Register Access Research Articles

Economic Benefits of Switching From Intravenous to Subcutaneous Epoetin Alfa for the Management of Anemia in Hemodialysis Patients.

Background:Erythropoiesis-stimulating agents including epoetin alfa have been a mainstay of anemia management in patients with chronic kidney disease. Although the standard practice has been to administer epoetin alfa to patients on hemodialysis (HD) intravenously (IV), subcutaneous (SQ) epoetin alfa is longer acting and achieve the same target hemoglobin level to be maintained at a reduced dose and cost.Objective:The primary objective of this study was to determine the economic benefits of change in route of epoetin alfa administration from IV to SQ in HD patients. The secondary objectives were (1) to determine the differences in epoetin alfa doses at the pre-switch (IV) and post-switch period (SQ) and (2) to determine serum hemoglobin concentration, transferrin saturation, ferritin level, IV iron dose and cost in relationship to route of epoetin alfa administration.Design:This retrospective observational study included patients who transitioned from IV to SQ epoetin alfa.Setting:Two HD sites in southern Saskatchewan (Regina General Hospital, and Wascana Dialysis Unit, Regina) and 2 sites in northern Saskatchewan (St. Paul’s [SPH] Hospital, and SPH Community Renal Health Center, Saskatoon).Patients:The study includes 215 patients who transitioned from IV to SQ and were alive at the end of 12-month follow-up period.Measurements:We calculated the dose and cost of different routes of epoetin alfa administration/patient month. Also, serum hemoglobin, markers of iron stores (transferrin saturation and ferritin), IV iron dose, and cost were determined in relation to route of epoetin alfa administration.Methods:Data were gathered from 6 months prior (IV) to 12 months after switching treatment to SQ. The paired t-test and Wilcoxon signed-rank test were used to compare variables between pre-switch (IV) and post-switch (SQ) period.Results:The median cost (interquartile range) of epoetin alfa/patient-month decreased from (CAD508.3 [CAD349-CAD900.8]) pre-switch (IV) to (CAD381.2 [CAD247-CAD681]) post-switch (SQ) (P < .001), a decrease of 25%. The median epoetin alfa dose/patient-month reduced from (38 500 [25 714.3-64 166.5] international unit) pre-switch to (26 750.3 [17 362.6-48 066] IU) post-switch (P < .001), a decrease of 30.51%. The mean hemoglobin concentration (± standard deviation) for patients in both periods remained stable (103.3 ± 9.2 vs 104.3 ± 13.3 g/L, P = .34) and within the target range. There were no significant differences in transferrin saturation, ferritin, and IV iron dose and cost between the 2 study periods.Limitations:We were unable to consistently obtain information across all the sites on hospitalizations, inflammatory markers, nutritional status, and gastrointestinal bleeding. In addition, as our study sample was subject to survival bias, we cannot generalize our study results to other populations.Conclusions:We have shown that administering epoetin alfa SQ in HD patients led to a 30.51% reduction in dose and 25% reduction in cost while achieving equivalent hemoglobin levels. Given the cost sparing advantages without compromising care while achieving comparable hemoglobin levels, HD units should consider converting to SQ mode of administration.Trial registration:The study was not registered on a publicly accessible registry as it was a retrospective chart review and exempted from review by the Research Ethics Board of the former Regina Qu’Appelle Health Region.

Barriers to Peritoneal Dialysis in Saskatchewan Canada: Results From a Province-Wide Survey.

Background:Peritoneal dialysis (PD) is an underutilized, therapeutic option to in-center hemodialysis (HD), given its similar survival and clinical efficacy but provides lifestyle benefits and cost savings. Despite these advantages, PD prevalence rates remains below 20% in many Canadian jurisdictions.Objectives:The primary objective of this study was to identify and assess patient-perceived barriers to PD implementation in Saskatchewan. The secondary objectives were to examine variations in patient-perceived barriers to PD by dialysis units (main dialysis units vs satellite dialysis units) and specific challenges faced by First Nation patients residing on reserves.Design:A cross-sectional observational survey study.Setting:Two major centers (Regina and Saskatoon) and 5 associated satellite units attached to each center across the province of Saskatchewan.Patients:We approached all prevalent in-center HD patients across Saskatchewan, 366 (49%) agreed to participate in the study.Measurements:Self-reported barriers to PD were assessed using a 26-question survey which was created after engagement of our multidisciplinary team.Methods:We conducted a cross-sectional survey of 740 prevalent in-center HD patients within the province of Saskatchewan, Canada, from June 2018 to January 2019. Around 366 (49%) patients agreed to participate in the study. The questionnaire was designed to capture patients’ perceived barriers to PD. Descriptive statistics were used to present the data. Chi-square and Mann-Whitney U-test were used to compare the patients’ responses (main dialysis units vs satellite dialysis units, and First Nation reserves vs nonreserves).Results:Of the 366 patients who completed the survey, 284 met the eligibility criteria and were included in the analysis. Patient-reported satisfaction with current in-center HD care was the most common barrier to PD uptake (92%), followed by proximity to their HD unit (61%). A lack of understanding of the benefits/risks of PD, fear of family burden (54% each), and unwillingness to dialyze daily and to learn a new technique (51% each) were additional factors. Patients residing on reserves compared to nonreserve residents felt PD had a higher risk of infection compared to HD (54% vs 34%, P = .005), and felt PD led to suboptimal care (47% vs 31%, P = .021).Limitations:We used a nonstandardized locally derived questionnaire to quantify barriers, and this prevents inclusion of additional barriers than individual patients may consider important. Cross-sectional data can only be used as a snapshot. Only 366 patients agreed to participate, and the results cannot be generalized to 740 prevalent HD patients. We did not capture data on demographics (age, income, and literacy level), comorbidities, and dialysis vintage, which would have been helpful in interpretation of the results. We did not involve patients, carers, or patients of First Nations heritage, in the design of the survey and the study.Conclusions:The results of our survey indicate that the major patient-reported barrier to PD uptake in our province is clinical inertia in patients defaulted to in-center HD at the onset of dialysis. Lack of patient awareness and knowledge of PD as a viable treatment modality also figured prominently, as did fears/concerns surrounding the safety, efficacy, and perceived family burden with PD compared with in-center HD.Trial Registration:The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.

Highly Concurrent Latency-tolerant Register Files for GPUs

Graphics Processing Units (GPUs) employ large register files to accommodate all active threads and accelerate context switching. Unfortunately, register files are a scalability bottleneck for future GPUs due to long access latency, high power consumption, and large silicon area provisioning. Prior work proposes hierarchical register file to reduce the register file power consumption by caching registers in a smaller register file cache. Unfortunately, this approach does not improve register access latency due to the low hit rate in the register file cache. In this article, we propose the Latency-Tolerant Register File (LTRF) architecture to achieve low latency in a two-level hierarchical structure while keeping power consumption low. We observe that compile-time interval analysis enables us to divide GPU program execution into intervals with an accurate estimate of a warp’s aggregate register working-set within each interval. The key idea of LTRF is to prefetch the estimated register working-set from the main register file to the register file cache under software control, at the beginning of each interval, and overlap the prefetch latency with the execution of other warps. We observe that register bank conflicts while prefetching the registers could greatly reduce the effectiveness of LTRF. Therefore, we devise a compile-time register renumbering technique to reduce the likelihood of register bank conflicts. Our experimental results show that LTRF enables high-capacity yet long-latency main GPU register files, paving the way for various optimizations. As an example optimization, we implement the main register file with emerging high-density high-latency memory technologies, enabling 8× larger capacity and improving overall GPU performance by 34%.

Explaining the global spatial distribution of organic crop producers

Organic farming has been proposed as a feasible way to reduce the environmental impacts of agriculture, provide better products to consumers, and improve farmers' income. How organic farmers are distributed worldwide, however, remains unknown. Using publicly accessible registries of organic crop farmers we mapped their distribution globally and related it to local socio-economic, climatic, and soil characteristics. We show that organic crop farmers are mostly present in areas with favorable socio-economic and climatic conditions, both globally but also within countries. Within developed countries, the locations of organic crop farmers often do not differ significantly from the locations of conventional crop farmers. In developing countries, there are, however, larger differences and organic crop farmers concentrate in the more accessible and developed regions. Our results suggest that crop farmers in poor areas may not have sufficient access to certification and markets. To promote the spread of organic farming, certification and other incentives could target farmers in areas with lower market access and higher levels of poverty which could improve value chains for organic products in these areas.

Why We Fail to Catch Money Launderers 99.9 Percent of the Time

The fight against money laundering in Canada will require tougher measures that shine a light on the perpetrators who now operate in the shadows, says a new report from the C.D. Howe Institute. In “Why We Fail to Catch Money Launderers 99.9 percent of the Time,” author Kevin Comeau supports the creation of a publicly accessible registry of beneficial ownership, and mandatory declarations of beneficial ownership with meaningful sanctions for false declarations.

What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review.

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps.Materials and Methods: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV.Results: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials.Conclusions: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.

Human leukocyte antigen-matched unrelated donor search experience for hematological disorder patients requiring transplant: scenario for Indian patients

Abstract Introduction: Human leukocyte antigen (HLA)-matched unrelated donor (MUD) is the source of MUD transplantation (MUDT) for about 70% of patients who do not have matched related donor. To facilitate MUD search globally, there are 75 stem cell registries with more than 28 million donors registered (as of January 2017). Out of these donors, India has an insignificant representation of approximately 0.23 million. Further, Indians express high genetic variations, making it difficult to find MUD for an Indian patient. Aims and Objectives: The aim of this study is to analyze the MUD search for hematological disorder patients requiring transplant. An attempt was made to observe the MUD scenario for Indian patients requiring MUDT from accessible stem cell registries. Methods: A total of 558 patients approached Genebandhu registry and Chimera Transplant Research Foundation for MUD search over a period of 4 years requiring MUDT were included in this study. High resolution of HLA-A, -B, -C, -DRB1, and -DQB1 was used to perform MUD search through proprietary software called Prometheus and Bone Marrow Donors Worldwide (BMDW) search tool. Results: Out of 558 patients, MUD was located only for 135 (24.19%) patients. Out of these 135 patients, 91 (16.30%) patients found an MUD in global database and only 44 (7.88%) patients within India. Conclusion: This study demonstrates that building a large Indian database will not only help in increasing the chances of finding an MUD for maximum number of patients within India but also provide cost-effective treatment, in a society where cost is a vital factor.

Scratch That (But Cache This): A Hybrid Register Cache/Scratchpad for GPUs

Graphics processing units (GPUs) are throughput-oriented architectures that implement massive multithreading. Large, power-hungry register files are required in GPUs to support the simultaneous execution of thousands of threads on the hardware. Prior work proposed reducing register access energy by adding a small register cache (RC) to the GPU. The cache stores recently referenced registers and services subsequent accesses to these registers, reducing accesses to the main register file. Later work obtained further energy savings by replacing this cache with a compiler-managed scratchpad. We note that registers are allocated to the cache dynamically and reactively whereas registers are allocated to the scratchpad statically and proactively. Our insight is that these allocation schemes are complimentary because the cache leverages runtime information unavailable to the compiler and the scratchpad leverages compile time information unavailable to the cache. Further, there exist register access patterns that are easily captured by one structure but for which the other structure is ineffective. Instead of implementing either an RC or scratchpad alone, we propose dividing temporary register storage capacity between a cache and a scratchpad in order to capture a broader range of register accesses. Given 12 KB of storage per streaming multiprocessor, our hybrid design reduces register energy to 38.7% of the baseline, compared to 47.9% for a RC and 47.1% for a register scratchpad.

Hidden Beneficial Ownership and Control: Canada as a Pawn in the Global Game of Money Laundering

Official estimates of money laundering in Canada range from $5 billion to $100 billion. Offences such as drug trafficking, fraud, tax evasion, smuggling and corruption are fuelling the laundering of dirty money. While many methods and techniques may be used to hide ill-gotten gains from tax authorities and police, launderers often use corporations and trusts to co-mingle dirty money with legitimate funds to flow them through these entities’ bank accounts or brazenly use the entity to exclusively conduct illegal activities. The “secret sauce” in this recipe is the creation of legal arrangements that hide the beneficial owner of the corporation, partnership or trust that exercises significant control over the entity. Indeed, with professional knowhow, complex structures can be created in Canada, or offshore, that will slow down or stop any intrepid investigator trying to connect the dirty money to the beneficial owner. The focus of this Commentary is to show how the lack of beneficial ownership transparency facilitates the use of corporations and trusts for illicit purposes. At present, there are no requirements to disclose beneficial ownership when creating a corporation. Nominee shareholders and directors can be appointed without disclosing the ultimate beneficial owner or the nominator. For trusts, there are also no requirements to identify the parties when registering. As a result, Canada fares poorly on international standards for disclosing beneficial ownership. Lack of beneficial ownership transparency is not only a structural flaw in Canada’s corporate registration system (federally, provincially and territorially) and, consequently, in its anti-money laundering and anti-terrorist financing measures, but it paints Canada as an international laggard and as a financial-secrecy jurisdiction. However, there now is a global momentum, led by the Europeans, to make beneficial ownership registries accessible to the public, and trusts under certain conditions, to more effectively address the threats posed by money laundering, terrorist financing, corruption and tax evasion. This Commentary’s recommendations are for the federal government, in collaboration with the provinces and territories, to establish a central publicly accessible beneficial ownership registry of corporations and certain trusts; require all reporting entities under the Proceeds of Crime (Money Laundering) and Terrorist Financing Act to identify beneficial ownership information; place the onus on corporations and trusts to truthfully and fully disclose beneficial ownership information; and follow the European example by keeping Canada current with the international standards, commitments and trends on beneficial ownership transparency.

Legal Protection on the Right of Geographical Indication for Micro and Small Business in Indonesia

Geographical indication is a part of intellectual property rights. Indonesia has the model of legal protection on it. But many unfair competitions that come from other country, espesially it is called passing of through international market. Actually there is several international convention provisions that regulate Geographical Indication covering international registration system. The methods of this research is normative, that based on doctrinal legal research. The research result shows that Indonesian law does not provide preventive protection for the citizens in terms of product registration even though product registration is the main requirement for a product to be given exclusive right when it is exported to another country so that passing off as a form of unfair competition can be avoided. Therefore, the government’s role in improving citizens’ awareness on the importance of exclusive right should be improved. Moreover, the government should ease the product registration access so that the product is able to compete in international market and should expand bilateral as well as multilateral cooperation.

S138. AN INVESTIGATION INTO THE ASSOCIATION BETWEEN EXPOSURE TO PRENATAL STRESS AND RISK OF PSYCHOSIS IN OFFSPRING

BackgroundExisting literature suggests that prenatal stress may be a risk factor for offspring psychiatric disorders. For example, large ecological studies have found that those exposed to stressors during gestation, such as war and famine, have a twofold increase risk of schizophrenia, as well as an increased risk for other affective disorders. Similarly, it was found that exposure to stressful events during pregnancy, such as the death of a relative during first trimester, increases the odds of the offspring developing schizophrenia in adulthood. In this study, our aim was to assess in a birth cohort, whether those who were exposed to prenatal stress were at higher odds for developing psychosis and other psychiatric disorders.MethodsUsing the Helsinki temperament cohort, a yearlong birth cohort with data collected from pregnancy onwards, logistic regressions were run examining perceived prenatal stress as a risk factor for psychosis and other psychiatric disorders. The exposure (prenatal stress) was measured using prenatal questionnaires which were given to pregnant women at antenatal clinic visits if birth was expected between 1st July 1975 and 30th June 1976. Psychiatric outcomes were assessed using linkage between the Finnish population register and the Finnish hospital discharge register in 2005.ResultsIn total, 3660 pregnant women submitted at least one prenatal questionnaire with the mean number of prenatal questionnaires submitted per woman being 6. At the point of register access, 226 individuals had either an ICD 8, 9 or 10 diagnoses, 72 diagnosed with a psychosis disorder. It was found that those exposed to prenatal stress were at a greater risk of developing psychosis (OR = 1.54, 95% CI = 0.78 – 3.05).DiscussionOur findings are in line with the current literature indicating a higher risk of psychosis among those exposed to perceived prenatal stress.

LTRF

Graphics Processing Units (GPUs) employ large register files to accommodate all active threads and accelerate context switching. Unfortunately, register files are a scalability bottleneck for future GPUs due to long access latency, high power consumption, and large silicon area provisioning. Prior work proposes hierarchical register file, to reduce the register file power consumption by caching registers in a smaller register file cache. Unfortunately, this approach does not improve register access latency due to the low hit rate in the register file cache. In this paper, we propose the Latency-Tolerant Register File (LTRF) architecture to achieve low latency in a two-level hierarchical structure while keeping power consumption low. We observe that compile-time interval analysis enables us to divide GPU program execution into intervals with an accurate estimate of a warp's aggregate register working-set within each interval. The key idea of LTRF is to prefetch the estimated register working-set from the main register file to the register file cache under software control, at the beginning of each interval, and overlap the prefetch latency with the execution of other warps. Our experimental results show that LTRF enables high-capacity yet long-latency main GPU register files, paving the way for various optimizations. As an example optimization, we implement the main register file with emerging high-density high-latency memory technologies, enabling 8X larger capacity and improving overall GPU performance by 31% while reducing register file power consumption by 46%.

Mining and clustering service goals for RESTful service discovery

In recent years, RESTful services that are mainly described using short texts are becoming increasingly popular. The keyword-based discovery technology adopted by existing service registries usually suffers from low recall and is insufficient to retrieve accurate RESTful services according to users’ functional goals. Moreover, it is often difficult for users to specify queries that can precisely represent their requirements due to the lack of knowledge on their desired service functionalities. Toward these issues, we propose a RESTful service discovery approach by leveraging service goal (i.e., service functionality) knowledge mined from services’ textual descriptions. The approach first groups the available services into clusters using probabilistic topic models. Then, service goals are extracted from the textual descriptions of services and also clustered based on the topic modeling results of services. Based on service goal clusters, we design a mechanism to recommend semantically relevant service goals to help users refine their initial queries. Relevant services are retrieved by matching user selected service goals with those of candidate services. To improve the recall of the goal-based service discovery approach, we further propose a hybrid approach by integrating it with two existing service discovery approaches. A series of experiments conducted on real-world services crawled from a publicly accessible registry, ProgrammableWeb, demonstrate the effectiveness of the proposed approaches.

Velocity of orthodontic active space closure with and without photobiomodulation therapy: a single-center, cluster randomized clinical trial

The objective of this two-arm, parallel randomized clinical trial was to assess the effectiveness of low-level light therapy (photobiomodulation) using an intraoral light-emitting diode (LED) device with respect to accelerating premolar extraction space closure during en masse retraction. This trial was conducted between January 2013 and February 2014 at the European Univeristy College Department of Orthodontics. The study included 60 orthodontic patients (age range, 11.3–47.1 years; mean age, 20.4 years) with premolar extractions. Patients (n = 60) were randomized into the photobiomodulation (PBM) group (n = 30) or the control group (n = 30). Eligibility criteria included no active caries, good oral hygiene, and an extraction orthodontic treatment plan. Extraction spaces were closed using NiTi closed springs utilizing 150 g of force. Extraction spaces were measured on study models at the beginning of en masse retraction (T1) and at space closure completion (T2). All measurements were obtained by a single investigator who was blinded to the group allocation of study models. The primary outcome was the velocity of extraction space closure (mm/month) during the period of en masse retraction. Treatment allocation was implemented using randomization with 2 major blocks of 30 patients, by asking each patient to draw a sealed envelope (n = 60) indicating allocation to the PBM or control group. The allocation ratio was 1:1. The PBM group of patients (n = 30) was treated with intraoral infrared LED light therapy for 3 min per arch per day using OrthoPulse™ (Biolux Research®, Vancouver, Canada) producing a continuous 850-nm wavelength and a power density of 33 mW/cm2 per arch per day to achieve a total energy density of approximately 6 J/cm2 at the surface of the device during the en masse retraction phase; patients were required to maintain over 80% compliance with daily device use. Compliance was monitored by the device controller’s onboard computer. Sixty patients were randomized between the two groups. Fifteen patients dropped out during the study period, but were accounted for in the primary analysis as an intention to treat (ITT) analysis through multiple imputations. Mean age for the PBM and control groups were 20.7 and 22 years, respectively. Patients treated with PBM exhibited a statistically significant higher velocity of space closure by 0.22 mm/month (95% confidence interval [CI], 0.09–0.49; p < 0.01). The mean velocity of space closure in the PBM group was 1.08 mm/month (SD 0.54) compared with the control group’s 0.86 mm/month (SD 0.42). A secondary analysis was conducted on the 45 patients that reached the primary outcome and did not deviate from the study protocol (15 dropout patients removed), providing 123 extraction spaces for the analysis—23 patients from the PBM group and 22 patients from the control group. No serious harms due to treatments were encountered during the study period. The results of this study suggest that PBM therapy accelerated the rate of orthodontic space closure during en masse retraction. This trial and its protocol were not registered on a publicly accessible registry.

The Design of IP Core for LCD Controller Based on SOPC

In this paper, it introduces the design and implementation of custom IP core for liquid crystal display (LCD) controller based on system on a programmable chip (SOPC) technology and Verilog hardware description language (HDL). The IP core can be put up as a general-purpose peripheral module to the Avalon Bus, communicating with the NIOS II through registers, and the underlying sequential logic for communicating with the external LCD liquid crystal module is automatically completed by the module. The driver does not need to care about the details of the underlying timing, it only needs to implement the read and write operations of the LCD data through register access, thus achieve the purpose of controlling the display content of the LCD. In addition to reducing the complexity of driver development, the design can also take full advantage of the parallel operation of hardware logic to improve the execution efficiency of the entire system and the throughput of processing tasks, especially in some occasions where high-speed image real-time processing is required. Simulations and experiments show that the IP core for LCD controller has good stability, versatility and compatibility.

Trials of transvaginal mesh devices for pelvic organ prolapse: a systematic database review of the US FDA approval process

IntroductionTransvaginal mesh devices are approved in the USA by the Food and Drug Administration (FDA), through the 510(k) system. However, there is uncertainty about the benefit to harm balance of...

Split Latency Allocator: Process Variation-Aware Register Access Latency Boost in a Near-Threshold Graphics Processing Unit

Split Latency Allocator: Process Variation-Aware Register Access Latency Boost in a Near-Threshold Graphics Processing Unit

Psychosocial and career outcomes of peer mentorship in medical resident education: a systematic review protocol

BackgroundMany medical residents lack ready access to social and emotional supports that enable them to successfully cope with the challenges associated with medical residency. This absence of support has been shown to lead to high levels of burnout, decreased mental wellbeing, and difficulty mastering professional competencies in this population. While there is emerging evidence that peer mentoring can be an important source of psychosocial and career-related support for many individuals, the extent of the evidence regarding the benefits of peer mentorship in medical residency education has not yet been established. We describe a protocol for a systematic review to assess the effects of peer mentoring on medical residents’ mental wellbeing, social connectedness, and professional competencies.MethodsStudies included in this review will be those that report on peer-mentoring relationships among medical residents. Quantitative, qualitative, and mixed-methods studies will be eligible for inclusion. No date or language limits will be applied. We will search EMBASE, MEDLINE, PsychINFO, Web of Science, Scopus, ERIC, Education Research Complete, and Academic Research Complete databases to identify relevant studies. Two authors will independently assess all abstracts and full-text studies for inclusion and study quality and extract study data in duplicate.DiscussionThis is the first systematic review to explicitly explore the role of peer mentoring in the context of medical residency education. We anticipate that the findings from this review will raise awareness of the benefits and challenges associated with peer-mentoring relationships, further the development and implementation of formal peer-mentoring programs for medical residents, and, through identifying gaps in the existing literature, inform future research efforts.Systematic review registrationThis protocol has not been registered in PROSPERO or any other publicly accessible registry.

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting

ObjectivesThe decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. Study Design and SettingWe identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. ResultsWe identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. ConclusionDespite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding.

Leflunomide is equally efficacious and safe compared to low dose rituximab in refractory rheumatoid arthritis given in combination with methotrexate: results from a randomized double blind controlled clinical trial

BackgroundThe standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination.MethodsPatients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly assigned to rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. Sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, tetanus and pneumococcal antibody levels were secondary end points.ResultsBaseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84% (p = 0.93), ACR50 was 60% vs. 64% (p = 0.79) and ACR70 was 35% vs 32% (P = 0.84), in rituximab and in leflunomide groups respectively. Serious adverse events were similar.With rituximab there was significant reduction in B cells (p < 0.001), memory B cells (p < 0.001) and pneumococcal antibody levels (P < 0.05) without significant changes in T cells (p = 0.835) and tetanus antibody levels (p = 0.424) at 24 weeks. With leflunomide, significant reduction in memory B cells (p < 0.01) and pneumococcal antibody levels (p < 0.01) occurred without significant changes in B cells (P > 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05).ConclusionsLeflunomide-methotrexate combination is as efficacious as low-dose rituximab-methotrexate combination at 24 weeks, in RA patient’s refractory to initial DMARDs. The high responses seen in both groups have favorable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterization.Trial registrationThe trial was registered with the Sri Lanka Clinical Trials Registry (SLCTR), a publicly accessible primary registry linked to the registry network of the International Clinical Trials Registry Platform of the WHO (WHO-ICTRP) (registration number: SLCTR/2008/008 dated 16th May 2008).