Relative Efficacies of Interventions to Improve the Quality of Screening-Related Colonoscopy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND & AIMS: Significant variability exists in colonoscopy quality indicators, including adenoma detection rate (ADR). We synthesized evidence from randomized trials in a network meta-analysis on interventions to improve colonoscopy quality. METHODS: We included trials from database inceptions to September 25, 2023, of patients undergoing screening-related colonoscopy and presented efficacies of interventions within domains (periprocedural parameters, endoscopist-directed interventions, intraprocedural techniques, endoscopic technologies, distal attachment devices, and additive substances) compared to standard colonoscopy. The primary outcome was ADR. We used a Bayesian random-effects model using Markov-chain Monte Carlo simulation, with 10,000 burn-ins and 100,000 iterations. We calculated odds ratios with 95% credible intervals and present surface under the cumulative ranking (SUCRA) curves. RESULTS: We included 124 trials evaluating 37 interventions for the primary outcome. Nine interventions resulted in statistically significant improvements in ADR compared to standard colonoscopy (9-minute withdrawal time, dual observation, water exchange, i-SCAN [Pentax Ltd], linked color imaging, computer-aided detection, Endocuff [Olympus Corp], Endocuff Vision [Olympus Corp], and oral methylene blue). Dual observation (SUCRA, 0.84) and water exchange (SUCRA, 0.78) ranked highest among intraprocedural techniques; i-SCAN (SUCRA, 0.95), linked color imaging (SUCRA, 0.85), and computer-aided detection (SUCRA, 0.78) among endoscopic technologies; WingCap (A&A Medical Supply LLC) (SUCRA, 0.87) and Endocuff (SUCRA, 0.85) among distal attachment devices and oral methylene blue (SUCRA, 0.94) among additive substances. No interventions improved detection of advanced adenomas, and only narrow-band imaging improved detection of serrated lesions (odds ratio, 2.94; 95% credible interval, 1.46-6.25). CONCLUSIONS: Several interventions are effective in improving adenoma detection and overall colonoscopy quality, many of which are cost-free. These results can inform endoscopists, unit managers, and endoscopy societies on relative efficacies.

The association between neighborhood-level income and cancer stage at diagnosis and survival in Alberta.

BACKGROUND: Socioeconomic status (SES) is associated with a range of health outcomes, including cancer diagnosis and survival. However, the evidence for this association is inconsistent between countries with and without single-payer health care systems. In this study, the relationships between neighborhood-level income, cancer stage at diagnosis, and cancer-specific mortality in Alberta, Canada, were evaluated. METHODS: The Alberta Cancer Registry was used to identify all primary cancer diagnoses between 2010 and 2020. Average neighborhood income was determined by linking the Canadian census to postal codes and was categorized into quintiles on the basis of income distribution in Alberta. Multivariable multinomial logistic regression was used to model the association between income quintile and stage at diagnosis, and the Fine-Gray proportional subdistribution hazards model was used to estimate the association between SES and cancer-specific mortality. RESULTS: Out of the 143,818 patients with cancer included in the study, those in lower income quintiles were significantly more likely to be diagnosed at stage III (odds ratio [OR], 1.07; 95% CI [confidence interval], 1.06-1.09) or IV (OR, 1.12; 95% CI, 1.11-1.14) after adjusting for age and sex. Lower income quintiles also had significantly worse cancer-specific survival for breast, colorectal, liver, lung, non-Hodgkin lymphoma, oral cavity, pancreas, and prostate cancers. CONCLUSIONS: Disparities were observed in cancer outcomes across neighborhood-level income groups in Alberta, which demonstrates that health inequities by SES exist in countries with single-payer health care systems. Further research is needed to better understand the underlying causes and to develop strategies to mitigate these disparities.

Association between treatment and improvements in overall survival of patients with advanced/metastatic non-small cell lung cancer since 2011: A study in the United States, Canada, and Germany using retrospective real-world databases.

BACKGROUND: This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) in three countries between 2011 and 2020. METHODS: Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS. FINDINGS: We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months. CONCLUSIONS: Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation.

Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a common, debilitating disorder characterized by abdominal pain and disordered bowel habits. Current pharmacologic treatments often provide incomplete symptom relief and may be poorly tolerated. Furthermore, alleviation of gastrointestinal symptoms does not always translate into improved quality of life for IBS patients. Current treatment guidelines recommend brain-gut behavior therapy (BGBT) in conjunction with other IBS therapies, and, in randomized controlled trials, BGBT has been shown to improve symptoms, patient satisfaction, functioning, and quality of life. Access to BGBT is limited by lack of adequately trained gastrointestinal psychologists, patient time constraints, and cost. Furthermore, clinician knowledge that BGBT is specific, and different from psychotherapy approaches for common mental health disorders, may limit referrals even where available. This review provides an overview of the pathophysiology of IBS, disease burden, unmet therapeutic needs, evidence base of novel digital therapeutics for IBS, and guidance on the introduction and appropriateness of these interventions for patients. METHODS: We searched the literature for available published data relating to the use of novel digital therapeutics to provide cognitive behavioral therapy and gut-directed hypnotherapy in the treatment of irritable bowel syndrome. RESULTS: Clinical trial data support the development and utility of digital therapeutics designed to deliver self-guided cognitive behavioral therapy and hypnotherapy for the treatment of IBS. CONCLUSIONS: BGBTs are effective, guideline-recommended treatments for IBS. Digital therapeutic devices offer accessible, cost-effective treatment options for delivery of adjunctive BGBT for the treatment of IBS. The decision to recommend digital BGBTs should be guided by careful patient assessment that includes mental health screening and risk assessment.

Perceptions, Definitions, and Therapeutic Interventions for Occasional Constipation: A Rome Working Group Consensus Document.

BACKGROUND & AIMS: Functional constipation is the most common of the disorders of gut-brain interaction, affecting approximately 12% of the world population. Although classically considered a chronic condition, many individuals experience shorter yet repetitive bouts of constipation representing a different clinical entity. There has been increased interest in this latter disorder, which has recently been classified as occasional constipation. This Rome Foundation working group document reflects the consensus of an international team of specialists who summarized currently available research to provide a working definition of and treatment algorithm for occasional constipation. The recommendations herein are based on current evidence, accounting for gaps in the literature as well as international variance in definitions and health seeking behaviors for constipation. METHODS: The committee members reviewed the scientific literature, focusing specifically on occasional constipation, with the understanding that as a new entity, a paucity of data would be available. We used Rome IV research and clinical definitions to establish the framework for our definition of occasional constipation. Where possible, treatment recommendations were determined on the basis of the earliest extractable data from functional constipation studies, focusing on positive results within the first 2 weeks of treatment. We used the Delphi method to create consensus with 100% agreement between the authors. RESULTS: An evidence-based review of the literature resulted in the definition of occasional constipation as follows: "individuals who experience the presence of at least 1 functional constipation symptom, in the absence of alarm signs or symptoms, occurring at irregular and infrequent intervals, which is bothersome enough to induce a patient to seek medical management." Medical management whether seeking medical care or self-treatment was left to the individual's discretion, and we did not include time anchors because these thresholds require further investigation. Polyethylene glycol and stimulant laxatives are recommended as first-line interventions, whereas magnesium-containing compounds are suggested in individuals failing to respond to these therapies. There are insufficient data to make recommendations for using fiber or stool softeners. Prescription laxatives should be reserved for individuals with chronic constipation. CONCLUSIONS: Occasional constipation is a unique clinical entity characterized by infrequent but recurrent symptoms. Data are limited because consensus definitions have been lacking. Establishing a standardized definition and therapeutic recommendations provides a framework for future studies focusing on epidemiologic and symptoms-based outcomes. Further studies are needed to confirm and refine these recommendations.

Optimizing the Management Algorithm for Adults With Functional Constipation Failing a Fiber/Laxative Trial in General Gastroenterology: Cost-Effectiveness and Cost-Minimization Analysis.

INTRODUCTION: Anorectal function testing is traditionally relegated to subspecialty centers. Yet, it is an office-based procedure that appears capable of triaging care for the many patients with Rome IV functional constipation that fail empiric over-the-counter therapy in general gastroenterology, as an alternative to empirical prescription drugs. We aimed to evaluate cost-effectiveness of routine anorectal function testing in this specific population. METHODS: We performed a cost-effectiveness analysis from the patient perspective and a cost-minimization analysis from the insurer perspective to compare 3 strategies: (i) empiric prescription drugs followed by pelvic floor physical therapy (PFPT) for drug failure, (ii) empiric PFPT followed by prescription drugs for PFPT failure, or (iii) care directed by up-front anorectal function testing. Model inputs were derived from systematic reviews of prospective clinical trials, national cost data sets, and observational cohort studies of the impact of chronic constipation on health outcomes, healthcare costs, and work productivity. RESULTS: The most cost-effective strategy was upfront anorectal function testing to triage patients to appropriate therapy, in which the subset of patients without anal hypocontractility on anorectal manometry and with a balloon expulsion time of at least 6.5 seconds would be referred to PFPT. In sensitivity analysis, empiric PFPT was more cost effective than empiric prescription drugs except for situations in which the primary goal of treatment was to increase bowel movement frequency. If adopted, gastroenterologists would refer ∼17 patients per year to PFPT, supporting feasibility. DISCUSSION: Anorectal function testing seems to be an emergent technology to optimize cost-effective outcomes, overcoming testing costs by phenotyping care.

Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

INTRODUCTION: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness. METHODS: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed. RESULTS: Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was -2.66 for tenapanor vs -2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week. DISCUSSION: Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo.

Incidence, Predictors, and Outcomes of Clinically Significant Post-ERCP Bleeding: a Contemporary Multi-center Study.

BACKGROUND AIMS: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors for and outcomes following CSPEB. METHODS: We analyzed multi-center prospective ERCP data between 2018-2023 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in: hemoglobin drop ≥20 g/L or transfusion and/or endoscopy to evaluate suspected bleeding, and/or unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was employed. P-values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. RESULTS: CSPEB occurred following 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring following higher-risk interventions (sphincterotomy, sphincteroplasty, pre-cut sphincterotomy, and/or needle-knife access). CSPEB patients required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with three cases (2.3%) being fatal. P2Y12 inhibitors were held for a median of 4 days (IQR 4) prior to higher-risk ERCP. Following higher-risk interventions, P2Y12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24) and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding post sphincterotomy (OR 2.32, 1.06-4.60), but not post sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days following CSPEB (OR 12.71, 4.75-32.54). CONCLUSIONS: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher-risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.

Next Generation Weight Loss Drugs for the Prevention of Cancer?

Background: Western populations are losing the battle over healthy weight management, and excess body weight is a notable cancer risk factor at the population level. There is ongoing interest in pharmacological interventions aimed at promoting weight loss, including GLP-1 receptor agonists (GLP-1RA), which may be a useful tool to stem the rising tide of obesity-related cancers. Purpose: To investigate the potential of next generation weight loss drugs (NGWLD) like GLP-1RA in population-level chemoprevention.Research Design: We used the OncoSim microsimulation tool to estimate the population-level reductions in obesity and the potentially avoidable obesity-related cancers in Canada over the next 25 years.Results: We estimated a total of 71 281 preventable cancers by 2049, with 36 235 and 35 046 cancers prevented for females and males, respectively. Among the 327 254 total projected cancer cases in 2049, 1.3% are estimated to be preventable through intervention with NGWLD.Conclusions: Pharmacologic intervention is not the ideal solution for the obesity-related cancer crisis. However, these agents and subsequent generations provide an additional tool to rapidly reduce body weight and adiposity in populations that have been extremely challenging to reduce weight with standard diet and exercise approaches. Additional research is needed around approaches to prevent initial weight gain and maintain long-term weight loss.

Projected estimates of cancer in Canada in 2024.

BACKGROUND: Cancer surveillance data are essential to help understand where gaps exist and progress is being made in cancer control. We sought to summarize the expected impact of cancer in Canada in 2024, with projections of new cancer cases and deaths from cancer by sex and province or territory for all ages combined. METHODS: We obtained data on new cancer cases (i.e., incidence, 1984-2019) and deaths from cancer (i.e., mortality, 1984-2020) from the Canadian Cancer Registry and Canadian Vital Statistics Death Database, respectively. We projected cancer incidence and mortality counts and rates to 2024 for 23 types of cancer, overall, by sex, and by province or territory. We calculated age-standardized rates using data from the 2011 Canadian standard population. RESULTS: In 2024, the number of new cancer cases and deaths from cancer are expected to reach 247 100 and 88 100, respectively. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) are projected to decrease slightly from previous years for both males and females, with higher rates among males (ASIR 562.2 per 100 000 and ASMR 209.6 per 100 000 among males; ASIR 495.9 per 100 000 and ASMR 152.8 per 100 000 among females). The ASIRs and ASMRs of several common cancers are projected to continue to decrease (i.e., lung, colorectal, and prostate cancer), while those of several others are projected to increase (i.e., liver and intrahepatic bile duct cancer, kidney cancer, melanoma, and non-Hodgkin lymphoma). INTERPRETATION: Although the overall incidence of cancer and associated mortality are declining, new cases and deaths in Canada are expected to increase in 2024, largely because of the growing and aging population. Efforts in prevention, screening, and treatment have reduced the impact of some cancers, but these short-term projections highlight the potential effect of cancer on people and health care systems in Canada.

Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data.

BACKGROUND: Laboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta's biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them. METHODS: In our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta Dataset (SAD) and 6944 entries from the Northern Alberta Dataset (NAD). The data covers all of Alberta and is completely population-based. Our proposed framework is built around rule-based IE methods. It incorporates topics such as Syntax and Lexical analyses to achieve deterministic extraction of data from biomarker laboratory data (i.e., Epidermal Growth Factor Receptor (EGFR) test results). Lexical analysis compromises of data cleaning and pre-processing, Rich Text Format text conversion into readable plain text format, and normalization and tokenization of text. The framework then passes the text into the Syntax analysis stage which includes the rule-based method of extracting relevant data. Rule-based patterns of the test result are identified, and a Context Free Grammar then generates the rules of information extraction. Finally, the results are linked with the Alberta Cancer Registry to support real-world cancer research studies. RESULTS: Of the original 5512 entries in the SAD dataset and 5017 entries in the NAD dataset which were filtered for EGFR, the framework yielded 5129 and 3388 extracted EGFR test results from the SAD and NAD datasets, respectively. An accuracy of 97.5% was achieved on a random sample of 362 tests. CONCLUSIONS: We presented a text analysis framework to extract specific information from unstructured clinical data. Our proposed framework has shown that it can successfully extract relevant information from EGFR test results.

Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation.

BACKGROUND: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C). AIM: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity. METHODS: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12. RESULTS: At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: - 1.7 vs - 1.3; P = 0.002), reduced abdominal pain (- 1.7 vs - 1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: - 1.3 vs - 1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (- 0.9 vs - 0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03]). CONCLUSION: Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating.

A qualitative review of social media sharing and the 2022 monkeypox outbreak: did early labelling help to curb misinformation or fuel the fire?

BACKGROUND: Misinformation, defined as a claim that is false or misleading, considers information that is both shared with the intention of causing harm, and information that is false with no ill intent. Early attempts to downplay the risk of monkeypox (mpox) by singling out men who have sex with men (MSM) may have had the ill effect of stigmatising this group in discussions online. The aim of this study was to evaluate themes present on Instagram related to the 2022 mpox outbreak under #monkeypox. Specifically, this study sought to determine if the pervasive narratives surrounding the coronavirus disease 2019 (COVID-19) pandemic, particularly related to government mistrust and conspiracy, were penetrating discussions about mpox. METHODS: A total of 255 posts under #monkeypox (the top 85 posts per day, every 10days in July 2022) were collected on Instagram. A content analysis approach, which seeks to quantify themes present, was utilised to evaluate themes present in posts under #monkeypox. RESULTS: Contrary to previous research investigating public health misinformation online, the majority of posts under #monkeypox were categorised as accurate information (85.9%). Moreover, a surprising number of posts were classified as anti-misinformation (32.9%), whereby users actively worked to debunk false information being shared online related to mpox. CONCLUSIONS: We hypothesise that early labelling of the disease as one that strictly affects online MSM communities has resulted in the digital community coming together to fact-check and debunk misinformation under #monkeypox on Instagram.

Outcomes and Healthcare Utilization Among New Persistent Opioid Users and Nonopioid Users After Curative-intent Surgery for Cancer.

OBJECTIVE: The aim of the study was to compare the health outcomes and resource use of cancer patients who were new persistent opioid users with those who were not, after undergoing curative intent surgery for cancer. BACKGROUND: Little is known about long-term health outcomes (overdose, mortality) and resource utilization of new persistent opioid users among cancer patients undergoing curative-intent surgery. METHODS: This retrospective cohort study included all adults with a diagnosis of solid cancers who underwent curative-intent surgery during the study period (2011-2015) in Alberta, Canada and were opioid-naïve before surgery, with a follow-up period until December 31, 2019. The key exposure, "new persistent opioid user," was defined as a patient who was opioid-naive before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery. The primary outcome was opioid overdose that occurred within 3 years of surgery. All-cause death, noncancer caused death, and department visit (yes vs. no), and hospitalization (yes vs. no) in the follow-up periods were also included as outcomes. RESULTS: In total, 19,219 patients underwent curative intent surgery with a median follow-up of 47 months, of whom 1530 (8.0%) were identified as postoperative new persistent opioid users. In total, 101 (0.5%) patients experienced opioid overdose within 3 years of surgery. Compared with nonopioid users, new persistent opioid users experienced a higher rate of opioid overdose (OR = 2.37, 95% CI: 1.44-3.9) within 3 years of surgery. New persistent opioid use was also associated with a greater likelihood of being hospitalized (OR = 2.03, 95% CI: 1.76-2.33) and visiting an emergency room (OR = 1.83, 95% CI: 1.62-2.06) in the first year after surgery, and a higher overall (HR = 1.28, 95% CI: 1.1-1.49) and noncancer caused mortality (HR = 1.33, 95% CI: 1.12-1.58), when compared with nonopioid users. CONCLUSION: Postoperative new persistent opioid use among cancer patients undergoing curative-intent surgery is associated with subsequent opioid overdose, worse survival, and more health resource utilization.

Development and Validation of a Prognostic Risk Model for Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Risk stratification tools for patients with advanced melanoma (AM) treated with immune checkpoint inhibitors (ICI) are lacking. We identified a new prognostic model associated with overall survival (OS). PATIENTS AND METHODS: A total of 318 treatment naïve patients with AM receiving ICI were collected from a multi-centre retrospective cohort study. LASSO Cox regression identified independent prognostic factors associated with OS. Model validation was carried out on 500 iterations of bootstrapped samples. Harrel's C-index was calculated and internally validated to outline the model's discriminatory performance. External validation was carried out in 142 advanced melanoma patients receiving ICI in later lines. RESULTS: High white blood cell count (WBC), high lactate dehydrogenase (LDH), low albumin, Eastern Cooperative Oncology Group (ECOG) performance status ≥1, and the presence of liver metastases were included in the model. Patients were parsed into 3 risk groups: favorable (0-1 factors) OS of 52.9 months, intermediate (2-3 factors) OS 13.0 months, and poor (≥4 factors) OS 2.7 months. The C-index of the model from the discovery cohort was 0.69. External validation in later-lines (N = 142) of therapy demonstrated a c-index of 0.65. CONCLUSIONS: Liver metastases, low albumin, high LDH, high WBC, and ECOG≥1 can be combined into a prognostic model for AM patients treated with ICI.

Rare, Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists.

Recurrent abdominal pain is a common reason for repeated visits to outpatient clinics and emergency departments, reflecting a substantial unmet need for timely and accurate diagnosis. A lack of awareness of some of the rarer causes of recurrent abdominal pain may impede diagnosis and delay effective management. This article identifies some of the key rare but diagnosable causes that are frequently missed by gastroenterologists and provides expert recommendations to support recognition, diagnosis, and management with the ultimate aim of improving patient outcomes.

Up-Front Endoscopy Maximizes Cost-Effectiveness and Cost-Satisfaction in Uninvestigated Dyspepsia.

BACKGROUND & AIMS: Practice guidelines promote a routine noninvasive, non-endoscopic initial approach to investigating dyspepsia without alarm features in young patients, yet many patients undergo prompt upper endoscopy. We aimed to assess tradeoffs among costs, patient satisfaction, and clinical outcomes to inform discrepancy between guidelines and practice. METHODS: We constructed a decision-analytic model and performed cost-effectiveness/cost-satisfaction analysis over a 1-year time horizon on patients with uninvestigated dyspepsia without alarm features referred to gastroenterology. A RAND/UCLA expert panel informed model design. Four competing diagnostic/management strategies were evaluated: prompt endoscopy, testing for Helicobacter pylori and eradicating if present (test-and-treat), testing for H pylori and performing endoscopy if present (test-and-scope), and empiric acid suppression. Outcomes were derived from systematic reviews of clinical trials. Costs were informed by prospective observational cohort studies and national commercial/federal cost databases. Health gains were represented using quality-adjusted life years. RESULTS: From the patient perspective, costs and outcomes were similar for all strategies (maximum out-of-pocket difference of $30 and <0.01 quality-adjusted life years gained/year regardless of strategy). Prompt endoscopy maximized cost-satisfaction and health system reimbursement. Test-and-scope maximized cost-effectiveness from insurer and patient perspectives. Results remained robust on multiple one-way sensitivity analyses on model inputs and across most willingness-to-pay thresholds. CONCLUSIONS: Noninvasive management strategies appear to result in inferior cost-effectiveness and patient satisfaction outcomes compared with strategies promoting up-front endoscopy. Therefore, additional studies are needed to evaluate the drivers of patient satisfaction to facilitate inclusion in value-based healthcare transformation efforts.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Linaclotide Reduced Response Time for Irritable Bowel Syndrome With Constipation Symptoms: Analysis of 4 Randomized Controlled Trials.

INTRODUCTION: These post hoc analyses provide clinically relevant data concerning time to response for individual irritable bowel syndrome with constipation (IBS-C) symptoms after linaclotide use. METHODS: Time-to-response data were pooled from 4 randomized controlled trials. Response time for abdominal symptoms (pain, discomfort, and bloating) and complete spontaneous bowel movements (CSBMs) were analyzed using the Kaplan-Meier method; patients were categorized as early responders (≤4 weeks), late responders (>4-12 weeks), or nonresponders. RESULTS: Among 2,350 patients (1,172 placebo and 1,178 linaclotide 290 µg), >50% of patients with IBS-C who initiated linaclotide treatment experienced a decrease of ≥30% in abdominal pain, discomfort, or bloating within 3-4 weeks (median). The median time to achieving ≥3 CSBMs was 4 weeks. Although not all linaclotide-treated patients responded within 12 weeks, a late response occurred between 4 and 12 weeks in 1 in 6 patients for abdominal pain and in approximately 1 in 10 patients for CSBM frequency. Comparisons of early responders, late responders, and nonresponders for both response definitions indicated that women, Whites, and patients with less severe baseline abdominal symptoms were more likely to respond early. DISCUSSION: Although treatment responses with linaclotide occurred in >50% of patients with IBS-C within 4 weeks of treatment initiation, benefits for individual abdominal symptoms and/or CSBM frequency can still occur between 4 and 12 weeks. A lack of improvement in one symptom does not negate the possibility of response for others, highlighting the importance of discussing all symptoms with patients and not assuming treatment futility at 4 weeks.

Time spent in the sun and the risk of developing non-Hodgkin lymphoma: a Canadian cohort study.

PURPOSE: The objective was to explore the relationship of sun behavior patterns with the risk of developing non-Hodgkin lymphoma (NHL). METHODS: Sun behavior information from Alberta's Tomorrow Project, CARTaGENE, and Ontario Health Study were utilized. The relationship between time in the sun during summer months and risk of NHL was assessed using Cox proportional hazard models with age as the time scale and adjustment for confounders. Cohorts were analyzed separately and hazard ratios (HR) pooled with random effects meta-analysis. Joint effects of time in the sun and use of sun protection were examined. Patterns of exposure were explored via combinations of weekday and weekend time in the sun. RESULTS: During an average follow-up of 7.6 years, 205 NHL cases occurred among study participants (n = 79,803). Compared to < 30 min daily in the sun, we observed HRs of 0.84 (95% CI 0.55-1.28) for 30-59 min, 0.63 (95% CI 0.40-0.98) for 1-2 h, and 0.91 (95% CI 0.61-1.36) for > 2 h. There was suggestive evidence that > 2 h was protective against NHL with use of sun protection, but not without it. Compared to < 30 min daily, moderate exposure (30 min to 2 h on weekdays or weekend) was associated with a lower risk of NHL (HR 0.63, 95% CI 0.43-0.92), while intermittent (< 30 min on weekdays and > 2 h on weekends) and chronic (> 2 h daily) were not. CONCLUSION: This study provides evidence of a protective effect of moderate time spent in the sun on NHL risk.