Optimal Treatment Pathway Research Articles

Expert consensus on the optimal management of BRAFV600E-mutant metastatic colorectal cancer in the Asia-Pacific region.

The burden of colorectal cancer (CRC) is high in the Asia-Pacific region, and several countries in this region have among the highest and/or fastest growing rates of CRC in the world. A significant proportion of patients will present with or develop metastatic CRC (mCRC), and BRAFV600E-mutant mCRC represents a particularly aggressive phenotype that is less responsive to standard chemotherapies. In light of recent therapeutic advances, an Asia-Pacific expert consensus panel was convened to develop evidence-based recommendations for the diagnosis, treatment, and management of patients with BRAFV600E-mutant mCRC. The expert panel comprised nine medical oncologists from Australia, Hong Kong, Singapore, and Taiwan (the authors), who met to review current literature and develop eight consensus statements that describe the optimal management of BRAFV600E-mutant mCRC in the Asia-Pacific region. As agreed by the expert panel, the consensus statements recommend molecular testing at diagnosis to guide individualized treatment decisions, propose optimal treatment pathways according to microsatellite stability status, advocate for more frequent monitoring of BRAFV600E-mutant mCRC, and discuss local treatment strategies for oligometastatic disease. Together, these expert consensus statements are intended to optimize treatment and improve outcomes for patients with BRAFV600E-mutant mCRC in the Asia-Pacific region.

Perioperative Management and Outcomes after Endovascular Mechanical Thrombectomy in Patients with Submassive (Intermediate-Risk) Pulmonary Embolism: A Retrospective Observational Cohort Study.

Pulmonary embolism (PE) embodies a large healthcare burden globally and is the third leading cause of morbidity and mortality worldwide. Submassive (intermediate-risk) PE accounts for 40% of this burden. However, the optimal treatment pathway for this population remains complex and ill-defined. Catheter-directed interventions (CDIs) have shown promise in directly impacting morbidity and mortality while demonstrating a favorable success rate, safety profile, and decreased length of stay (LOS) in the intensive care unit and hospital. This retrospective review included 22 patients (50% female) with submassive PE who underwent mechanical thrombectomy (MT). A total of 45% had a contraindication to thrombolytics, the mean pulmonary embolism severity index was 127, 36% had saddle PE, the average decrease in mean pulmonary artery pressure (PAP) was 7.2 mmHg following MT, the average LOS was 6.9 days, the 30-day mortality rate was 9%, the major adverse event (MAE) rate was 9%, and the readmission rate was 13.6%. A total of 82% had successful removal of thrombus during MT with no major bleeding complications, intracranial hemorrhage events, or device-related deaths. Acknowledging the limitation of our small sample size, our data indicate that MT in the intermediate-high-risk submassive pulmonary embolism (PE) cohort resulted in a decreased hospital length of stay (LOS) and in-hospital mortality compared to standard anticoagulation therapy alone.

The Role of Pediatric Pharmacists in the Prevention and Treatment of Congenital Syphilis.

In recent years, rates of syphilis in adults have been on the rise resulting in an increase in the number of neonates born with congenital syphilis. National organizations including the Centers for Disease Control and Prevention as well as The US Preventative Services Task Force recommend routine testing of pregnant persons to identify and provide maternal syphilis treatment prior to delivery. Significant variability exists between states for these screenings, resulting in some pregnant persons not being diagnosed prior to delivery. The Pediatric Pharmacy Association (PPA) believes that pharmacists, along with other health care providers can help by ensuring optimal syphilis testing and treatment pathways for pregnant individuals and newborns are included in their workplaces. PPA also supports pharmacists working to increase treatment compliance by providing medication education and counseling regarding optimal treatment of syphilis infections, as well as work with state and local governments to standardize treatment recommendations.

Sequential interleukin-17 inhibitors for moderate-to-severe plaque psoriasis who have an IL-17 inhibitors failure in a resource limited country: An economic evaluation.

Biologics has been known to be effective for patients with psoriasis. However, optimal treatment pathways and their cost-effectiveness are limited in a resource-limited country. This study assessed the cost-effectiveness of different sequential biologics for moderate-to-severe plaque psoriasis. A hybrid model from a societal perspective was used. Model inputs were derived from network meta-analysis, clinical trials, and published literature. Three different sequential biologic treatments were assessed; Sequence 1; 1st Interleukin-17 (IL-17) inhibitor (secukinumab) followed by 2nd IL-17 inhibitors (ixekizumab or brodalumab), then 3rd IL-23 inhibitor (guselkumab), Sequence 2; ixekizumab followed by secukinumab or brodalumab, then guselkumab, and Sequence 3; brodalumab followed by ixekizumab or secukinumab, then guselkumab. Methotrexate or ciclosporin was used as standard of care (SoC). All three different sequential biologic therapies could gain total quality-adjusted life year (QALY), but they had higher cost than SoC. Sequence 1 had the lowest incremental cost-effectiveness ratio (ICER) compared to SoC at 621,373 THB/QALY (19,449 $/QALY). ICER for Sequence 2 was 957,258 THB/QALY (29,962 $/QALY), while that for Sequence 3 was 1,332,262 THB/QALY (41,700 $/QALY). Fully incremental analysis indicated that Sequence 3 was dominated by Sequence 1 and Sequence 2. ICER for Sequence 2 was 7,206,104 THB/QALY (225,551 $/QALY) when compared to Sequence 1. At the current willingness-to-pay of 160,000 THB/QALY, no sequential IL-17 inhibitor was cost-effective compared to SoC. Secukinumab followed by ixekizumab or brodalumab then guselkumab (Sequence 1) may be the most appropriate option compared with other treatments.

A Comparison between Open and Minimally Invasive Right Hemicolectomies in Patients with Locally Advanced UICC Stage III Colon Cancer: A Protocol for a Systematic Review and an Individual Patient Data Meta-Analysis

Despite the development of new technologies and multimodal therapies, improving the prognosis of patients with UICC stage III right colon adenocarcinoma remains challenging. Several randomized controlled trials have shown the oncological non-inferiority of minimally invasive surgery compared to open surgery for colon cancer patients. However, for UICC stage III patients, carrying the highest risk for local recurrence and the worst survival, the evidence remains inconclusive. The aim of this systematic review and individual patient data meta-analysis is to improve the scarce evidence regarding minimally invasive surgery for this subgroup of patients. Data from adult patients with pathologically UICC stage III right adenocarcinoma of the colon will be included. The intervention to be assessed is the minimally invasive right hemicolectomy in comparison with the open procedure. The primary outcome will be the 5-year overall survival. Secondary outcomes will include further long-term outcomes, such as disease-free survival, short term, and histological outcomes. Only randomized controlled trials and quasi-randomized controlled clinical trials will be included. The literature search will be conducted in the following databases: PubMed, CINAHL, Cochrane Trials, ClinicalTrials.gov, and Web of Science. The review will be performed using the Cochrane methodology including GRADE tools. The findings of this meta-analysis will be important for choosing optimal treatment pathways and tailoring of surgical therapy in patients with locally advanced UICC stage III right colon cancer.

“We usually see a lot of delay in terms of coming for or seeking care”: an expert consultation on COVID testing and care pathways in seven low- and middle-income countries

BackgroundRapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023.MethodsWe organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses.ResultsParticipants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at ‘face value’ by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab.ConclusionsTesting does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.

OA10 Pregnancy-associated osteoporosis - a rare subset of bone disease

OA10 Pregnancy-associated osteoporosis - a rare subset of bone disease

Shared decision making in elderly patients with kidney failure.

'Elderly' is most commonly defined as an individual aged 65years or older. However, this definition fails to account for the differences in genetics, lifestyle and overall health that contribute to significant heterogeneity among the elderly beyond chronological age. As the world population continues to age, the prevalence of chronic diseases, including chronic kidney disease (CKD), is increasing and CKD frequently progresses to kidney failure. Moreover, frailty represents a multidimensional clinical entity highly prevalent in this population, which needs to be adequately assessed to inform and support medical decisions. Selecting the optimal treatment pathway for the elderly and frail kidney failure population, be it haemodialysis, peritoneal dialysis or conservative kidney management, is complex because of the presence of comorbidities associated with low survival rates and impaired quality of life. Management of these patients should involve a multidisciplinary approach including doctors from various specialties, nurses, psychologists, dieticians and physiotherapists. Studies are mostly retrospective and observational, lacking adjustment for confounders or addressing selection and indication biases, making it difficult to use these data to guide treatment decisions. Throughout this review we discuss the difficulty of making a one-size-fits-all recommendation for the clinical needs of older patients with kidney failure. We advocate that a research agenda for optimization of the critical issues we present in this review be implemented. We recommend prospective studies that address these issues, and systematic reviews incorporating the complementary evidence of both observational and interventional studies. Furthermore, we strongly support a shared decision-making process matching evidence with patient preferences to ensure that individualized choices are made regarding dialysis vs conservative kidney management, dialysis modality and optimal vascular access.

Hypoplastic Left Heart Syndrome With Low Birth Weight or Prematurity: What Is the Optimal Approach?

BackgroundHypoplastic left heart syndrome with low birth weight or prematurity comprises a high-risk population with no optimal treatment pathway. Using the Pediatric Health Information System, we compared management approaches across the United States. MethodsWe analyzed neonates (≤30 days) with birth weight <2500 grams or gestational age <36 weeks between 2012 and 2021. Four strategies were identified: Norwood procedure, ductus arteriosus stent + pulmonary artery banding, pulmonary artery banding + prostaglandin infusion, or comfort care. Outcomes included hospital survival, discharge disposition, staged palliation completion, and 1-year transplant-free survival. ResultsOf 383 infants identified, 36.4% (n = 134) received comfort care, 43.9% (n = 165) Norwood, 12.4% (n = 49) ductal stent + pulmonary artery bands, and 8.8% (n = 34) pulmonary artery bands + prostaglandins. Neonates receiving comfort care had the lowest gestational age (35 weeks; interquartile range [IQR], 31.5-37 weeks) and birth weight (2.0 kg; IQR, 1.5-2.3 kg); 24.6% (33 of 134) had chromosomal anomalies. Infants undergoing primary Norwood had the highest birth weight (2.4 kg; IQR, 2.2-2.5 kg) and gestational age (37 weeks; IQR, 35-38 weeks). Glenn palliation was performed in 66.1% (109 of 165) compared with ductal stent + pulmonary artery band in 18.4% (9 of 49) and pulmonary artery band + prostaglandins in 35.3% (12 of 34). Only 11.3% (6 of 53) born <2 kg survived to 1 year, all after Norwood. Primary Norwood yielded higher hospital and 1-year transplant-free survival than hybrid strategies. ConclusionsComfort care is routinely provided, particularly for infants with low birth weight, gestational age, or chromosomal anomalies. Primary Norwood offered the lowest hospital and 1-year mortality and highest palliation completion rates; birth weight was the most important factor determining 1-year survival.

A ‘one-stop-shop’ point-of-care hepatitis C RNA testing intervention to enhance treatment uptake in a reception prison: The PIVOT study

Prisons are key venues for scaling-up hepatitis C virus (HCV) testing and treatment. Complex clinical pathways and frequent movements of people in prison remain barriers to HCV care. This study evaluated the impact of a 'one-stop-shop' point-of-care HCV RNA testing intervention on treatment uptake compared with standard of care among people recently incarcerated in Australia. PIVOT was a prospective, non-concurrent, controlled study comparing HCV treatment uptake during 'standard of care' (n= 239; November 2019-May 2020) and a 'one-stop-shop' intervention (n= 301; June 2020-April 2021) in one reception prison in Australia. The primary endpoint was uptake of direct-acting antiviral treatment at 12 weeks from enrolment. Secondary outcomes included the time taken from enrolment to each stage in the care cascade. A total of 540 male participants were enrolled. Median age (29 vs. 28 years) and history of injecting drug use (48% vs. 42%) were similar between standard of care and intervention phases. Among people diagnosed with current HCV infection (n= 18/63 in the standard of care phase vs. n= 30/298 in the intervention phase), the proportion initiating direct-acting antiviral treatment within 12 weeks from enrolment in the intervention phase was higher (93% [95% CI 0.78-0.99] vs. 22% [95% CI 0.64-0.48]; p <0.001), and the median time to treatment initiation was shorter (6 days [IQR 5-7] vs. 99 days [IQR 57-127]; p <0.001) compared to standard of care. The 'one-stop-shop' intervention enhanced treatment uptake and reduced time to treatment initiation among people recently incarcerated in Australia, thereby overcoming key barriers to treatment scale-up in the prison sector. This study provides important insights for policymakers regarding optimal HCV testing and treatment pathways for people newly incarcerated in prisons. The findings will improve health outcomes in people in prison with chronic HCV infection by increasing testing and treatment, thereby reducing infections, liver-related morbidity/mortality, and comorbidities. The findings will change clinical practice, clinical guidelines, and international guidance, and will inform future research and national and regional strategies, in particular regarding point-of-care testing, which is being rapidly scaled-up in various settings globally. The economic impact will likely include health budget savings resulting from reduced negative health outcomes relating to HCV, and health system efficiencies resulting from the introduction of simplified models of care. This study is registered at Clinicaltrials.gov (NCT04809246).

Ontology-aware Prescription Recommendation in Treatment Pathways Using Multi-evidence Healthcare Data

For care of chronic diseases (e.g., depression, diabetes, hypertension), it is critical to identify effective treatment pathways that aim to promptly update the medication following the change of patient state and disease progression. This task is challenging because the optimal treatment pathway for each patient needs to be personalized due to the significant heterogeneity among individuals. Therefore, it is naturally promising to investigate how to use the abundant electronic health records to recommend effective and safe prescriptions. However, prescription recommendation needs to consider multiple aspects of life-critical evidence, such as the information relevance in terms of medical concepts, the health condition in terms of diagnosis history, and the further constraint in terms of side information (e.g., patient demographics and drug side effects). To this end, in this article, we propose a novel prescription recommendation framework named OntoPath to predict the next drug in disease treatment pathways, by building an ontology-aware hierarchical-attention model that integrates multiple medical evidence from domain knowledge guidance, medical history profiling, and side information utilization. Specifically, our method can be characterized from three aspects: (1) by incorporating the longitudinal diagnosis history, we enrich the profiling of patients in terms of comprehensive health conditions, which can largely influence a drug’s outcome on individual patients; (2) using the hierarchical disease and drug ontology structures, we are able to model the domain-specific relevance between patients and drugs at multiple levels of granularity and achieve in-depth collaborative filtering; (3) we introduce a pre-training stage to enhance the discriminativeness of network representations, which helps us obtain a premium model initialization to further boost the final recommendation training. We perform extensive experiments on a large-scale depression cohort with over 37,000 patients from a real-world medical claims database. The quantitative and qualitative results demonstrate the effectiveness of OntoPath through the consistent outperformance over state-of-the-art prescription recommendation baselines and the interpretation of model mechanism in case studies.

Optimal Treatment Pathway for Diabetic Polyneuropathy

Optimal Treatment Pathway for Diabetic Polyneuropathy

Assessing the value of bypassing agent therapy used prophylactic versus on-demand, during immune tolerance induction for treatment of inhibitors: a retrospective chart review

BackgroundHaemophilia A is a bleeding disorder caused by deficiency of coagulation factor VIII (FVIII) which leads to severe and repeated bleedings. There is a need to understand the optimal treatment pathway for FVIII inhibitors with the use of immune tolerance induction (ITI) and the role of haemostatic ‘bypassing’ agents (BPA) on-demand (OD) or prophylactically (Px). The aim of this study was to gain a better understanding of the real-world use of BPA therapy administered prophylactically or on-demand concomitant with ITI, for the treatment of an inhibitor to FVIII replacement therapy in patients with severe haemophilia A.MethodsRetrospective observational data were used to capture disease management information for patients who were aged 16 or under and had received ITI and BPA treatment for their most recent inhibitor from Jan-2015 to Jan-2019, for 47 patients in the UK and Germany. Descriptive comparisons of the clinical effectiveness and resource utilisation of Px and OD BPA therapy during ITI were conducted.ResultsDuring ITI and BPA treatment, for an inhibitor, bleeding events averaged 1.5 and 1.2 for Px and OD treatment respectively. Compared to only BPA therapy we see 3.4 and 1.4 bleeding events for Px and OD respectively during an inhibitor.ConclusionBaseline disease characteristics differed between BPA therapy cohorts and this resulted in higher clinical effectiveness of ITI treatment alongside BPA Px than BPA OD during an inhibitor.

Management of left-sided malignant colorectal obstructions with curative intent: a network meta-analysis.

Several management options exist for colonic decompression in the setting of malignant large bowel obstruction, including oncologic resection, surgical diversion, and SEMS as a bridge-to-surgery. Consensus has yet to be reached on optimal treatment pathways. The aim of the present study was to perform a network meta-analysis comparing short-term postoperative morbidity and long-term oncologic outcomes between oncologic resection, surgical diversion, and self-expanding metal stents (SEMS) in left-sided malignant colorectal obstruction with curative intent. Medline, Embase, and CENTRAL were systematically searched. Articles were included if they compared two or more of the following in patients presenting with curative left-sided malignant colorectal obstruction: (1) emergent oncologic resection; (2) surgical diversion; and/or (3) SEMS. The primary outcome was overall 90-day postoperative morbidity. Pairwise meta-analyses were performed with inverse variance random effects. Random-effect Bayesian network meta-analysis was performed. From 1277 citations, 53 studies with 9493 patients undergoing urgent oncologic resection, 1273 patients undergoing surgical diversion, and 2548 patients undergoing SEMS were included. Network meta-analysis demonstrated a significant improvement in 90-day postoperative morbidity in patients undergoing SEMS compared to urgent oncologic resection (OR0.34, 95%CrI0.01-0.98). Insufficient RCT data pertaining to overall survival (OS) precluded network meta-analysis. Pairwise meta-analysis demonstrated decreased five-year OS for patients undergoing urgent oncologic resection compared to surgical diversion (OR0.44, 95%CI0.28-0.71, p < 0.01). Bridge-to-surgery interventions may offer short- and long-term benefits compared to urgent oncologic resection for malignant colorectal obstruction and should be increasingly considered in this patient population. Further prospective study comparing surgical diversion and SEMS is needed.

Abstract P6-04-05: A fully automatic artificial intelligence system for accurate and reproducible HER2 IHC scoring in breast cancer

Abstract Objective: Tumor HER2 expression is a key prognostic and treatment influencing factor in breast cancer. As with all immunohistochemistry (IHC) staining, visual interpretation of HER2 expression is subjective, which leads to intra- and inter-pathologist variability. Recent findings on the efficacy of HER2-targeted therapy on HER2-low patients raise the need for accurate and reproducible scoring. We developed a fully automated, artificial intelligence (AI) -based algorithm for HER2 scoring. The algorithm was based on ASCO/CAP 2018 guidelines and validated against rigorous ground truth (GT) established by multiple blinded expert pathologists. Methods: Algorithm development: We developed a solution that employs two steps: The first step consists of an ensemble of Deep Learning networks that process tissue regions and classify them as various tissue classes: Invasive cancer, Ductal Carcinoma In Situ (DCIS) and other morphologies. These networks were trained on slides that were automatically labeled by a separate AI system that analyzed the corresponding H&amp;E slides and projected its findings to the HER2 IHC slides using a registration algorithm. To further enrich the training set, especially with rare and difficult cases, a team of 8 expert pathologists manually marked tissue areas and assigned them to one of the tissue classes. In total, the training set consisted of 6,400 manual annotations and 1,300 automatically-annotated slides, both collected from 9 laboratories and scanned using 3 different scanners. The second step is an ensemble of Object Detection networks that process only the regions classified as invasive cancer, detect the tumor cells within them, and classify their staining pattern (e.g., Not stained, Moderate incomplete, etc.). Finally, the detected cells are counted, and the ASCO/CAP guidelines are applied to derive the slide-level HER2 score. Validation: The validation set was comprised of 453 HER2 slides stained using the VENTANA anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody as per manufacturer’s instructions. HER2 slides included biopsies and excisions with different breast cancer diagnoses (e.g., Infiltrating Ductal Carcinoma (IDC), Infiltrating Lobular Carcinoma (ILC), rare invasive subtypes, with and without DCIS) from 3 different laboratories. Ground truth was established by the consensus scores of a panel of 3 pathologists, who scored HER2 according to the guidelines without additional clinical considerations, such as scoring borderline 1+/2+ cases as 2+ to have additional tests performed. Results: The algorithm showed very high performance for detecting invasive cancer in HER2 tissue sections, with AUC of 0.967 (measured on 4-fold Cross-Validation classifying invasive vs. other regional classes). The algorithm demonstrated an overall accuracy of 80.3% for the HER2 scores when compared to the GT. When using different cutoffs for binary classification the resulting performance was: for 0 vs 1+/2+/3+ Kappa was 0.800; 0/1+ vs 2+/3+ Kappa was 0.728; for 0/1+/2+ vs 3+ Kappa was 0.954. The Quadratic Kappa between the AI score and the GT was 0.898, which is considered almost perfect. The performance of the AI was similar across the different laboratories and diagnoses(e.g. IDC, ILC). Conclusion: This study reports the successful development and independent validation of a fully automatic AI-based solution for accurate HER2 scoring in breast cancer. AI solutions, such as the one reported here, could be used as decision-support tools for pathologists in routine clinical practice, enhancing the reproducibility and consistency of HER2 scoring, thus enabling optimal treatment pathways and better patient outcomes. Accurate and automatic IHC scoring solutions can also contribute to the development of new prognostic, predictive and companion diagnostic tools. Citation Format: Yuval Globerson, Lilach Bien, Jonathan Harel, Giuseppe Mallel, Geraldine Sebag, Michel Vandenberghe, Craig Barker, Tsuyoshi Matsuo, Charo Garrido, Judith Sandbank, Chaim Linhart. A fully automatic artificial intelligence system for accurate and reproducible HER2 IHC scoring in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-05.

Helicobacter pylori World Gastroenterology Organization Global Guideline

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

Combining Molecular Subtypes with Multivariable Clinical Models Has the Potential to Improve Prediction of Treatment Outcomes in Prostate Cancer at Diagnosis.

Clinical management of prostate cancer is challenging because of its highly variable natural history and so there is a need for improved predictors of outcome in non-metastatic men at the time of diagnosis. In this study we calculated the model score from the leading clinical multivariable model, PREDICT prostate, and the poor prognosis DESNT molecular subtype, in a combined expression and clinical dataset that were taken from malignant tissue at prostatectomy (n = 359). Both PREDICT score (p < 0.0001, IQR HR = 1.59) and DESNT score (p < 0.0001, IQR HR = 2.08) were significant predictors for time to biochemical recurrence. A joint model combining the continuous PREDICT and DESNT score (p < 0.0001, IQR HR = 1.53 and 1.79, respectively) produced a significantly improved predictor than either model alone (p < 0.001). An increased probability of mortality after diagnosis, as estimated by PREDICT, was characterised by upregulation of cell-cycle related pathways and the downregulation of metabolism and cholesterol biosynthesis. The DESNT molecular subtype has distinct biological characteristics to those associated with the PREDICT model. We conclude that the inclusion of biological information alongside current clinical prognostic tools has the potential to improve the ability to choose the optimal treatment pathway for a patient.

Estimating prevalence and characteristics of statin intolerance among high and very high cardiovascular risk patients in Germany between 2017–2020

Abstract Background Statins remain the backbone of lipid management. Nevertheless, the degree to which statins can be used and dosed in clinical practice remains a great challenge, also due to statin intolerance (SI). The lack of widely accepted SI definition leads to poor understanding of the condition and SI patient profile Purpose To estimate the current SI prevalence and understand better the patient characteristics, using machine learning techniques Methods Retrospective cohort study, based on representative sample of electronic patient records from outpatient setting in Germany. Patients were included if they had high CV risk, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia (HC), between 2017 and 2020. Patients were categorized as having “absolute” (history of SI events and permanent statin discontinuation) or “partial” (history of SI events while treated with statins) SI. Machine learning techniques were utilized to calibrate the prevalence estimates and to identify patient clusters. Estimates of SI prevalence were derived based on different rules and confidence levels (high, moderate and low). The low confidence estimates contain the most uncertainty in identifying SI Results The study population consisted of 292,603 patients (57.3% aged &amp;gt;70 years; 55.6% male). Of these, ∼24% had high CV risk, ∼56% had ASCVD, and ∼20% had HC. After deploying machine learning, the SI identification improved by ∼27% in absolute SI and by ∼57% in partial SI patients, resulting in a maximum estimate of 12.5% SI with high/moderate confidence and further 11.8% with low confidence (absolute SI 15.8%, partial SI 8.5%). The low confidence group may contain patients with insufficient statin treatment due to reasons other than SI (e.g. clinical inertia). Statistically significant risk factors for SI were hypothyroidism, vitamin D deficiency, liver and chronic kidney disease. Cramps, muscle spasms, myalgia and myopathy were the most common statin associated muscle symptoms (SAMS) observed in the SI population. Atorvastatin 40mg was the most frequently down-titrated statin, while simvastatin to atorvastatin was the most predominant class switch in SI patients. Machine learning techniques applied on high confidence SI patients characteristics and the most commonly observed cluster for patients over 60 years showed predominant musculoskeletal disorders, concomitant high SAMS incidence and high use of multiple statins. In males under 60 years, depression and somatoform disorders along with musculoskeletal disorders, pain, and gastric events were common, while females under 60 years had predominant depressive episodes, along with musculoskeletal, mental, and metabolic disorders Conclusion Addressing the complexity in defining SI using advanced analytics, this study provides prevalence estimates and describes distinct patients clusters that may inform diagnosis and optimal treatment pathways for SI patients in Germany Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH

Estimating prevalence and characteristics of statin intolerance among high and very high cardiovascular risk patients in Germany between 2017–2020

Abstract Background Statins remain the backbone of lipid management. Nevertheless, the degree to which statins can be used and dosed in clinical practice remains a great challenge, also due to statin intolerance (SI). The lack of widely accepted SI definition leads to poor understanding of the condition and SI patient profile Purpose To estimate the current SI prevalence and understand better the patient characteristics, using machine learning techniques Methods Retrospective cohort study, based on representative sample of electronic patient records from outpatient setting in Germany. Patients were included if they had high CV risk, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia (HC), between 2017 and 2020. Patients were categorized as having “absolute” (history of SI events and permanent statin discontinuation) or “partial” (history of SI events while treated with statins) SI. Machine learning techniques were utilized to calibrate the prevalence estimates and to identify patient clusters. Estimates of SI prevalence were derived based on different rules and confidence levels (high, moderate and low). The low confidence estimates contain the most uncertainty in identifying SI Results The study population consisted of 292,603 patients (57.3% aged &amp;gt;70 years; 55.6% male). Of these, ∼24% had high CV risk, ∼56% had ASCVD, and ∼20% had HC. After deploying machine learning, the SI identification improved by ∼27% in absolute SI and by ∼57% in partial SI patients, resulting in a maximum estimate of 12.5% SI with high/moderate confidence and further 11.8% with low confidence (absolute SI 15.8%, partial SI 8.5%). The low confidence group may contain patients with insufficient statin treatment due to reasons other than SI (e.g. clinical inertia). Statistically significant risk factors for SI were hypothyroidism, vitamin D deficiency, liver and chronic kidney disease. Cramps, muscle spasms, myalgia and myopathy were the most common statin associated muscle symptoms (SAMS) observed in the SI population. Atorvastatin 40mg was the most frequently down-titrated statin, while simvastatin to atorvastatin was the most predominant class switch in SI patients. Machine learning techniques applied on high confidence SI patients characteristics and the most commonly observed cluster for patients over 60 years showed predominant musculoskeletal disorders, concomitant high SAMS incidence and high use of multiple statins. In males under 60 years, depression and somatoform disorders along with musculoskeletal disorders, pain, and gastric events were common, while females under 60 years had predominant depressive episodes, along with musculoskeletal, mental, and metabolic disorders Conclusion Addressing the complexity in defining SI using advanced analytics, this study provides prevalence estimates and describes distinct patients clusters that may inform diagnosis and optimal treatment pathways for SI patients in Germany Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH

Real-World Effectiveness of Newly Initiated Systemic Therapy for Atopic Dermatitis in the United States: A Claims Database Analysis

IntroductionAtopic dermatitis (AD) is associated with significant quality-of-life and economic burdens. Real-world evidence is needed to identify optimal treatment pathways for AD. Here we evaluate real-world effectiveness of systemic therapies for moderate-to-severe AD in the USA.MethodsData (September 2016 to December 2019) were from the IQVIA Health Plan Claims data set (IQVIA, Danbury, CT) from patients aged 12 years or older with AD (ICD-9/10-CM, 691.8/L20.x) initiating a systemic immunosuppressive (SIS) agent (methotrexate, cyclosporine, mycophenolate, or azathioprine) or dupilumab and continuously enrolled for at least 6 months before and after the index date. Indicators of non-response (i.e., adding on/switching systemic therapy, AD-related inpatient/emergency room visits, or incident staphylococcal/streptococcal skin infection) and predictors of non-response were evaluated. Descriptive statistics and Kaplan–Meier rates and times were obtained; Cox regression models were used.ResultsIn 3249 patients, 45.4% exhibited at least one indicator of non-response, with median time to non-response being longer for dupilumab than for any SIS therapy (27.0 vs 4.0–7.7 months, respectively). Key non-response predictors were age, geographic region, and baseline number of annual AD-related medical visits.ConclusionNon-response was common in patients with AD who required systemic treatment, and non-response indicators occurred significantly more frequently with SIS treatment than with dupilumab treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02197-z.