One leg testing in hip and knee osteoarthritis: A comparison with a two-leg oriented functional outcome measure and self-reported functional measures.

OBJECTIVE: To compare the responsiveness of two unilateral lower-limb performance-based tests, the one-leg rise test and the maximal step-up test, with the bilateral 30-second chair-stand test and the self-reported measure of physical function (HOOS/KOOS). Specific aims were to evaluate responsiveness, floor/ceiling effect and association between the instruments. METHOD: Data was included from 111 participants, mean age 61.3 years (8.3), with clinically verified hip or knee osteoarthritis, who reported less than 150 minutes/week of moderate or vigorous intensity physical activity. Responsiveness, how well the instruments captured improvements, was measured as Cohen's standardised mean difference for effect size, and was assessed from baseline to 12 months following a physical activity intervention. Other assessments were floor and ceiling effects, and correlations between tests. RESULTS: The maximal step-up test had an effect size of 0.57 (95% CI 0.37, 0.77), the 30-second chair-stand 0.48 (95% CI 0.29, 0.68) and the one-leg rise test 0.12 (95% CI 0.60, 0.31). The one-leg rise test had a floor effect as 72% of the participants scored zero at baseline and 63% at 12 months. The correlation between performance-based tests and questionnaires was considered to be minor (r = 0.188 to 0.226) (p = 0.018 to 0.048). CONCLUSION: The unilateral maximal step-up test seems more responsive to change in physical function compared to the bilateral 30-second chair-stand test, although the tests did not differ statistically in effect size. The maximal step-up test provides specific information about each leg for the individual and allows for comparison between the legs.

Step-up approach for the treatment of infected necrotising pancreatitis: real life data from a single-centre experience with long-term follow-up.

BACKGROUND: About 20% of patients with acute pancreatitis develop a necrotising form with a worse prognosis due to frequent appearance of organ failure(s) and/or infection of necrosis. Aims of the present study was to evaluate the "step up" approach treatment of infected necrosis in terms of: feasibility, success in resolving infection, morbidity of procedures, risk factors associated with death and long-term sequels. METHODS: In this observational retrospective monocentric study in the real life, necrotizing acute pancreatitis at the stage of infected walled-off necrosis were treated as follow: first step with drainage (radiologic and/or endoscopic-ultrasound-guided with lumen apposing metal stent); in case of failure, minimally invasive necrosectomy sessions(s) by endoscopy through the stent and/or via retroperitoneal surgery (step 2); If necessary open surgery as a third step. Efficacy was assessed upon to a composite clinical-biological criterion: resolution of organ failure(s), decrease of at least two of clinico-biological criteria among fever, CRP serum level, and leucocytes count). RESULTS: Forty-one consecutive patients were treated. The step-up strategy: (i) was feasible in 100% of cases; (ii) allowed the infection to be resolved in 33 patients (80.5%); (iii) Morbidity was mild and rapidly resolutive; (iv) the mortality rate at 6 months was of 19.5% (significant factors: SIRS and one or more organ failure(s) at admission, fungal infection, size of the largest collection ≥ 16 cm). During the follow-up (median 72 months): 27% of patients developed an exocrine pancreatic insufficiency, 45% developed or worsened a previous diabetes, 24% had pancreatic fistula and one parietal hernia. CONCLUSIONS: Beside a very good feasibility, the step-up approach for treatment of infected necrotizing pancreatitis in the real life displays a clinico-biological efficacy in 80% of cases with acceptable morbidity, mortality and long-term sequels regarding the severity of the disease.

Medial-pivot total knee arthroplasty enhances tibiofemoral axial rotation stability in weight-bearing mid-range flexion compared to posterior-stabilised system.

PURPOSE: Total knee arthroplasty (TKA) stands as a primary intervention for severe knee ailments, yet concerns remain regarding postoperative patient satisfaction and flexion instability. This study aims to evaluate the in-vivo kinematics of medial-pivot (MP) and posterior-stabilised (PS) designs during step-up activity, in comparison to the kinematics of the nonoperated contralateral knee. METHODS: Sixteen patients with PS-TKA and 14 with MP-TKA were retrospectively examined. Clinical outcomes were assessed using patient-completed questionnaires. Motion during step-up was captured using a dual fluoroscopic system. Statistical analysis was applied to evaluate the in-vivo tibiofemoral six-degree-of-freedom kinematics and articular contact positions between the two groups. RESULTS: Despite being older, patients in the MP group reported higher postoperative subjective scores for weight-bearing functional activities. The axial rotation centres of MP-TKA located on the medial tibial plateau exhibited less variance compared to PS-TKA and contralateral knees. Compared to the contralateral knee (contralateral to medial-pivot [C-MP] or contralateral to posterior-stabilised [C-PS]), the MP group exhibited limited range of motion in terms of anteroposterior translation (MP: 3.6 ± 1.3 mm vs. C-MP: 7.4 ± 2.5 mm, p < 0.01) and axial rotation (MP: 6.6 ± 1.9° vs. C-MP: 10.3 ± 4.9°, p = 0.02), as well as in the PS group for anteroposterior translation (PS: 3.9 ± 1.7 mm vs. C-PS: 7.2 ± 3.7 mm, p < 0.01). CONCLUSION: The MP group with better postoperative ratings demonstrated a more stable MP axial rotation pattern during step-up activity compared to the PS group, underscoring the pivotal role of prosthetic design in optimising postoperative rehabilitation and functional recovery. LEVEL OF EVIDENCE: Level III.

Endoscopic Ultrasound-Guided Drainage of Pancreatic Fluid Collections: Not All Queries Are Already Solved.

Pancreatic fluid collections (PFCs) are well-known complications of acute pancreatitis. The overinfection of these collections leads to a worsening of the prognosis with an increase in the morbidity and mortality rate. The primary strategy for managing infected pancreatic necrosis (IPN) or symptomatic PFCs is a minimally invasive step-up approach, with endosonography-guided (EUS-guided) transmural drainage and debridement as the preferred and less invasive method. Different stents are available to drain PFCs: self-expandable metal stents (SEMSs), double pigtail stents (DPPSs), or lumen-apposing metal stents (LAMSs). In particular, LAMSs are useful when direct endoscopic necrosectomy is needed, as they allow easy access to the necrotic cavity; however, the rate of adverse events is not negligible, and to date, the superiority over DPPSs is still debated. Moreover, the timing for necrosectomy, the drainage technique, and the concurrent medical management are still debated. In this review, we focus attention on indications, timing, techniques, complications, and particularly on aspects that remain under debate concerning the EUS-guided drainage of PFCs.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.

Computed tomography imaging-based predictors of the need for a step-up approach after initial endoscopic ultrasound-guided transmural drainage for pancreatic fluid collections.

BACKGROUND: A step-up approach is recommended as a new treatment algorithm for pancreatic fluid collections (PFCs). However, determining which patients with PFCs require a step-up approach after endoscopic ultrasound-guided transmural drainage (EUS-TD) is unclear. If the need for a step-up approach could be predicted, it could be performed early for relevant patients. We aimed to identify PFC-related predictive factors for a step-up approach after EUS-TD. METHODS: This retrospective cohort study included consecutive patients who had undergone EUS-TD for PFCs from January 2008 to May 2020. Multivariable logistic regression analyses were performed to investigate PFC factors related to requiring a step-up approach. A step-up approach was performed for patients who did not respond clinically to EUS-TD. RESULTS: We enrolled 81 patients, of whom 25 (30.9%) required a step-up approach. In multivariate logistic regression analysis, the pre-EUS-TD number of PFC-occupied regions ≥ 3 (multivariate odds ratio [OR] 16.2, 95% confidence interval [CI] 2.68-97.6, P = 0.002), the post-EUS-TD PFC-remaining percentage ≥ 35% (multivariate OR 19.9, 95% CI 2.91-136.1, P = 0.002), and a positive sponge sign, which is a distinctive computed tomography finding in the early stage after EUS-TD (multivariate OR 6.26, 95% CI 1.33-29.3, P = 0.020), were independent predictive factors associated with requiring a step-up approach for PFCs. CONCLUSION: Pre-EUS-TD PFC-occupied regions, post-EUS-TD PFC-remaining percentage, and a positive sponge sign were predictors of the need for a step-up approach. Patients with PFC with these findings should be offered a step-up approach whereas conservative treatment is recommended for patients without these findings. CLINICAL REGISTRATION NUMBER: UMIN 000030898.

Multiple test procedures of disease prevalence based on stratified partially validated series in the presence of a gold standard.

This paper discusses the problem of disease prevalence in clinical studies, focusing on multiple comparisons based on stratified partially validated series in the presence of a gold standard. Five test statistics, including two Wald-type test statistics, the inverse hyperbolic tangent transformation test statistic, likelihood ratio test statistic, and score test statistic, are proposed to conduct multiple comparisons. To control the overall type I error rate, several adjustment procedures are developed, namely the Bonferroni, Single-step adjusted MaxT, Single-step adjusted MinP, Holm's Step-down, and Hochberg's step-up procedures, based on these test statistics. The performance of the proposed methods is evaluated through simulation studies in terms of the empirical type I error rate and empirical power. Simulation results show that the Single-step adjusted MaxT procedure and Single-step adjusted MinP procedure generally outperform the other three procedures, and these two test procedures based on all test statistics have satisfactory performance. Notably, the Single-step adjusted MinP procedure tends to exhibit higher empirical power than the Single-step adjusted MaxT procedure. Furthermore, the Step-down and Step-up procedures show greater power compared to the Bonferroni method. The study also observes that as the validated ratio increases, the empirical type I errors of all test procedures approach the nominal level while maintaining higher power. Two real examples are presented to illustrate the proposed methods.

Clinical Outcomes of the Endoscopic Step-Up Approach with or without Radiology-Guided Percutaneous Drainage for Symptomatic Walled-Off Pancreatic Necrosis.

Background and objectives: Symptomatic walled-off pancreatic necrosis is a serious local complication of acute necrotising pancreatitis. The endoscopic step-up approach is the standard treatment for symptomatic walled-off pancreatic necrosis; however, adjunctive radiologic percutaneous drainage for this condition is controversial. This study compared the clinical and radiologic resolution of walled-off pancreatic necrosis achieved with the endoscopic step-up approach with or without radiology-guided percutaneous drainage. Material and Methods: This retrospective, single-centre cohort study enrolled patients with symptomatic walled-off pancreatic necrosis who underwent endoscopic transmural drainage (ETD) followed by directed endoscopic necrosectomy (DEN) with or without radiology-guided drainage. A total of 34 patients (endoscopic approach, n = 22; combined modality approach, n = 12) underwent the endoscopic step-up approach (ETD followed by DEN). Baseline characteristics, clinical success, and resolution of necrosis were compared between groups. Results: All patients achieved symptom resolution from walled-off pancreatic necrosis. The mean patient age was 58.4 years, and 21 (61.8%) were men. Following treatment with the endoscopic approach and combined modality approach, clinical success was achieved in 90.9% of patients within 11.5 days, and 66.7% of patients within 16.5 days, respectively. Both length of hospital stay (55 days vs. 71 days; p = 0.071) and time to complete radiologic resolution were shorter (93 days vs. 124 days; p = 0.23) in the endoscopic approach group. Conclusion: Both the endoscopic step-up approach and the CMD approach resulted in a favourably high clinical resolution rates in patients with symptomatic WON. However, clinical success rates seemed to be higher, and the length of hospital stay tended to be shorter in the endoscopic approach than in the CMD approach, as well as the significantly shorter necrosectomy time in each procedure was observed. Of note, these findings might be from some inherited differences in baseline characteristics of the patients between the two groups, and a randomized controlled trial with a larger sample size to verify these results is warranted.

Position of surgical treatment in step-up management of severe acute pancreatitis.

INTRODUCTION: The incidence of acute pancreatitis has been increasing over the past twenty years and there is still no causal treatment available. Although cases of severe acute pancreatitis account for only about a fifth of all cases of acute pancreatitis, high morbidity and lethality call for an optimization and unification of treatment procedures. METHODS: We operated on 27 patients suffering from severe acute pancreatitis in the past five years. We compared selected parameters such as gender, age, body mass index, aetiology, presence of type 2 diabetes, BISAP score, previous minimally invasive treatment and presence of the intraabdominal compartment syndrome. RESULTS: The average age of men and women was similar in our group. Most patients were overweight or obese. Alcoholic aetiology was more common in men while biliary aetiology prevailed in women. The mortality rate was 26% in our group. The intra-abdominal compartment syndrome followed by emergency decompression surgery was present in one fourth of the patients. A minimally invasive approach was used in approximately in one half of the patients, and surgical treatment was used only in cases where the minimally invasive approach failed. CONCLUSION: After each surgical revision, clinical deterioration of the patient´s condition occurs during the first two to three days in response to operative stress. Therefore, the current trend in the treatment of acute pancreatitis is to proceed as conservatively as possible, or using the minimally invasive approach, and surgical treatment should be reserved only for conditions that cannot be managed otherwise. If surgical treatment is used, it is advisable to perform cholecystectomy, whatever the aetiology of the pancreatitis.

Severe Pancreatitis Multidisciplinary Working Group: Exploratory Analysis to Optimize Care and Cost.

INTRODUCTION: The minimally invasive step-up approach to pancreatitis improves outcomes. Multidisciplinary working groups may best facilitate this approach. However, support for these working groups requires funding. We hypothesize that patients requiring surgical debridement generate sufficient revenue to sustain these working groups. Furthermore, patients selected for surgical debridement by the working group will have a higher rate of percutaneous and endoscopic intervention in adherence to the step-up approach. METHODS: We conducted an observational cohort study of all patients with severe acute and/or necrotizing pancreatitis whose care was overseen by our multidisciplinary working group (October 2015 through January 2019). Patient demographics, hospital treatments, and outcomes data were compared between those who underwent surgical debridement and those who did not. Hospital billing data were also collected from those who are undergoing surgical debridement and compared to institutional benchmarks for financial sustainability. RESULTS: A total of 108 patients received care overseen by the working group, 10 of which progressed to surgical debridement. The mean contribution margin percentages for each patient in the surgical debridement group were higher than the threshold value for financial sustainability, 39% (60.34% ± 16.66%; P = 0.004). Patients in the surgical debridement group were more likely to undergo intervention by interventional radiologist (odds ratio, 1.58; P = 0.005). The mortality was higher in the nonsurgical debridement group (odds ratio, 15; P = 0.008). CONCLUSIONS: Our multidisciplinary working group delivered step-up care to patients with pancreatitis. Patients requiring surgical debridement generated a significantly positive contribution margin that could be used to help support the costs associated with providing multidisciplinary care.

Improved Quasi-Z-Source High Step-Up DC-DC Converter Based on Voltage-Doubler Topology.

The step-up DC-DC converter is widely used for applications such as IoT sensor nodes, energy harvesting, and photovoltaic (PV) systems. In this article, a new topological quasi-Z-source (QZ) high step-up DC-DC converter for the PV system is proposed. The topology of this converter is based on the voltage-doubler circuits. Compared with a conventional quasi-Z-source DC-DC converter, the proposed converter features low voltage ripple at the output, the use of a common ground switch, and low stress on circuit components. The new topology, named a low-side-drive quasi-Z-source boost converter (LQZC), consists of a flying capacitor (CF), the QZ network, two diodes, and a N-channel MOS switch. A 60 W laboratory prototype DC-DC converter achieved 94.9% power efficiency.

American Gastroenterological Association Clinical Practice Update: Management of Pancreatic Necrosis.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert recommendations regarding the clinical care of patients with pancreatic necrosis and to offer concise best practice advice for the optimal management of patients with this highly morbid condition. METHODS: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This review is framed around the 15 best practice advice points agreed upon by the authors, which reflect landmark and recent published articles in this field. This expert review also reflects the experiences of the authors, who are advanced endoscopists or hepatopancreatobiliary surgeons with extensive experience in managing and teaching others to care for patients with pancreatic necrosis. BEST PRACTICE ADVICE 1: Pancreatic necrosis is associated with substantial morbidity and mortality and optimal management requires a multidisciplinary approach, including gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition. In situations where clinical expertise may be limited, consideration should be given to transferring patients with significant pancreatic necrosis to an appropriate tertiary-care center. BEST PRACTICE ADVICE 2: Antimicrobial therapy is best indicated for culture-proven infection in pancreatic necrosis or when infection is strongly suspected (ie, gas in the collection, bacteremia, sepsis, or clinical deterioration). Routine use of prophylactic antibiotics to prevent infection of sterile necrosis is not recommended. BEST PRACTICE ADVICE 3: When infected necrosis is suspected, broad-spectrum intravenous antibiotics with ability to penetrate pancreatic necrosis should be favored (eg, carbapenems, quinolones, and metronidazole). Routine use of antifungal agents is not recommended. Computed tomography-guided fine-needle aspiration for Gram stain and cultures is unnecessary in the majority of cases. BEST PRACTICE ADVICE 4: In patients with pancreatic necrosis, enteral feeding should be initiated early to decrease the risk of infected necrosis. A trial of oral nutrition is recommended immediately in patients in whom there is absence of nausea and vomiting and no signs of severe ileus or gastrointestinal luminal obstruction. When oral nutrition is not feasible, enteral nutrition by either nasogastric/duodenal or nasojejunal tube should be initiated as soon as possible. Total parenteral nutrition should be considered only in cases where oral or enteral feeds are not feasible or tolerated. BEST PRACTICE ADVICE 5: Drainage and/or debridement of pancreatic necrosis is indicated in patients with infected necrosis. Drainage and/or debridement may be required in patients with sterile pancreatic necrosis and persistent unwellness marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications, including gastrointestinal luminal obstruction; biliary obstruction; recurrent acute pancreatitis; fistulas; or persistent systemic inflammatory response syndrome. BEST PRACTICE ADVICE 6: Pancreatic debridement should be avoided in the early, acute period (first 2 weeks), as it has been associated with increased morbidity and mortality. Debridement should be optimally delayed for 4 weeks and performed earlier only when there is an organized collection and a strong indication. BEST PRACTICE ADVICE 7: Percutaneous drainage and transmural endoscopic drainage are both appropriate first-line, nonsurgical approaches in managing patients with walled-off pancreatic necrosis (WON). Endoscopic therapy through transmural drainage of WON may be preferred, as it avoids the risk of forming a pancreatocutaneous fistula. BEST PRACTICE ADVICE 8: Percutaneous drainage of pancreatic necrosis should be considered in patients with infected or symptomatic necrotic collections in the early, acute period (<2 weeks), and in those with WON who are too ill to undergo endoscopic or surgical intervention. Percutaneous drainage should be strongly considered as an adjunct to endoscopic drainage for WON with deep extension into the paracolic gutters and pelvis or for salvage therapy after endoscopic or surgical debridement with residual necrosis burden. BEST PRACTICE ADVICE 9: Self-expanding metal stents in the form of lumen-apposing metal stents appear to be superior to plastic stents for endoscopic transmural drainage of necrosis. BEST PRACTICE ADVICE 10: The use of direct endoscopic necrosectomy should be reserved for those patients with limited necrosis who do not adequately respond to endoscopic transmural drainage using large-bore, self-expanding metal stents/lumen-apposing metal stents alone or plastic stents combined with irrigation. Direct endoscopic necrosectomy is a therapeutic option in patients with large amounts of infected necrosis, but should be performed at referral centers with the necessary endoscopic expertise and interventional radiology and surgical backup. BEST PRACTICE ADVICE 11: Minimally invasive operative approaches to the debridement of acute necrotizing pancreatitis are preferred to open surgical necrosectomy when possible, given lower morbidity. BEST PRACTICE ADVICE 12: Multiple minimally invasive surgical techniques are feasible and effective, including videoscopic-assisted retroperitoneal debridement, laparoscopic transgastric debridement, and open transgastric debridement. Selection of approach is best determined by pattern of disease, physiology of the patient, experience and expertise of the multidisciplinary team, and available resources. BEST PRACTICE ADVICE 13: Open operative debridement maintains a role in the modern management of acute necrotizing pancreatitis in cases not amenable to less invasive endoscopic and/or surgical procedures. BEST PRACTICE ADVICE 14: For patients with disconnected left pancreatic remnant after acute necrotizing mid-body necrosis, definitive surgical management with distal pancreatectomy should be undertaken in patients with reasonable operative candidacy. Insufficient evidence exists to support the management of the disconnected left pancreatic remnant with long-term transenteric endoscopic stenting. BEST PRACTICE ADVICE 15: A step-up approach consisting of percutaneous drainage or endoscopic transmural drainage using either plastic stents and irrigation or self-expanding metal stents/lumen-apposing metal stents alone, followed by direct endoscopic necrosectomy, and then surgical debridement is reasonable, although approaches may vary based on the available clinical expertise.

Comparison of inflammatory bowel disease relapse after top-down or step-up therapy: a population-based cohort study.

PURPOSE: The therapeutic effect of top-down therapy for inflammatory bowel disease (IBD) has not been fully evaluated in real-world clinical settings. We compared the effectiveness of top-down and step-up therapies for IBD. METHODS: We retrospectively evaluated patients who were admitted with IBD (Crohn's disease [CD] or ulcerative colitis [UC]) between 2012 and 2019 using the nationwide Japan Diagnosis Procedure Combination database. Patients who received immunomodulators or biologic agents at the start of observation were assigned to the top-down group and those who did not were enrolled in the step-up group. Relapse was the primary outcome, a composite outcome defined as surgery, new steroid or immunomodulator use, hospitalization, a new biologic agent, or switching biologic agents. RESULTS: We analyzed 6715 patients (CD, N = 3643; UC, N = 3072). Relapse occurred in 1982 CD cases (54.4%). The cumulative CD relapse incidence was 32.9% at 1 year and 61.3% at 5 years in the top-down group and 30.7% at 1 year and 58.6% at 5 years in the step-up group. Relapse occurred in 2032 UC cases (47.8%). The cumulative relapse incidence was 33.5% at 1 year and 50.0% at 5 years in the top-down group and 35.2% at 1 year and 51.6% at 5 years in the step-up group. No clinical factors associated with relapse were identified in patients with CD or UC. CONCLUSION: Compared with step-up therapy, top-down therapy was not associated with a decreased relapse risk in a real-world population of patients with CD or UC.

Predictive analytics for step-up therapy: Supervised or semi-supervised learning?

BACKGROUND: Step-up therapy is a patient management approach that aims to balance the efficacy, costs and risks posed by different lines of medications. While the initiation of first line medications is a straightforward decision, stepping-up a patient to the next treatment line is often more challenging and difficult to predict. By identifying patients who are likely to move to the next line of therapy, prediction models could be used to help healthcare organizations with resource planning and chronic disease management. OBJECTIVE: To compared supervised learning versus semi-supervised learning to predict which rheumatoid arthritis patients will move from the first line of therapy (i.e., conventional synthetic disease-modifying antirheumatic drugs) to the next line of therapy (i.e., disease-modifying antirheumatic drugs or targeted synthetic disease-modifying antirheumatic drugs) within one year. MATERIALS AND METHODS: Five groups of features were extracted from an administrative claims database: demographics, medications, diagnoses, provider characteristics, and procedures. Then, a variety of supervised and semi-supervised learning methods were implemented to identify the most optimal method of each approach and assess the contribution of each feature group. Finally, error analysis was conducted to understand the behavior of misclassified patients. RESULTS: XGBoost yielded the highest F-measure (42%) among the supervised approaches and one-class support vector machine achieved the highest F-measure (65%) among the semi-supervised approaches. The semi-supervised approach had significantly higher F-measure (65% vs. 42%; p < 0.01), precision (51% vs. 33%; p < 0.01), and recall (89% vs. 59%; p < 0.01) than the supervised approach. Excluding demographic, drug, diagnosis, provider, and procedure features reduced theF-measure from 65% to 61%, 57%, 54%, 51% and 49% respectively (p < 0.01). The error analysis showed that a substantial portion of false positive patients will change their line of therapy shortly after the prediction period. CONCLUSION: This study showed that supervised learning approaches are not an optimal option for a difficult clinical decision regarding step-up therapy. More specifically, negative class labels in step-up therapy data are not a robust ground truth, because the costs and risks associated with higher line of therapy impact objective decision making of patients and providers. The proposed semi-supervised learning approach can be applied to other step-up therapy applications.

Identification of novel step-up regimen of intralesional triamcinolone acetonide in scalp alopecia areata based on a double-blind randomized controlled trial.

Although intralesional triamcinolone acetonide (TA) is the most commonly prescribed treatment for localized alopecia areata (AA), the literature regarding the optimal concentration for attaining better efficacy with the most acceptable side effects is scarce. To compare hair regrowth and local side effects of various concentrations of intralesional TA in scalp AA using clinical and dermoscopic parameters. A double-blind randomized control trial with four treatment groups (10, 5, 2.5 mg/ml TA and normal saline [NS]) was conducted between March 2018 and August 2019. After recruitment, each AA patch was divided into quadrants and randomized before first injection. Injections were given and outcome parameters were analyzed every 4-weekly till 12-weeks. Statistical analysis was done by the R software employing generalized estimation equation. P-value <.05 was considered significant. Out of 105-patients (168-AA patches), 75-patients (121-patches) completed the study. Hair regrowth scale of all TA concentrations was better than NS group (P < .001). Other parameters such as quadrants with poor clinical response and dermoscopic disease activity signs were also favorable in TA groups in comparison to NS. However the evidence of atrophy and telangiectasia was maximum in 10 mg/mL group. 10 mg/mL TA showed a comparatively better response at the cost of increased adverse effects. Based on the clinical benefit and adverse risk assessment from our study, it may be better to start with 2.5 mg/mL intralesional TA in limited scalp AA patients. It can be implied that the concentration of TA can be increased as a step-up regimen based on the serial clinical and dermoscopic response.

Acute recurrent and chronic pancreatitis in children.

Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step-up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non-opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner.

Novel techniques for management of portal system hemorrhage in acute pancreatitis.

Current management of infected pancreatic necrosis is focused on a minimally invasive step-up approach. The step-up approach consists of initial percutaneous or endoscopic drainage of infected pancreatic necrosis, followed, if necessary, by minimally invasive surgical or endoscopic debridement. While there is reduced morbidity and mortality, vascular complications can be life-threatening. Reported vascular complications have been limited to arterial bleeding. Venous bleeding has not been previously reported. We present two cases of portal venous bleeding in patients who underwent treatment for infected pancreatic necrosis with a step-up approach. We discuss the clinical presentation, diagnosis, and initial management. Moreover, we present two different techniques that can be used to successfully manage venous bleeding in patients who have percutaneous drains in place as part of a step-up approach. These techniques involve tamponading the cavity or drain tract with topical hemostatics and direct embolization of the bleeding vein. These experiences can serve as a guide for managing portal venous bleeding in patients with infected pancreatic necrosis.

Treating male partners of women with bacterial vaginosis (StepUp): a protocol for a randomised controlled trial to assess the clinical effectiveness of male partner treatment for reducing the risk of BV recurrence.

BACKGROUND: Bacterial vaginosis (BV) is estimated to affect 1 in 3 women globally and is associated with obstetric and gynaecological sequelae. Current recommended therapies have good short-term efficacy but 1 in 2 women experience BV recurrence within 6 months of treatment. Evidence of male carriage of BV-organisms suggests that male partners may be reinfecting women with BV-associated bacteria (henceforth referred to as BV-organisms) and impacting on the efficacy of treatment approaches solely directed to women. This trial aims to determine the effect of concurrent male partner treatment for preventing BV recurrence compared to current standard of care. METHODS: StepUp is an open-label, multicentre, parallel group randomised controlled trial for women diagnosed with BV and their male partner. Women with clinical-BV defined using current gold standard diagnosis methods (≥3 Amsel criteria and Nugent score (NS) = 4-10) and with a regular male partner will be assessed for eligibility, and couples will then be consented. All women will be prescribed oral metronidazole 400 mg twice daily (BID) for 7 days, or if contraindicated, a 7-day regimen of topical vaginal 2% clindamycin. Couples will be randomised 1:1 to either current standard of care (female treatment only), or female treatment and concurrent male partner treatment (7 days of combined antibiotics - oral metronidazole tablets 400 mg BID and 2% clindamycin cream applied topically to the glans penis and upper shaft [under the foreskin if uncircumcised] BID). Couples will be followed for up to 12 weeks to assess BV status in women, and assess the adherence, tolerability and acceptability of male partner treatment. The primary outcome is BV recurrence defined as ≥3 Amsel criteria and NS = 4-10 within 12 weeks of enrolment. The estimated sample size is 342 couples, to detect a 40% reduction in BV recurrence rates from 40% in the control group to 24% in the intervention group within 12 weeks. DISCUSSION: Current treatments directed solely to women result in unacceptably high rates of BV recurrence. If proven to be effective the findings from this trial will directly inform the development of new treatment strategies to impact on BV recurrence. TRIAL REGISTRATION: The trial was prospectively registered on 12 February 2019 on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000196145, Universal Trial Number: U1111-1228-0106, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376883&isReview=true ).

Step-up, step-down mental health care service: evidence from Western Australia's first - a mixed-method cohort study.

BACKGROUND: Mental health Step-up, Step-down services (SUSD), also known as subacute services or Prevention and Recovery Services, have emerged to fill an identified gap between hospital-based inpatient care and clinical community-based mental health support. Evidence for the effectiveness of the SUSD service model is limited but growing. Accordingly, this study looked to add to the extant body of knowledge, by (i) assessing change outcomes in mental health and wellbeing, and predictors of these changes, for patients who accessed Western Australia's first SUSD service; and (ii) evaluating patients' satisfaction with service, and what patients value from their stay. METHODS: This was a mixed-method retrospective cohort study. Participants comprised 382 patients who accessed a 22-bed Mental Health SUSD facility and incurred 551 episodes of care during the 01/07/2014-30/06/2016 period. Patients' change outcomes in psychological distress, general self-efficacy, and work and social adjustment from service entry to service exit were analyzed using generalized linear modeling. Simple Pearson's correlation coefficients were calculated for preliminary assessment of the associations between patients' service satisfaction and their change outcomes. Qualitative outcomes that patients valued from their stay were analyzed thematically according to a semi-grounded theoretical approach. RESULTS: Significant improvements were observed in patients' self-reported psychological distress, self-efficacy, and work and social adjustment (all p < 0.0001). A strong and persistent baseline effect existed across the three measures. Older age, female gender, and having a dependent child in the same household were protective/enhancing factors for the patients' recovery. Satisfaction with service was high. Patients valued having the time and space to recuperate, gain insight, focus, and create changes in their lives. CONCLUSION: The encouraging findings, regarding both patients' change outcomes and satisfaction with service, support the value of the SUSD service model for patients with mental illnesses. Strengths and limitations were discussed; ensued recommendations were offered to both service providers and researchers to enhance the robustness of future research findings, to help inform more effective policy and funding decisions related to mental health care.

Small differences in tibial contact locations following kinematically aligned TKA from the native contralateral knee.

PURPOSE: Kinematically aligned (KA) TKA strives to restore native limb and knee alignments without ligament release with the premise that knee function likewise will be closely restored to native to the extent enabled by the components used. This study determined differences in anterior-posterior (AP) tibial contact locations of a KA TKA performed with asymmetric, fixed bearing, posterior cruciate-retaining (PCR) components from those of the native contralateral knee and also determined the incidence of posterior rim contact of the tibial insert during a deep knee bend and a step-up. METHODS: Both knees were imaged using single-plane fluoroscopy for 25 patients with a calipered KA TKA and a native knee in the contralateral limb. AP tibial contact locations in each compartment were determined following 3D model-to-2D image registration. Differences in mean AP tibial contact locations in each compartment between the KA TKA knees and the native contralateral knees were analysed. Contact locations either on or beyond the most posterior point of the tibial insert determined the occurrence of posterior rim contact. RESULTS: Mean AP tibial contact locations for both native and KA TKA knees remained relatively centred in the medial compartment but moved posterior in the lateral compartment during flexion. In both the medial and lateral compartments, differences in mean AP tibial contact locations between the KA TKA knees and the native contralateral knees were more posterior and greatest at 0° flexion for both activities (4 mm, p = 0.0009 and 7 mm, p < 0.0001 for deep knee bend and 6 mm, p < 0.0001 and 8 mm, p < 0.0001 for step-up in the medial and lateral compartments, respectively). The incidence of posterior rim contact of the tibial insert was 16% (4 of 25 patients) but the lowest Oxford Knee Score was 43 for these patients. The median Oxford Knee Score for all patients was 46 (out of 48). CONCLUSIONS: Calipered KA TKA with asymmetric, fixed bearing, PCR components resulted in mean AP tibial contact locations which were relatively centred in the compartments and differed at most from those of the native contralateral knee by approximately 15% of the AP dimension of a mid-sized tibial baseplate. Although posterior rim contact occurred in some patients, all such patients had high patient-reported outcome scores. LEVEL OF EVIDENCE: Therapeutic, Level III.