Long-term disability trajectories in multiple sclerosis: a group-based trajectory analysis of the AusLong cohort.

BACKGROUND: Previous natural history studies highlighted a consistent heterogeneity of disability trajectories among individuals with primary or secondary progressive multiple sclerosis (MS). However, evidence on disability progression in relapsing onset MS is scarce.The aim of this study was to investigate heterogeneity in disability accumulation over 10 years following a first clinical diagnosis of central nervous system demyelination (FCD) and identify genetic, demographic, environmental and clinical factors associated with these trajectories. METHODS: We used group-based trajectory models to measure heterogeneity in disability trajectories based on the Expanded Disability Status Scale (EDSS) in a prospectively assessed cohort of 263 participants. To capture sustained neurological impairments and avoid issues related to significant changes in EDSS associated with relapse, we did not consider EDSS points recorded within 3 months of a relapse. RESULTS: We identified three distinct and clinically meaningful disability trajectories: No/minimal, moderate and severe. Those in the no/minimal disability trajectory showed no appreciable progression of disability (median EDSS∼1 at 10-year review) while those in the moderate and severe disability trajectories experienced disability worsening (median time to reach EDSS 4 was 9 and 7 years, respectively). Compared with the no/minimal disability trajectory, those with older age, a higher number of relapses within the first 5 years post-FCD, and a higher number of comorbidities at baseline were more likely to be in the worse disability trajectory. Surprisingly, baseline MRI and anatomical site of initial symptoms did not influence long-term outcomes. CONCLUSIONS: Those at higher risk of faster MS disability progression can be identified based on their early clinical characteristics with potential therapeutic implications for early intervention and treatment escalation.

Stapled Anastomosis Versus Hand-Sewn Anastomosis With Mucosectomy for Ileal Pouch-Anal Anastomosis: A Systematic Review and Meta-analysis of Postoperative Outcomes, Functional Outcomes, and Oncological Safety.

PURPOSE: This systematic review and meta-analysis aimed to compare outcomes between stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA with mucosectomy in cases of ulcerative colitis and familial adenomatous polyposis. METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines 2020 and AMSTAR 2 (Assessing the methodological quality of systematic reviews) guidelines. We included randomized clinical trials (RCTs) and controlled clinical trials (CCTs). Subgroup analysis was performed according to the indication for surgery. RESULTS: The bibliographic research yielded 31 trials: 3 RCTs, 5 prospective clinical trials, and 24 CCTs including 8872 patients: 4871 patients in the stapled group and 4038 in the hand-sewn group. Regarding postoperative outcomes, the stapled group had a lower rate of anastomotic stricture, small bowel obstruction, and ileal pouch failure. There were no differences between the 2 groups in terms of operative time, anastomotic leak, pelvic sepsis, pouchitis, or hospital stay. For functional outcomes, the stapled group was associated with greater outcomes in terms of seepage per day and by night, pad use, night incontinence, resting pressure, and squeeze pressure. There were no differences in stool Frequency per 24h, stool frequency at night, antidiarrheal medication, sexual impotence, or length of the high-pressure zone. There was no difference between the 2 groups in terms of dysplasia and neoplasia. CONCLUSIONS: Compared to hand-sewn anastomosis, stapled ileoanal anastomosis leads to a large reduction in anastomotic stricture, small bowel obstruction, ileal pouch failure, seepage by day and night, pad use, and night incontinence. This may ensure a higher resting pressure and squeeze pressure in manometry evaluation. PROTOCOL REGISTRATION: The protocol was registered at PROSPERO under CRD 42022379880.

Non-Enzymatic Glucose Sensors Composed of Polyaniline Nanofibers with High Electrochemical Performance.

The measurement of glucose concentration is a fundamental daily care for diabetes patients, and therefore, its detection with accuracy is of prime importance in the field of health care. In this study, the fabrication of an electrochemical sensor for glucose sensing was successfully designed. The electrode material was fabricated using polyaniline and systematically characterized using scanning electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and UV-visible spectroscopy. The polyaniline nanofiber-modified electrode showed excellent detection ability for glucose with a linear range of 10 µM to 1 mM and a detection limit of 10.6 µM. The stability of the same electrode was tested for 7 days. The electrode shows high sensitivity for glucose detection in the presence of interferences. The polyaniline-modified electrode does not affect the presence of interferences and has a low detection limit. It is also cost-effective and does not require complex sample preparation steps. This makes it a potential tool for glucose detection in pharmacy and medical diagnostics.

Comprehensive Case-Control Study of Protective and Risk Factors for Buruli Ulcer, Southeastern Australia.

To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.

Affordability of newer antiseizure medications in Asian resource-limited countries.

OBJECTIVE: One of the objectives of the Intersectoral Global Action Plan on epilepsy and other neurological disorders for 2022 to 2031 is to ensure at least 80% of people with epilepsy (PWE) will have access to appropriate, affordable, and safe antiseizure medications (ASMs) by 2031. However, ASM affordability is a significant issue in low- and middle-income countries, preventing PWE from accessing optimal treatment. This study aimed to determine the affordability of the newer (second and third generation) ASMs in resource-limited countries in Asia. METHODS: We conducted a cross-sectional survey by contacting country representatives in lower-middle-income countries (LMICs) in Asia, including Indonesia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Vietnam, India, Bangladesh, and Pakistan, and the upper-middle-income country Malaysia, from March 2022 to April 2022. The affordability of each ASM was calculated by dividing the 30-day ASM cost by the daily wage of the lowest paid unskilled laborers. Treatment costing 1 day's wage or less for a 30-day supply of chronic disease is considered affordable. RESULTS: Eight LMICs and one upper-middle-income country were included in this study. Lao PDR had no newer ASM, and Vietnam had only three newer ASMs. The most frequently available ASMs were levetiracetam, topiramate, and lamotrigine, and the least frequently available was lacosamide. The majority of the newer ASMs were unaffordable, with the median number of days' wages for a 30-day supply ranging from 5.6 to 14.8 days. SIGNIFICANCE: All new generation ASMs, whether original or generic brands, were unaffordable in most Asian LMICs.

Delorme's vs. Altemeier's in the management of rectal procidentia: systematic review and meta-analysis.

BACKGROUND: Rectal prolapse is a distressing condition for patients and no consensus exists on optimal surgical management. We compared outcomes of two common perineal operations (Delorme's and Altemeier's) used in the treatment of rectal prolapse. METHODS: A systematic search of multiple electronic databases was conducted. Peri- and post-operative outcomes following Delorme's and Altemeier's procedures were extracted. Primary outcomes included recurrence rate, anastomotic dehiscence rate and mortality rate. The secondary outcomes were total operative time, volume of blood loss, length of hospital stay and coloanal anastomotic stricture formation. Revman 5.3 was used to perform all statistical analysis. RESULTS: Ten studies with 605 patients were selected; 286 underwent Altemeier's procedure (standalone), 39 had Altemeier's with plasty (perineoplasty or levatoroplasty), and 280 had Delorme's. Recurrence rate [OR: 0.66; 95% CI [0.44-0.99], P = 0.05] was significantly lower and anastomotic dehiscence [RD: 0.05; 95% CI [0.00-0.09], P = 0.03] was significantly higher in the Altemeier's group. However, sub group analysis of Altemeier's with plasty failed to show significant differences in these outcomes compared with the Delorme's procedure. Length of hospital stay was significantly more following an Altemeier's operation compared with Delorme's [MD: 3.05, 95% CI [0.95 - 5.51], P = 0.004]. No significant difference was found in total operative time, intra-operative blood loss, coloanal anastomotic stricture formation and mortality rates between the two approaches. CONCLUSIONS: A direct comparison of two common perineal procedures used in the treatment of rectal prolapse demonstrated that the Altemeier's approach was associated with better outcomes. Future, well-designed high quality RCTs with long-term follow up are needed to corroborate our findings.

Single-incision versus multi-port laparoscopic ileocolic resections for Crohn's disease: Systematic review and meta-analysis.

Introduction: The aim of this systematic review and meta-analysis is to compare the outcomes of single-incision laparoscopic surgery (SILS) versus multi-port laparoscopy for ileocolic resection in patients with Crohn's disease (CD). Patients and Methods: A systematic search of multiple electronic databases was conducted. The peri- and post-operative outcomes were evaluated between Crohn's patients undergoing SILS versus multi-port laparoscopy for ileocolic resection. The primary outcomes included operative time, anastomotic leak rate, post-operative wound infections and length of hospital stay. Analysed secondary outcomes were conversion rates, ileus occurrence, intra-abdominal abscess formation, return to theatre and re-admissions. Revman 5.3 was used to perform the statistical analysis. Results: Five observational studies with 521 patients (SILS: 211; multi-port: 310) were included in the data synthesis. Patients undergoing SILS had a reduced total operative time compared to multi-port laparoscopy (mean difference [MD]: -16.14, 95% confidence interval: [CI] -27.23 - 5.05, P = 0.004). Post-operative hospital stay was also found to be significantly less in the SILS group (MD: -0.57, 95% CI: -0.73--0.42, P < 0.0001). No significant difference was seen in the anastomotic leak rate (MD: -16.14, 95% CI: 0.18-1.71, P = 0.004) or post-operative wound infections (odds ratio: 0.78, 95% CI: 0.24 - 2.47, P = 0.67) between the two groups. Moreover, all the measured secondary outcomes were comparable. Conclusion: SILS seems to be a feasible alternative to multi-port laparoscopic surgery for ileocolic resection in patients with CD. Improved outcomes in terms of total operative time and length of hospital stay were observed in patients undergoing SILS surgery. Adopting this procedure into routine clinical practice constitutes the next step in the development of minimally invasive surgery.

Comparison of Midline and Off-midline specimen extraction following laparoscopic left-sided colorectal resections: A systematic review and meta-analysis.

Aims: This study aims to evaluate comparative outcomes following midline versus off-midline specimen extractions following laparoscopic left-sided colorectal resections. Methods: A systematic search of electronic information sources was conducted. Studies comparing 'midline' versus 'off midline' specimen extraction following laparoscopic left-sided colorectal resections performed for malignancies were included. The rate of incisional hernia formation, surgical site infection (SSI), total operative time and blood loss, anastomotic leak (AL) and length of hospital stay (LOS) was the evaluated outcome parameters. Results: Five comparative observational studies reporting a total of 1187 patients comparing midline (n = 701) and off-midline (n = 486) approaches for specimen extraction were identified. Specimen extraction performed through an off-midline incision was not associated with a significantly reduced rate of SSI (odds ratio [OR]: 0.71; P = 0.68), the occurrence of AL (OR: 0.76; P = 0.66) and future development of incisional hernias (OR: 0.65; P = 0.64) compared to the conventional midline approach. No statistically significant difference was observed in total operative time (mean difference [MD]: 0.13; P = 0.99), intraoperative blood loss (MD: 2.31; P = 0.91) and LOS (MD: 0.78; P = 0.18) between the two groups. Conclusions: Off-midline specimen extraction following minimally invasive left-sided colorectal cancer surgery is associated with similar rates of SSI and incisional hernia formation compared to the vertical midline incision. Furthermore, there were no statistically significant differences observed between the two groups for evaluated outcomes such as total operative time, intra-operative blood loss, AL rate and LOS. As such, we did not find any advantage of one approach over the other. Future high-quality well-designed trials are required to make robust conclusions.

Long-term trajectories of employment status, workhours and disability support pension status, after a first episode of CNS demyelination.

BACKGROUND: People with multiple sclerosis face significant employment-related challenges, with little known of the drivers of these outcomes. OBJECTIVE: We examined prospective trajectories of employment-related outcomes up to 11 years following a first episode of central nervous system (CNS) demyelination (FCD). METHODS: Participants were aged 18-59 years, at FCD, with at least two observations and were employed at study entry or anytime during follow-up (n = 207). Outcomes were employment status (full-time, part-time and unemployed), average workhours per week and disability support pension (DSP; receiving/not receiving). We used group-based trajectory modelling to identify groups with common trajectories. Factors associated with trajectory membership were explored using log-multinomial regression. RESULTS: Distinct trajectories were identified for employment (4), workhours (4) and DSP (2). Compared with stable full-time, female sex was strongly associated with being in the stable part-time trajectory (risk ratio (RR): 5.35; 95% confidence interval (CI) = 2.56-11.20; p < 0.001). A greater level of disability at 5-year review (RR: 1.35; 95% CI = 1.19-1.53) and having more than two comorbidities at baseline (RR: 2.77; 95% CI = 1.37-5.64) were associated with being in early and late deteriorated employment trajectories, respectively. Compared with the increased part-time trajectory, every additional relapse during the 5 years post-FCD was associated with a 10% increased risk of being in the reduced part-time trajectory (RR = 1.10; 95%CI = 1.00-1.22). For every additional EDSS point at 5-year review, the risk of being in the DSP trajectory increased (RR = 1.21; 95% CI = 1.05-1.41). CONCLUSION: These trajectories indicate substantial heterogeneity and the complex impact of MS on employment from its earliest timepoints. Understanding these trends could enable better targeting of interventions to facilitate workforce retention, particularly for females, those with a higher number of comorbidities, more frequent relapses and greater rate of disability accrual.

Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study.

Objective: Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes. Approach and Results: Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34-expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3+/-2.4 pg/mL and 0.1+/-1.0 mg/L; P=0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, -0.17; P<0.001). Using linear regression, IL-6 and high-sensitivity CRP levels declined by -0.59 (95% CI, -0.90 to -0.20) pg/mL and -0.13 (-0.28 to 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables, as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95% CI, 9-13) greater risk of death/myocardial infarction. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts. Conclusions: Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes.

Multimorbidity, healthcare use and catastrophic health expenditure by households in India: a cross-section analysis of self-reported morbidity from national sample survey data 2017-18.

BACKGROUND: The purpose of this research is to generate new evidence on the economic consequences of multimorbidity on households in terms of out-of-pocket (OOP) expenditures and their implications for catastrophic OOP expenditure. METHODS: We analyzed Social Consumption Health data from National Sample Survey Organization (NSSO) 75th round conducted in the year 2017-2018 in India. The sample included 1,13,823 households (64,552 rural and 49,271 urban) through a multistage stratified random sampling process. Prevalence of multimorbidity and related OOP expenditure were estimated. Using Coarsened Exact Matching (CEM) we estimated the mean OOP expenditure for individuals reporting multimorbidity and single morbidity for each episode of outpatient visits and hospital admission. We also estimated implications in terms of catastrophic OOP expenditure for households. RESULTS: Results suggest that outpatient OOP expenditure is invariably lower in the presence of multimorbidity as compared with single conditions of the selected Non-Communicable Diseases(NCDs) (overall, INR 720 [USD 11.3] for multimorbidity vs. INR 880 [USD 14.8] for single). In the case of hospitalization, the OOP expenditures were mostly higher for the same NCD conditions in the presence of multimorbidity as compared with single conditions, except for cancers and cardiovascular diseases. For cancers and cardiovascular, OOP expenditures in the presence of multimorbidity were lower by 39% and 14% respectively). Furthermore, around 46.7% (46.674-46.676) households reported incurring catastrophic spending (10% threshold) because of any NCD in the standalone disease scenario which rose to 63.3% (63.359-63.361) under the multimorbidity scenario. The catastrophic implications of cancer among individual diseases was the highest. CONCLUSIONS: Multimorbidity leads to high and catastrophic OOP payments by households and treatment of high expenditure diseases like cancers and cardiovascular are under-financed by households in the presence of competing multimorbidity conditions. Multimorbidity should be considered as an integrated treatment strategy under the existing financial risk protection measures (Ayushman Bharat) to reduce the burden of household OOP expenditure at the country level.

Light-controlled growth factors release on tetrapodal ZnO-incorporated 3D-printed hydrogels for developing smart wound scaffold.

Advanced wound scaffolds that integrate active substances to treat chronic wounds have gained significant recent attention. While wound scaffolds and advanced functionalities have previously been incorporated into one medical device, the wirelessly triggered release of active substances has remained the focus of many research endeavors. To combine multiple functions including light-triggered activation, anti-septic, angiogenic, and moisturizing properties, we have developed a 3D printed hydrogel patch encapsulating vascular endothelial growth factor (VEGF) decorated with photoactive and antibacterial tetrapodal zinc oxide (t-ZnO) microparticles. To achieve the smart release of VEGF, t-ZnO was modified by chemical treatment and activated through UV/visible light exposure. This process would also make the surface rough and improve protein adhesion. The elastic modulus and degradation behavior of the composite hydrogels, which must match the wound healing process, were adjusted by changing t-ZnO concentrations. The t-ZnO-laden composite hydrogels can be printed with any desired micropattern to potentially create a modular elution of various growth factors. The VEGF decorated t-ZnO-laden hydrogel patches showed low cytotoxicity and improved angiogenic properties while maintaining antibacterial functions in vitro. In vivo tests showed promising results for the printed wound patches, with less immunogenicity and enhanced wound healing.

Changes in multiple sclerosis symptoms are associated with changes in work productivity of people living with multiple sclerosis.

BACKGROUND: While employment rates have increased in people with multiple sclerosis (PwMS), little is known about the longitudinal trends of work productivity. OBJECTIVE: To describe the longitudinal patterns of work productivity and examine the factors associated with annual change of work productivity of PwMS. METHODS: Study participants were employed participants of the Australian MS Longitudinal Study (AMSLS) followed from 2015 to 2019 with at least two repeated measures (n = 2121). We used linear mixed models to examine if the within-individual variations in MS symptoms are associated with changes in work productivity. RESULTS: The mean annual change in work productivity between 2015 and 2019 was -0.23% (SD = 18.68%). Not the actual severity of symptoms but rather the changes in severity of symptoms that are associated with change in work productivity in the same year. In a multivariable model, every unit increase in mean annual change in 'pain and sensory symptoms', 'feelings of anxiety and depression', and 'fatigue and cognitive symptoms' were independently associated with 2.43%, 1.55% and 1.01% annual reductions in work productivity, respectively. CONCLUSION: Individual changes in work productivity are largely driven by the changes in symptom severity rather than the absolute severity. Stabilising/improving MS symptoms might improve work productivity.

Comorbidity patterns in people with multiple sclerosis: A latent class analysis of the Australian Multiple Sclerosis Longitudinal Study.

BACKGROUND AND PURPOSE: This study was undertaken to identify clinically meaningful comorbidity patterns and their associations with the demographic/clinical characteristics of people with multiple sclerosis (MS). METHODS: We conducted latent class analysis to identify clinically distinct comorbidity patterns in MS using the 15 most common comorbidities among 1518 Australian Multiple Sclerosis Longitudinal Study participants. The associations between demographic/clinical characteristics and comorbidity patterns were examined using log-binomial and multinomial logistic regression. RESULTS: Five distinct comorbidity patterns were identified: "minimally diseased class" (30.8%), consisting of participants with no or one comorbidity; "metabolic class" (22.7%); "mental health-allergy class" (21.7%); "nonmetabolic class" (7.6%); and "severely diseased class" (7.0%), consisting of participants with higher prevalence of these comorbidities. The relative probabilities of being assigned to comorbidity classes compared to the minimally diseased class were significantly increased for participants who were older (metabolic: relative risk ratio [RRR] = 1.09, 95% confidence interval [CI] = 1.06-1.11; nonmetabolic: RRR = 1.07, 95% CI = 1.04-1.11; severely diseased: RRR = 1.04, 95% CI = 1.01-1.08), female (nonmetabolic: RRR = 5.35, 95% CI = 1.98-14.42; severely diseased: RRR = 2.21, 95% CI = 1.02-4.77), and obese (metabolic: RRR = 4.06, 95% CI = 2.45-6.72; mental health-allergy: RRR = 1.57, 95% CI = 1.00-2.46; severely diseased: RRR = 4.53, 95% CI = 2.21-9.29) and who had moderate disability (mental health-allergy: RRR = 2.32, 95% CI = 1.47-3.64; severely diseased: RRR = 2.65, 95% CI = 1.16-6.04). CONCLUSIONS: Comorbidity patterns exist in MS. Women, people who were older, people who were obese, and people who had higher disability levels were more likely to be in classes with higher levels of comorbidity. These findings may offer opportunities for designing more personalised approaches to comorbidity prevention and treatment.

Feasibility and safety of quantitative adenosine stress perfusion cardiac magnetic resonance imaging in pediatric heart transplant patients with and without coronary allograft vasculopathy.

BACKGROUND: Pediatric heart transplant patients require cardiac catheterization to monitor for coronary allograft vasculopathy. Cardiac catheterization has no safe and consistent method for measuring microvascular disease. Stress perfusion cardiac magnetic resonance imaging (MRI) assessing microvascular disease has been performed in adults. OBJECTIVE: To investigate the feasibility and safety of performing cardiac MRI with quantitative adenosine stress perfusion testing in pediatric heart transplant patients with and without coronary allograft vasculopathy. MATERIALS AND METHODS: All pediatric heart transplant patients with coronary vasculopathy at our institution were asked to participate. Age- and gender-matched pediatric heart transplant patients without vasculopathy were recruited for comparison. Patients underwent cardiac MRI with adenosine stress perfusion testing. RESULTS: Sixteen pediatric heart transplant patients, ages 6-22 years, underwent testing. Nine patients had vasculopathy by angiography. No heart block or other complications occurred during the study. The myocardial perfusion reserve for patients with vasculopathy showed no significant difference with comparison patients (median: 1.43 vs. 1.48; P=0.49). Values for both groups were lower than expected values based on previous adult studies. The patients were also analyzed for time after transplant and the number of rejection episodes. Patients within 6 years of transplantation had a nonsignificant trend toward a higher myocardial perfusion reserve (median: 1.57) versus patients with older transplants (median: 1.47; P=0.46). Intra- and interobserver reproducibility were 97% and 92%, respectively. CONCLUSION: Myocardial perfusion reserve is a safe and feasible method for estimating myocardial perfusion in pediatric heart transplant patients. There is no reliable way to monitor microvascular disease in pediatric patients. This method shows potential and deserves investigation in a larger cohort.

Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma.

Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.

An Adaptive Wake-Up-Interval to Enhance Receiver-Based Ps-Mac Protocol for Wireless Sensor Networks.

Many receiver-based Preamble Sampling Medium Access Control (PS-MAC) protocols have been proposed to provide better performance for variable traffic in a wireless sensor network (WSN). However, most of these protocols cannot prevent the occurrence of incorrect traffic convergence that causes the receiver node to wake-up more frequently than the transmitter node. In this research, a new protocol is proposed to prevent the problem mentioned above. The proposed mechanism has four components, and they are Initial control frame message, traffic estimation function, control frame message, and adaptive function. The initial control frame message is used to initiate the message transmission by the receiver node. The traffic estimation function is proposed to reduce the wake-up frequency of the receiver node by using the proposed traffic status register (TSR), idle listening times (ILTn, ILTk), and "number of wake-up without receiving beacon message" (NWwbm). The control frame message aims to supply the essential information to the receiver node to get the next wake-up-interval (WUI) time for the transmitter node using the proposed adaptive function. The proposed adaptive function is used by the receiver node to calculate the next WUI time of each of the transmitter nodes. Several simulations are conducted based on the benchmark protocols. The outcome of the simulation indicates that the proposed mechanism can prevent the incorrect traffic convergence problem that causes frequent wake-up of the receiver node compared to the transmitter node. Moreover, the simulation results also indicate that the proposed mechanism could reduce energy consumption, produce minor latency, improve the throughput, and produce higher packet delivery ratio compared to other related works.

Systematic review of acute pancreatitis associated with interferon-α or pegylated interferon-α: Possible or definitive causation?

BACKGROUND: Acute pancreatitis (AP) associated with interferon-α or pegylated interferon-α (AP-IFN) has been described, although the causal relation certitude remains elusive. Some recent studies suggest definite causality, although the relation is grouped in class III of Badalov classification of drug-induced AP. OBJECTIVES: Perform systematic review of AP-IFN and assess causality. METHODS: Two reviewers independently evaluated the data and quality of studies extracted from multiple databases on March 13, 2017. Studies selection was based on a priori criteria. Naranjo scale, and Badalov classification were applied to determine causality. RESULTS: We identified 16 studies that reported AP-IFN with a total of 23 patients. Fifteen studies had moderate to good methodological quality. The frequency of AP-IFN was 7/3450 (0.2%). The median age of patients was 50 years. In most cases IFN was used for chronic hepatitis C. The latency between IFN and diagnosis of AP was (>30 days). AP was mild or moderately severe and improved with supportive management. No mortality was observed. Re-challenge was done in 5 patients and resulted in AP recurrence in 3 cases. Twenty-one cases were classified as probable and 2 cases as definitive according to Naranjo scale. Evaluations of studies confirm a status Ia for AP-IFN according to Badalov classification. CONCLUSION: AP-IFN is rare and has a probable or definite causal relation according to Naranjo scale. The evidence supports a class Ia of Badalov classification. Hypertriglyceridemia is not a contributing factor. IFN-induced AP is usually mild or moderately severe, and responds favorably to supportive management.