Conversion of Failed J-Pouch to Kock Pouch: Indications, Contraindications, and Outcomes.

BACKGROUND: The IPAA has been successful in restoring intestinal continuity and preserving continence in the majority of patients requiring a proctocolectomy. However, a subset of individuals experience significant complications that might result in pouch failure. The conversion of the J-pouch to a continent ileostomy pouch represents a significant surgical procedure. In this article, we discuss the indications and contraindications, present the technical principles applied for the conversion, and describe the outcomes of such conversion in the literature. OBJECTIVE: The main objective during the conversion of the J-pouch to a continent ileostomy is the creation of a sufficiently sized reservoir with a high-quality valve mechanism while preserving as much small bowel as possible. CONCLUSIONS: The conversion of the J-pouch to a continent ileostomy represents a significant surgical procedure. When performed in centers of expertise, it can be a good option for patients who otherwise will require an end ileostomy. Indications for conversion include most cases of J-pouch failure, with a few important exceptions. See video from symposium .

Adjusted Residuals for Evaluating Conditional Independence in IRT Models for Multistage Adaptive Testing.

The key assumption of conditional independence of item responses given latent ability in item response theory (IRT) models is addressed for multistage adaptive testing (MST) designs. Routing decisions in MST designs can cause patterns in the data that are not accounted for by the IRT model. This phenomenon relates to quasi-independence in log-linear models for incomplete contingency tables and impacts certain types of statistical inference based on assumptions on observed and missing data. We demonstrate that generalized residuals for item pair frequencies under IRT models as discussed by Haberman and Sinharay (J Am Stat Assoc 108:1435-1444, 2013. https://doi.org/10.1080/01621459.2013.835660 ) are inappropriate for MST data without adjustments. The adjustments are dependent on the MST design, and can quickly become nontrivial as the complexity of the routing increases. However, the adjusted residuals are found to have satisfactory Type I errors in a simulation and illustrated by an application to real MST data from the Programme for International Student Assessment (PISA). Implications and suggestions for statistical inference with MST designs are discussed.

Two decades of surgical randomized controlled trials: worldwide trends in volume and methodological quality.

BACKGROUND: RCTs are essential in guiding clinical decision-making but are difficult to perform, especially in surgery. This review assessed the trend in volume and methodological quality of published surgical RCTs over two decades. METHODS: PubMed was searched systematically for surgical RCTs published in 1999, 2009, and 2019. The primary outcomes were volume of trials and RCTs with a low risk of bias. Secondary outcomes were clinical, geographical, and funding characteristics. RESULTS: Some 1188 surgical RCTs were identified, of which 300 were published in 1999, 450 in 2009, and 438 in 2019. The most common subspecialty in 2019 was gastrointestinal surgery (50.7 per cent). The volume of surgical RCTs increased mostly in Asia (61, 159, and 199 trials), especially in China (7, 40, and 81). In 2019, countries with the highest relative volume of published surgical RCTs were Finland and the Netherlands. Between 2009 and 2019, the proportion of RCTs with a low risk of bias increased from 14.7 to 22.1 per cent (P = 0.004). In 2019, the proportion of trials with a low risk of bias was highest in Europe (30.5 per cent), with the UK and the Netherlands as leaders in this respect. CONCLUSION: The volume of published surgical RCTs worldwide remained stable in the past decade but their methodological quality improved. Considerable geographical shifts were observed, with Asia and especially China leading in terms of volume. Individual European countries are leading in their relative volume and methodological quality of surgical RCTs.

An RCT is a form of research in which patients are divided randomly into two or more treatment groups to allow a fair and unbiased comparison of both treatments. RCTs are essential in guiding clinical decision-making, but are difficult to perform, especially in surgery. This review assessed the trend in volume and quality of published surgical RCTs over two decades. Surgical RCTs published in 1999, 2009, and 2019 were identified. The main outcome measures were volume of RCTs and trials with a low risk of bias. Different forms of bias can occur when research results are influenced by external factors. Some 1188 surgical RCTs were identified, of which 300 were published in 1999, 450 in 2009, and 438 in 2019. The volume of surgical RCTs published in these years increased mostly in Asia (61, 159, and 199 RCTs), especially in China (7, 40, and 81). In 2019, the countries with highest relative volume of published surgical RCTs were Finland and the Netherlands. Between 2009 and 2019, the proportion of RCTs with a low risk of bias increased from 14.7 to 22.1 per cent (P = 0.004). In 2019, the proportion of trials with a low risk of bias was highest in Europe (30.5 per cent), with the UK and the Netherlands as leaders in this respect. The volume of published surgical RCTs worldwide remained stable in the past decade but their methodological quality improved. Considerable geographical shifts were observed, with Asia and especially China leading in terms of volume. Individual European countries are leading in their relative volume and methodological quality of surgical RCTs.

"Examining the Effects of Mindfulness Training on Stress and Anxiety in Sport"

The study aims to determine if stress and anxiety reduction techniques may enhance sports performance. We will do a complete assessment of earlier research on mindfulness training and sporting performance to answer this issue. This research study is based on primary data to determine whether the research study used smart PLS Software and generated informative results. The research examines how mindfulness affects stress, anxiety, and attention and how these elements affect athletic performance. We will also examine how stress and anxiety affect athletes' performance and how mindfulness training may help athletes better control these emotions. Our ultimate objective is to offer insightful analysis and suggestions to coaches and athletes who want to improve their performance via mindfulness training. Overall result found that mindfulness training has the potential to significantly impact players' physical, mental, and athletic performance. To assure widespread acceptance and success, more study is required to examine the obstacles to introducing mindfulness training in sports teams and how these obstacles might be removed. Athletes and coaches can enhance performance by integrating mindfulness training and gaining insightful information about an athlete's well-being.(AU)

Temporal trends in the incidence of malignant and nonmalignant primary brain and central nervous system tumors by the method of diagnosis in England, 1993-2017.

BACKGROUND: Several studies report increases in the incidences of primary central nervous system (CNS) tumors. The reasons for this are unclear. METHODS: Data on all 188 340 individuals diagnosed with a primary CNS tumor in England (1993-2017) were obtained from the National Cancer Registration and Analysis Service. Data on all computerized tomography (CT) head and magnetic resonance imaging (MRI) brain scans in England (2013-2017) were obtained from the National Health Service Digital. Age-sex-standardized annual incidence rates per 100 000 population (ASR) were calculated by calendar year, tumor behavior, tumor location, and method of diagnosis. Temporal trends were quantified using average annual percent change (AAPC). RESULTS: The ASR for all CNS tumors increased from 13.0 in 1993 to 18.6 in 2017 (AAPC: +1.5%, 95% CI: 1.3, 1.7). The ASR for malignant tumors (52% overall) remained stable (AAPC: +0.5%, 95% CI: -0.2, 1.3), while benign tumors (37% overall) increased (AAPC: +2.6%, 95% CI: 1.2, 4.0). Among the 66% of benign tumors that were microscopically confirmed, the ASR increased modestly (AAPC: +1.3%, 95% CI: 0.5, 2.1). However, among the 25% of benign tumors that were radiographically confirmed, the ASR increased substantially (AAPC: 10.2%, 95% CI: 7.9, 12.5), principally driven by large increases in those who are aged 65+ years. The rate of CT head scans in Accident & Emergency (A&E) increased during 2013-2017, with especially large increases in 65-84 and 85+-year-olds (AAPCs: +18.4% and +22.5%). CONCLUSIONS: Increases in CNS tumor incidence in England are largely attributable to the greater detection of benign tumors. This could be the result of the increasing use of neuroimaging, particularly CT head scans in A&E in people who are aged 65+ years.

External validation and recalibration of an incidental meningioma prognostic model - IMPACT: protocol for an international multicentre retrospective cohort study.

INTRODUCTION: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. METHODS AND ANALYSIS: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. ETHICS AND DISSEMINATION: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media.

A Classification Algorithm for Types of Diabetes in Chronic Pancreatitis Using Epidemiological Characteristics: Outcome of a Longitudinal Cohort Study.

OBJECTIVES: We developed an epidemiological algorithm to classify types of diabetes mellitus (DM) in chronic pancreatitis (CP), and applied it to a nationwide prospective longitudinal cohort of CP patients. METHODS: Patients with definite CP (M-ANNHEIM criteria) were classified as having DM types 1, 2, or 3c, or no DM using an algorithm based on epidemiological characteristics: DM onset in relation to age, CP onset, exocrine insufficiency. Variables associated with development of DM were identified. RESULTS: Of 1130 included patients with CP between 2011 and 2018, 368 patients (33%) had DM at inclusion. Among patients with DM, 11 were classified as having type 1 (3%), 159 as type 2 (43%), and 191 as type 3c (52%). Patients with DM type 3c had longer duration of CP, more severe pain and lower physical quality of life. During longitudinal follow-up of median 47 months, 120 (20%) patients developed DM, of which 99 patients were classified as type 3c. This was independently associated with pancreatic endoscopy and surgery. CONCLUSIONS: The described algorithm based on epidemiological characteristics can help to classify types of DM in patients with CP. Diabetes mellitus type 3c is associated with longer duration of CP and more severe CP sequelae.

Pain patterns in chronic pancreatitis: a nationwide longitudinal cohort study.

OBJECTIVE: Pain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing, we studied pain patterns in a prospective longitudinal nationwide study. DESIGN: 1131 patients with chronic pancreatitis (fulfilling M-ANNHEIM criteria) were included between 2011 and 2018 in 30 Dutch hospitals. Patients with continuous or intermittent pain were compared for demographics, pain characteristics, quality of life (Short-Form 36), imaging findings, disease duration and treatment. Alternation of pain pattern and associated variables were longitudinally assessed using a multivariable multinomial logistic regression model. RESULTS: At inclusion, 589 patients (52%) had continuous pain, 231 patients (20%) had intermittent pain and 311 patients (28%) had no pain. Patients with continuous pain had more severe pain, used more opioids and neuropathic pain medication, and had a lower quality of life. There were no differences between pain patterns for morphological findings on imaging, disease duration and treatment. During a median follow-up of 47 months, 552 of 905 patients (61%) alternated at least once between pain patterns. All alternations were associated with the Visual Analogue Scale pain intensity score and surgery was only associated with the change from pain to no pain. CONCLUSION: Continuous and intermittent pain patterns in chronic pancreatitis do not seem to be the result of distinctly different pathophysiological entities. The subjectively reported character of pain is not related to imaging findings or disease duration. Pain patterns often change over time and are merely a feature of how severity of pain is experienced.

Colon-specific tablets containing 5-fluorouracil microsponges for colon cancer targeting.

Most anticancer medications undergo major first-pass metabolism in the intestinal wall, the liver, or both. 5-fluorouracil (5-FU) is known to have erratic oral bioavailability due to first-pass metabolism. The present study aimed to develop 5-FU-loaded microsponges (MS) compressed in enteric-coated tablets as a new colon targeting to colorectal cancer. MS was prepared as a controlled release system for 5-FU and characterized for drug encapsulation efficiency, and surface morphology. Further, hydroxypropyl methylcellulose (HPMC) was mixed with pectin and characterized for their flow as a tablet coat enclosing the core tablets of 5-FU-MS. Moreover, in vitro drug release behavior was studied in different pH media, while the X-ray imaging was used to monitor the in vivo movement of prepared tablets containing 5-FU-MS throughout the GI system. The results showed that MS were spherical in shape and have several pores on their surfaces. The encapsulation efficiency was from 71.80 ± 1.62% - 101.3 ± 2.60%, while the particle size was from 53.11 ± 41.03 - 118.12 ± 48.21 nm. The formulated tablets were fulfilling all official and other specifications and exhibited sustained release of 5-FU only inside the colon. The in vivo human volunteer study of X-ray has shown that the tablets ultimately reached the colon without disturbing in the upper GI system. The obtained carrier formulation is considered as a novel system to deliver 5-FU to the colon tumor with 100% targeting without any drug release in the upper GIT or first-pass metabolism.

Evaluation of the implementation of the Back Skills Training (BeST) programme using online training: a cohort implementation study.

OBJECTIVES: 1) Evaluate implementation of the Back Skills Training (BeST) programme, a group cognitive behavioural approach for patients with low back pain (LBP) developed for a clinical trial, into the National Health Service (NHS) in the United Kingdom; 2) Compare patient outcomes with the BeST Trial results. DESIGN: Two stage observational cohort implementation study. PARTICIPANTS: Stage 1: NHS Clinicians enrolled in BeST online training. Stage 2: Patients with LBP attending NHS physiotherapy departments and enrolled in the BeST programme. INTERVENTION: An online training and implementation programme. OUTCOMES: Stage 1: LBP attitudes and beliefs, self-rated competence, intention and actual implementation were collected before, immediately, 4- and 12-months post-training. Stage 2: Patients rated pain, function, recovery and satisfaction before and up to one year after attending the BeST programme. RESULTS: Stage 1: 1324 clinicians (157 NHS Trusts) enrolled in the training; 586 (44%) clinicians (101 NHS Trusts) completed training; 443/586 (76%) clinicians provided post-training data; 253/443 (57%) clinicians intended to implement the programme; 148/381 (39%) clinicians (54 NHS Trusts) provided follow-up data; 49/148 (33.1%) clinicians (27 NHS Trusts) implemented the programme. Attitudes and beliefs shifted towards a biopsychosocial model post-training. Stage 2: 923 patients were enrolled. Patients reported improvements in function (mean change: 1.55; 95%CI: 1.25, 1.86) and pain (-0.84; -1.1, -0.58) at follow-up. The majority rated themselves improved and satisfied with the programme. CONCLUSION: Online training had good reach into NHS Trusts although, not everyone went onto implement the programme. Improvements in function that were consistent with the original trial were demonstrated.

Treatment of newly diagnosed glioblastoma in the elderly: a network meta-analysis.

BACKGROUND: A glioblastoma is a fatal type of brain tumour for which the standard of care is maximum surgical resection followed by chemoradiotherapy, when possible. Age is an important consideration in this disease, as older age is associated with shorter survival and a higher risk of treatment-related toxicity. OBJECTIVES: To determine the most effective and best-tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma. To summarise current evidence for the incremental resource use, utilities, costs and cost-effectiveness associated with these approaches. SEARCH METHODS: We searched electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to 3 April 2019, and the NHS Economic Evaluation Database (EED) up to database closure. We handsearched clinical trial registries and selected neuro-oncology society conference proceedings from the past five years. SELECTION CRITERIA: Randomised trials (RCTs) of treatments for glioblastoma in elderly people. We defined 'elderly' as 70+ years but included studies defining 'elderly' as over 65+ years if so reported. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for study selection and data extraction. Where sufficient data were available, treatment options were compared in a network meta-analysis (NMA) using Stata software (version 15.1). For outcomes with insufficient data for NMA, pairwise meta-analysis were conducted in RevMan. The GRADE approach was used to grade the evidence. MAIN RESULTS: We included 12 RCTs involving approximately 1818 participants. Six were conducted exclusively among elderly people (either defined as 65 years or older or 70 years or older) with newly diagnosed glioblastoma, the other six reported data for an elderly subgroup among a broader age range of participants. Most participants were capable of self-care. Study quality was commonly undermined by lack of outcome assessor blinding and attrition. NMA was only possible for overall survival; other analyses were pair-wise meta-analyses or narrative syntheses. Seven trials contributed to the NMA for overall survival, with interventions including supportive care only (one trial arm); hypofractionated radiotherapy (RT40; four trial arms); standard radiotherapy (RT60; five trial arms); temozolomide (TMZ; three trial arms); chemoradiotherapy (CRT; three trial arms); bevacizumab with chemoradiotherapy (BEV_CRT; one trial arm); and bevacizumab with radiotherapy (BEV_RT). Compared with supportive care only, NMA evidence suggested that all treatments apart from BEV_RT prolonged survival to some extent. Overall survival High-certainty evidence shows that CRT prolongs overall survival (OS) compared with RT40 (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.56 to 0.80) and low-certainty evidence suggests that CRT may prolong overall survival compared with TMZ (TMZ versus CRT: HR 1.42, 95% CI 1.01 to 1.98). Low-certainty evidence also suggests that adding BEV to CRT may make little or no difference (BEV_CRT versus CRT: HR 0.83, 95% CrI 0.48 to 1.44). We could not compare the survival effects of CRT with different radiotherapy fractionation schedules (60 Gy/30 fractions and 40 Gy/15 fractions) due to a lack of data. When treatments were ranked according to their effects on OS, CRT ranked higher than TMZ, RT and supportive care only, with the latter ranked last. BEV plus RT was the only treatment for which there was no clear benefit in OS over supportive care only.   One trial comparing tumour treating fields (TTF) plus adjuvant chemotherapy (TTF_AC) with adjuvant chemotherapy alone could not be included in the NMA as participants were randomised after receiving concomitant chemoradiotherapy, not before. Findings from the trial suggest that the intervention probably improves overall survival in this selected patient population. We were unable to perform NMA for other outcomes due to insufficient data. Pairwise analyses were conducted for the following. Quality of life Moderate-certainty narrative evidence suggests that overall, there may be little difference in QoL between TMZ and RT, except for discomfort from communication deficits, which are probably more common with RT (1 study, 306 participants, P = 0.002). Data on QoL for other comparisons were sparse, partly due to high dropout rates, and the certainty of the evidence tended to be low or very low. Progression-free survival High-certainty evidence shows that CRT increases time to disease progression compared with RT40 (HR 0.50, 95% CI 0.41 to 0.61); moderate-certainty evidence suggests that RT60 probably increases time to disease progression compared with supportive care only (HR 0.28, 95% CI 0.17 to 0.46), and that BEV_RT probably increases time to disease progression compared with RT40 alone (HR 0.46, 95% CI 0.27 to 0.78). Evidence for other treatment comparisons was of low- or very low-certainty. Severe adverse events Moderate-certainty evidence suggests that TMZ probably increases the risk of grade 3+ thromboembolic events compared with RT60 (risk ratio (RR) 2.74, 95% CI 1.26 to 5.94; participants = 373; studies = 1) and also the risk of grade 3+ neutropenia, lymphopenia, and thrombocytopenia. Moderate-certainty evidence also suggests that CRT probably increases the risk of grade 3+ neutropenia, leucopenia and thrombocytopenia compared with hypofractionated RT alone. Adding BEV to CRT probably increases the risk of thromboembolism (RR 16.63, 95% CI 1.00 to 275.42; moderate-certainty evidence). Economic evidence There is a paucity of economic evidence regarding the management of newly diagnosed glioblastoma in the elderly. Only one economic evaluation on two short course radiotherapy regimen (25 Gy versus 40 Gy) was identified and its findings were considered unreliable. AUTHORS' CONCLUSIONS: For elderly people with glioblastoma who are self-caring, evidence suggests that CRT prolongs survival compared with RT and may prolong overall survival compared with TMZ alone. For those undergoing RT or TMZ therapy, there is probably little difference in QoL overall. Systemic anti-cancer treatments TMZ and BEV carry a higher risk of severe haematological and thromboembolic events and CRT is probably associated with a higher risk of these events. Current evidence provides little justification for using BEV in elderly patients outside a clinical trial setting. Whilst the novel TTF device appears promising, evidence on QoL and tolerability is needed in an elderly population. QoL and economic assessments of CRT versus TMZ and RT are needed. More high-quality economic evaluations are needed, in which a broader scope of costs (both direct and indirect) and outcomes should be included.

Natural Course and Treatment of Pancreatic Exocrine Insufficiency in a Nationwide Cohort of Chronic Pancreatitis.

OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is a common complication of chronic pancreatitis. However, little is known about the natural course of PEI and the effect of pancreatic enzyme replacement therapy on symptoms. The aim of this study was to evaluate the natural course and treatment of PEI in a nationwide cohort of patients with chronic pancreatitis. METHODS: Patients with chronic pancreatitis were selected from the multicenter Dutch Chronic Pancreatitis Registry. Patients were classified in 3 groups: definite PEI, potential PEI, and no PEI. Definite PEI and no PEI were compared regarding the course of disease, symptoms, treatment, and quality of life. RESULTS: Nine hundred eighty-seven patients were included from 29 centers, of which 304 patients (31%) had definite PEI; 451 (46%), potentially PEI; and 232 (24%), no PEI. Patients with definite PEI had significantly more malabsorption symptoms, a lower body mass index, and aberrant defecation. Lowered quality of life was not independently associated with PEI. Of the PEI patients using pancreatic enzyme replacement therapy, 47% still reported steatorrhea. CONCLUSIONS: Pancreatic exocrine insufficiency is associated with malabsorption symptoms and a lower body mass index. Some form of pancreatic enzyme replacement therapy is reasonably effective in alleviating malabsorption symptoms, but improvement of treatment is needed.

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial.

Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function. Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes. Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018. Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed. Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality. Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach. Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings. Trial Registration: ISRCTN Identifier: ISRCTN45877994.

Multidimensional Test Assembly Using Mixed-Integer Linear Programming: An Application of Kullback-Leibler Information.

Many educational testing programs require different test forms with minimal or no item overlap. At the same time, the test forms should be parallel in terms of their statistical and content-related properties. A well-established method to assemble parallel test forms is to apply combinatorial optimization using mixed-integer linear programming (MILP). Using this approach, in the unidimensional case, Fisher information (FI) is commonly used as the statistical target to obtain parallelism. In the multidimensional case, however, FI is a multidimensional matrix, which complicates its use as a statistical target. Previous research addressing this problem focused on item selection criteria for multidimensional computerized adaptive testing (MCAT). Yet these selection criteria are not directly transferable to the assembly of linear parallel test forms. To bridge this gap the authors derive different statistical targets, based on either FI or the Kullback-Leibler (KL) divergence, that can be applied in MILP models to assemble multidimensional parallel test forms. Using simulated item pools and an item pool based on empirical items, the proposed statistical targets are compared and evaluated. Promising results with respect to the KL-based statistical targets are presented and discussed.

Optimizing Patient Selection for Laparoscopic and Open Colorectal Cancer Resections: A National Surgical Quality Improvement Program-Matched Analysis.

The aim of this study was to identify patients undergoing colorectal cancer (CRC) resection who might benefit specifically from either an open or laparoscopic approach. From the NSQIP database (2012-2013), patients who underwent laparoscopic colectomy (LC) or open colectomy (OC) for CRC were identified. The two groups were matched and compared in terms of any, medical, and surgical complications. A wide range of patient characteristics were collected and analyzed. Interaction analysis was performed in a multivariable regression model to identify risk factors that may make LC or OC more beneficial in certain subgroups of patients. Overall, OC (n = 6593) was associated with a significantly higher risk of any [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.87-2.20], surgical (OR 1.98, 95% CI 1.82-2.16), and medical (OR 1.71, 95% CI 1.51-1.94) complications than LC (n = 6593). No subgroup of patients benefited from an open approach. Patients with obesity (BMI > 30) (P = 0.03) and older age (>65 years) (P = 0.01) benefited more than average from a laparoscopic approach. For obese patients, LC was associated with less overall complications (OC vs LC: OR 1.92 obese vs 1.21 nonobese patients). For elderly patients, LC was more preferable regarding the risk of medical complications (OC vs LC OR of 1.91 vs 1.34 for younger patients). No subgroup of CRC patients benefited specifically more from an open colorectal resection. This supports that the laparoscopic technique should be performed whenever feasible. For the obese and elderly patients, the benefits of the laparoscopic approach were more pronounced.

Web-based rehabilitation interventions for people with rheumatoid arthritis: A systematic review.

BACKGROUND: Rehabilitation approaches for people with rheumatoid arthritis include joint protection, exercises and self-management strategies. Health interventions delivered via the web have the potential to improve access to health services overcoming time constraints, physical limitations, and socioeconomic and geographic barriers. The objective of this review is to determine the effects of web-based rehabilitation interventions in adults with rheumatoid arthritis. METHODS: Randomised controlled trials that compared web-based rehabilitation interventions with usual care, waiting list, no treatment or another web-based intervention in adults with rheumatoid arthritis were included. The outcomes were pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge, physical activity and adverse effects. Methodological quality was assessed using the Cochrane Risk of Bias tool and quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Six source documents from four trials ( n = 567) focusing on self-management, health information or physical activity were identified. The effects of web-based rehabilitation interventions on pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge and physical activity are uncertain because of the very low quality of evidence mostly from small single trials. Adverse effects were not reported. CONCLUSION: Large, well-designed trials are needed to evaluate the clinical and cost-effectiveness of web-based rehabilitation interventions in rheumatoid arthritis.

Impact of characteristics of organ failure and infected necrosis on mortality in necrotising pancreatitis.

OBJECTIVE: In patients with pancreatitis, early persisting organ failure is believed to be the most important cause of mortality. This study investigates the relation between the timing (onset and duration) of organ failure and mortality and its association with infected pancreatic necrosis in patients with necrotising pancreatitis. DESIGN: We performed a post hoc analysis of a prospective database of 639 patients with necrotising pancreatitis from 21 hospitals. We evaluated the onset, duration and type of organ failure (ie, respiratory, cardiovascular and renal failure) and its association with mortality and infected pancreatic necrosis. RESULTS: In total, 240 of 639 (38%) patients with necrotising pancreatitis developed organ failure. Persistent organ failure (ie, any type or combination) started in the first week in 51% of patients with 42% mortality, in 13% during the second week with 46% mortality and in 36% after the second week with 29% mortality. Mortality in patients with persistent multiple organ failure lasting <1 week, 1-2 weeks, 2-3 weeks or longer than 3 weeks was 43%, 38%, 46% and 52%, respectively (p=0.68). Mortality was higher in patients with organ failure alone than in patients with organ failure and infected pancreatic necrosis (44% vs 29%, p=0.04). However, when excluding patients with very early mortality (within 10 days of admission), patients with organ failure with or without infected pancreatic necrosis had similar mortality rates (28% vs 34%, p=0.33). CONCLUSION: In patients with necrotising pancreatitis, early persistent organ failure is not associated with increased mortality when compared with persistent organ failure which develops further on during the disease course. Furthermore, no association was found between the duration of organ failure and mortality.

Sample size calculations are poorly conducted and reported in many randomized trials of hip and knee osteoarthritis: results of a systematic review.

OBJECTIVES: To review the methodology and reporting of sample size calculations in a contemporary sample of trials in osteoarthritis. STUDY DESIGN AND SETTING: Randomized trials in hip and/or knee osteoarthritis published in 2016 were identified by searching MEDLINE, Cochrane library, CINAHL, EMBASE, PsycINFO, PEDro, and AMED until March 31, 2017. Data were extracted on study characteristics, methods used to calculate the sample size, and the reporting and justification of components used in the sample size calculation. We attempted to replicate the sample size calculation using the reported information. RESULTS: This review included 116 trials. Seventy-eight (67%, n = 78/116) reported a power calculation. Less than a quarter reported all core components of the sample size calculation (21%, n = 16/78). The sample size calculation was only reproducible in 53% of the trials that reported a power calculation (n = 41/78). The replicated calculation produced a sample size over 10% larger than the reported value in 12% of trials (n = 9/78). Insufficient information was reported to allow the sample size calculation to be replicated in a quarter of trials (27%, n = 21/78). CONCLUSION: Sample size calculations in trials of hip and knee osteoarthritis are not adequately reported, and the calculation frequently cannot be reproduced.

Sample size of surgical randomized controlled trials: a lack of improvement over time.

BACKGROUND: Interpretation of randomized controlled trials (RCTs) without a significant difference regarding the primary outcome (negative RCTs) is frequently challenging, due to concerns about sample size and thus sufficient statistical power. We aimed to assess the adequacy of sample size and corresponding power of surgical RCTs. METHODS: We previously identified all surgical RCTs available in PubMed in two distinct years a decade apart (1999 and 2009). For all "negative" trials, we estimated whether the sample size of the trial was appropriate to detect a difference in the primary outcome measure. The main outcome measure was a sufficient sample size to detect large, medium, and small treatment effects. We also performed a post hoc power analysis based on the actual observed effect difference. RESULTS: A total of 228 negative RCTs (74 in 1999 and 121 in 2009) were included. The median sample size was 76 (± 222) and 80 (± 163) in 1999 and 2009, respectively. Sample size calculation was increasingly reported from 40% in 1999 to 54% in 2009 (P = 0.02). The proportion of studies adequately powered to detect large (57% versus 68%), medium (26% versus 25%), or small (8% versus 7%) differences did not differ significantly between 1999 and 2009, respectively. To reach sufficient power, the required increases in sample size were 130%, 240%, and 1032% for large, medium, and small differences, respectively. Reporting a sample size calculation was the only independent predictor for adequate power. CONCLUSIONS: Despite slight improvement in the reporting of a sample size calculation, about a third of surgical trials remains underpowered to demonstrate differences that are likely to be clinically significant. Increased attention of researchers, medical ethical boards, and journal editors is required to reduce potentially wasted resources on underpowered trials.

A Generalized Speed-Accuracy Response Model for Dichotomous Items.

We propose a generalization of the speed-accuracy response model (SARM) introduced by Maris and van der Maas (Psychometrika 77:615-633, 2012). In these models, the scores that result from a scoring rule that incorporates both the speed and accuracy of item responses are modeled. Our generalization is similar to that of the one-parameter logistic (or Rasch) model to the two-parameter logistic (or Birnbaum) model in item response theory. An expectation-maximization (EM) algorithm for estimating model parameters and standard errors was developed. Furthermore, methods to assess model fit are provided in the form of generalized residuals for item score functions and saddlepoint approximations to the density of the sum score. The presented methods were evaluated in a small simulation study, the results of which indicated good parameter recovery and reasonable type I error rates for the residuals. Finally, the methods were applied to two real data sets. It was found that the two-parameter SARM showed improved fit compared to the one-parameter SARM in both data sets.