36%, P = 0.14). The MTX adverse effects were not observed. CONCLUSIONS: Treatment of moderate to severe knee OA with MTX could reduce pain severity and improve functional status and quality of life in OA patients.

Libman-Sacks endocarditis in patients with systemic lupus erythematosus with secondary antiphospholipid syndrome.

BACKGROUND: Libman-Sacks endocarditis (LSE) is characterized by sterile lesions that commonly affect the aortic and mitral heart valves. Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) have been associated with LSE. Cardiac manifestations including LSE could be interrelated with other manifestations and early diagnosis could help in preventing further complications. CASE PRESENTATION: Here, we report three cases of LSE in SLE patients with secondary APS. All patients presented with neurological manifestations and LSE was diagnosed by Transesophageal echocardiography (TEE). All three patients were treated for the underlying disease and also received anticoagulant therapy. CONCLUSION: In all patients with SLE and secondary APS, LSE should be considered if a patient manifests any evidence of neurologic involvement.

Development of Hepatic Steatosis After Chemotherapy for Non-Hodgkin Lymphoma.

Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non-Hodgkin lymphoma (NHL). In this retrospective case-control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R-CHOP) or R-CHOP + etoposide (EPOCH-R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3- to 6-month intervals and reviewed for steatosis. Patients with de novo steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow-up 53 months), 25 (10%) developed de novo steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m2; P = 0.014) and hyperlipidemia (12% versus 2%; P = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m2 (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls (P = 0.003). Etoposide-containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; P < 0.001) despite similar baseline risk factors. Conclusion: The recovery period from NHL chemotherapy appears to be a "hot spot" for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.

The effect of Cardiac Arrhythmias Simulation Software on the nurses' learning and professional development.

INTRODUCTION: One of the important tasks of nurses in intensive care unit is interpretation of ECG. The use of training simulator is a new paradigm in the age of computers. This study was performed to evaluate the impact of cardiac arrhythmias simulator software on nurses' learning in the subspecialty Vali-Asr Hospital in 2016. METHODS: This study was conducted by quasi-experimental randomized Salomon four group design with the participation of 120 nurses in subspecialty Vali-Asr Hospital in Tehran, Iran in 2016 that were selected purposefully and allocated in 4 groups. By this design other confounding factors such as the prior information, maturation and the role of sex and age were controlled by Solomon 4 design. The valid and reliable multiple choice test tools were used to gather information; the validity of the test was approved by experts and its reliability was obtained by Cronbach's alpha coefficient 0.89. At first, the knowledge and skills of the participants were assessed by a pre-test; following the educational intervention with cardiac arrhythmias simulator software during 14 days in ICUs, the mentioned factors were measured for the two groups again by a post-test in the four groups. Data were analyzed using the two way ANOVA. The significance level was considered as p<0.05. RESULTS: Based on randomized four-group Solomon designs and our test results, using cardiac arrhythmias simulator software as an intervention was effective in the nurses' learning since a significant difference was found between pre-test and post-test in the first group (p<0.05). Also, other comparisons by ANOVA test showed that there was no interaction between pre-test and intervention in all of the three knowledge areas of cardiac arrhythmias, their treatments and their diagnosis (P>0.05). CONCLUSION: The use of software-based simulator for cardiac arrhythmias was effective in nurses' learning in light of its attractive components and interactive method. This intervention increased the knowledge of the nurses in cognitive domain of cardiac arrhythmias in addition to their diagnosis and treatment. Also, the package can be used for training in other areas such as continuing medical education.

The Efficacy of Hydration with Normal Saline Versus Hydration with Sodium Bicarbonate in the Prevention of Contrast-induced Nephropathy.

BACKGROUND: Contrast-induced acute kidney injury [contrast-induced nephropathy (CIN)] is one of the major causes of hospital-acquired acute renal failure. Volume supplementation is the most effective strategy to prevent acute renal failure caused by contrast; but the effects of sodium bicarbonate regimens are unknown in CIN prevention. The aim of this survey is to compare the efficacy of hydration with normal saline versus hydration with sodium bicarbonate in the prevention of the CIN in patients undergoing coronary angiography. MATERIALS AND METHODS: In a clinical trial, 350 patients undergoing coronary interventions were randomized into two groups: One group received normal saline and another group received sodium bicarbonate before and after infusion of the contrast. Patients in both the groups had received N-acetylcysteine. CIN was defined as relative increase in serum creatinine equal to or more than 25% of baseline or increase to 0.5 mg/dl in 48 h after the injection of the contrast. RESULTS: CIN was seen in 46 patients (13.1%) after coronary interventions. Incidence of CIN in patients receiving normal saline (19.4%) was more than in patients receiving sodium bicarbonate (6.9%) (P = 0.001). Hemodialysis was needed only in one patient who received saline normal. Relative risk to induce CIN in both groups was as 2.8 and was in the range of 1.50-5.25 with confidence interval of 95% and P = 0.001. Thus, the probability of CIN was significantly more in the usage of normal saline. CONCLUSION: This survey showed that hydration with sodium bicarbonate is superior to hydration with normal saline and has better protection effects.