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Objective: Using graph theoretical analysis, the current study explores network properties of highly associated brain areas during initiation and inhibition. Method: The current study utilized a publicly available dataset of functional connectivity matrices generated during initiation and inhibition (go/nogo paradigm) in 144 healthy adults between the age of 20 and 86 who were recruited from the greater Toronto area (Jenny R Rieck et. al, 2021). The researcher selected brain areas (ROIs) that showed high correlation (>0.75) from each participant's matrices and input high incidents of functional connectivity among all participants into an incidental matrix which was used to generate a network graph for each task. ROIs are presented as nodes (vertices) while their connections are edges. Core measures, such as degree distribution, mean distance, within module degree z score, and gateway coefficient, were analyzed. Results: The analysis showed a disconnected network across several brain regions and several common connections among somatomotor, default A, and peripheral visual networks. For the initiation task, the medial prefrontal cortex on both hemispheres are more frequently activated. A high betweenness was found in different brain areas for the inhibition and initiation across visual and default networks. Further analysis showed the extra-striate cortex appears to be the “hub” for initiation while the extra-striate superior cortex appears to be the “hub” for inhibition. Conclusion(s): The present study showed several common brain areas that are activated during both initiation and inhibition, highlighted differences in activation between the two tasks and explored several areas that could be a “hub” during each task.

Mental health nurses report experiencing stigmatization both from within and outside the profession, and associative stigma provides one way to explore that experience. To better understand the current state of the literature on mental health care professionals' experiences of associative stigma, and particularly on nurses' experience of this phenomenon, an integrative review of the literature on the subject was conducted. The results detail factors associated with associative stigma, the effects of associative stigma on nurses and caregivers of persons with mental illnesses, and the quantification of associative stigma. This article concludes by discussing implications for nursing practice, education, and research.

Bisphenol A (BPA) is an environmentally prevalent endocrine disrupting chemical that can impact human health and may be an environmental risk factor for neurodevelopmental disorders. BPA has been associated with behavioral impairment in children and a variety of neurodevelopmental phenotypes in model organisms. We used Drosophila melanogaster to explore the consequences of developmental BPA exposure on gene expression, cognitive function, and synapse development. Our transcriptome analysis indicated neurodevelopmentally relevant genes were predominantly downregulated by BPA. Among the misregulated genes were those with roles in learning, memory, and synapse development, as well as orthologs of human genes associated with neurodevelopmental and neuropsychiatric disorders. To examine how gene expression data corresponded to behavioral and cellular phenotypes, we first used a predator-response behavioral paradigm and found that BPA disrupts visual perception. Further analysis using conditioned courtship suppression showed that BPA impairs associative learning. Finally, we examined synapse morphology within the larval neuromuscular junction and found that BPA significantly increased the number of axonal branches. Given that our findings align with studies of BPA in mammalian model organisms, this data indicates that BPA impairs neurodevelopmental pathways that are functionally conserved from invertebrates to mammals. Further, because Drosophila do not possess classic estrogen receptors or estrogen, this research suggests that BPA can impact neurodevelopment by molecular mechanisms distinct from its role as an estrogen mimic.

Patients with myelodysplastic syndrome (MDS) frequently receive red blood cell (RBC) transfusions for anaemia resulting from ineffective erythropoiesis. While RBC transfusions may rapidly increase haemoglobin values, their impact on clinical and health services outcomes in MDS patients has not previously been summarized. We conducted a systematic review of the literature to evaluate risks and benefits of RBC transfusions in MDS patients. We searched electronic databases (MEDLINE, Embase, CENTRAL, CINAHL) from inception through June 4, 2021 to identify studies reporting data on RBC transfusions in MDS patients. Full text publications that assessed RBC transfusions as an intervention and reported at least one clinical, laboratory, or healthcare outcome associated with transfusion were included. Study characteristics, transfusion information and transfusion-related outcomes were extracted and reported. We identified 1243 original studies, of which 38 met eligibility requirements and were included. Fourteen reported on survival following diagnosis of MDS, with the majority reporting poorer survival among patients receiving or requiring more frequent transfusions. Nine reported on transfusion-related iron overload and its complications. Other outcomes included rates of allo/autoimmunization and adverse transfusion reactions, and healthcare costs incurred by patients with a greater transfusion burden. Only two studies reported on symptom relief following transfusion. This review underscores transfusion dependence as a negative prognostic factor for MDS patients and highlights the paucity of evidence surrounding quality of life and symptom-related outcomes following RBC transfusions in this population. Further study of patient-important outcomes associated with transfusion in MDS patients is warranted to improve therapeutic recommendations and inform resource allocation.

Objective The objective of this work was to carry out a meta-analysis of RCTs comparing intraoperative RBC transfusion strategies to determine their impact on postoperative morbidity, mortality, and blood product use. Summary of background data RBC transfusions are common in surgery and associated with widespread variability despite adjustment for casemix. Evidence-based recommendations guiding RBC transfusion in the operative setting are limited. Methods The search strategy was adapted from a previous Cochrane Review. Electronic databases were searched from January 2016 to February 2021. Included studies from the previous Cochrane Review were considered for eligibility from before 2016. RCTs comparing intraoperative transfusion strategies were considered for inclusion. Co-primary outcomes were 30-day mortality and morbidity. Secondary outcomes included intraoperative and perioperative RBC transfusion. Meta-analysis was carried out using random-effects models. Results Fourteen trials (8641 patients) were included. One cardiac surgery trial accounted for 56% of patients. There was no difference in 30-day mortality [relative risk (RR) 0.96, 95% confidence interval (CI) 0.71-1.29] and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53, 95% CI 0.43-0.64) and perioperative (RR 0.70, 95% CI 0.62-0.79) blood transfusions were significantly lower in the restrictive group compared to the liberal group. Conclusions Intraoperative restrictive transfusion strategies decreased perioperative transfusions without added postoperative morbidity and mortality in 12/14 trials. Two trials reported worse outcomes. Given trial design and generalizability limitations, uncertainty remains regarding the safety of broad application of restrictive transfusion triggers in the operating room. Trials specifically designed to address intraoperative transfusions are urgently needed.

BACKGROUND Adherence to antiretroviral (ARV) therapy is critical for achieving HIV RNA suppression in people living with HIV and for preventing HIV infection in uninfected individuals using preexposure prophylaxis. However, a high level of adherence can be challenging to achieve for people living with HIV on lifelong ARVs and for HIV-negative individuals using daily preexposure prophylaxis who are not at daily risk for HIV infection. Current biological measures of adherence are invasive and use bioanalytical methods that do not allow for real-time feedback during a clinic visit. This study was designed to test the feasibility and acceptability of using MedViewer, a novel, minimally invasive, hair-based assay that measures longitudinal ARV drug adherence in real time and provides an output for provider-patient discussion. OBJECTIVE The primary objectives were to investigate the feasibility of delivering the MedViewer results as planned, the acceptability of participation in a discussion of the MedViewer results, and the appropriateness of using MedViewer for adherence counseling. The secondary objectives were to investigate additional dimensions of feasibility, acceptability, and appropriateness of using the MedViewer test during a routine clinic visit for people with HIV. METHODS The proposed study was a single-arm cross-sectional study among patients receiving HIV care and providers of HIV care in a southeastern infectious disease clinic. The study originally planned to implement the MedViewer test with 50 eligible patients who were living with HIV across 2 viral load strata (undetectable or detectable plasma HIV RNA over the previous 2 years), administer brief visit-specific questionnaires to all patient and provider participants, and conduct qualitative in-depth interviews and quantitative end-line questionnaires with a subsample of patient participants (n=30) and all provider participants. RESULTS The Establishing Novel Antiretroviral Imaging for Hair to Elucidate Nonadherence study was funded by the National Institute of Allergy and Infectious Diseases and approved by the local institutional review board on November 4, 2019. Provider participant enrollment began on January 17, 2020, and patient participant enrollment began on January 22, 2020. Participant enrollment was halted on March 16, 2020, because of the COVID-19 pandemic (16 providers and 10 patients on study). Study activities resumed on February 2, 2021, with COVID-19 modifications approved by the local institutional review board. Participant enrollment closed on October 8, 2021, and data collection closed on November 15, 2021. In total, 36 unique patient participants, representing 37 samples, and 20 provider participants were enrolled. Data analysis and manuscript writing will take place throughout 2023. CONCLUSIONS We anticipate that the data collected through this study will provide important insights regarding the feasibility, acceptability, and appropriateness of incorporating new real-time longitudinal, minimally invasive adherence tests into routine clinical care and identify potential barriers to medication adherence among patients. CLINICALTRIAL ClinicalTrials.gov NCT04232540; https://clinicaltrials.gov/ct2/show/NCT04232540 INTERNATIONAL REGISTERED REPORT RR1-10.2196/41188

BACKGROUND Ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) has largely replaced conventional planar V/Q scan in nuclear medicine departments for pulmonary embolism (PE) diagnosis. However, the diagnostic performance of the test and its role in the diagnostic management of acute PE are still a matter of debate. OBJECTIVE The primary aim was to establish the diagnostic accuracy (sensitivity, specificity) of V/Q SPECT for PE diagnosis. The secondary aim was to review the clinical outcomes of patients investigated for PE suspicion with a standardized algorithm based on V/Q SPECT. METHODS We conducted a systematic review of diagnostic accuracy and management outcome studies involving patients evaluated with V/Q SPECT for suspected acute PE. We searched from inception to June 23, 2020, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for diagnostic accuracy studies, randomized controlled trials, and observational cohort studies. The methodological quality and risk of bias of eligible studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and the Risk of Bias in Nonrandomized Studies of Interventions tools. RESULTS We identified 13 accuracy studies and one prospective outcome study. Eleven diagnostic accuracy studies were deemed at high risk of bias in at least two of the four domains of QUADAS-2 evaluation and a further two studies raised concerns regarding the applicability of results, precluding the meta-analysis for accuracy indices. The only prospective cohort study demonstrated critical risk of bias. CONCLUSIONS Although V/Q SPECT has been widely implemented in daily clinical practice, the exact diagnostic performance of V/Q SPECT for PE is still unknown. This systematic review clearly identifies knowledge gaps and sets the agenda for future research.

Postoperative pancreatic fistula (POPF) is a major source of morbidity following pancreatic resection. Surgically placed drains under suction or gravity are routinely used to help mitigate the complications associated with POPF. Controversy exists as to whether one of these drain management strategies is superior. The objective was to identify and compare the incidence of POPF, adverse events, and resource utilization associated with passive gravity (PG) versus active suction (AS) drainage following pancreatic resection. MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched from inception to May 18, 2020. Outcomes of interest included POPF, post-pancreatectomy hemorrhage (PPH), surgical site infection (SSI), other major morbidity, and resource utilization. Descriptive qualitative and pooled quantitative meta-analyses were performed. One randomized control trial and five cohort studies involving 10 663 patients were included. Meta-analysis found no difference in the odds of developing POPF between AS and PG (p = 0.78). There were no differences in other endpoints including PPH (p = 0.58), SSI (wound p = 0.21, organ space p = 0.05), major morbidity (p = 0.71), or resource utilization (p = 0.72). The risk of POPF or other adverse outcomes is not impacted by drain management following pancreatic resection. Based on current evidence, a suggestion cannot be made to support the use of one drain over another at this time. There is a trend toward increased intra-abdominal wound infections with AS drains (p = 0.05) that merits further investigation.

Background and purpose Recovery after intracerebral haemorrhage (ICH) is often slower than ischemic stroke. Despite this, ICH research often quantifies recovery using the same outcome measures obtained at the same timepoints as ischemic stroke. The primary objective of this scoping review is to map the existing literature to determine when and how outcomes are being measured in prospective studies of recovery after ICH. Methods We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science from inception to November 2019, for prospective studies that included patients with ICH. Two investigators independently screened the studies and extracted data around timing and type of outcome assessment. Results Among the 9761 manuscripts reviewed, 395 met inclusion criteria, of which 276 were observational studies and 129 were interventional studies that enrolled 66274 patients. Mortality was assessed in 93% of studies. Functional outcomes were assessed in 85% of studies. The most frequently used functional assessment tool was the modified Rankin Scale (mRS) (60%), followed by the National Institute of Health Stroke Severity Scale (22%) and Barthel Index (21%). The most frequent timepoint at which mortality was assessed was 90 days (41%), followed by 180 days (18%) and 365 days (12%), with 2% beyond 1 year. The most frequent timepoint used for assessing mRS was 90 days (62%), followed by 180 days (21%) and 365 days (17%). Conclusion While most prospective ICH studies report mortality and functional outcomes only at 90 days, a significant proportion do so at 1 year and beyond. Our results support the feasibility of collecting long-term outcome data to optimally assess recovery in ICH.

IntroductionInsulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and meta-analysis intends to determine if available scientific knowledge supports an association between insulin resistance and post-stroke outcomes in patients without diabetes.Methods and analysisThe authors will conduct a literature search in Medline, Embase, Web of Science and Cochrane Central. The review will include studies that assess the association between elevated insulin homeostasis model of insulin resistance (HOMA-IR) and post-stroke outcome (functional outcome and recurrent stroke). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will be used. The primary outcome will be post-stroke functional outcome (Modified Rankin Scale), and the secondary outcome will be recurrent ischaemic stroke. Comparison of outcome will be made between highest and lowest HOMA-IR range (as defined in each article included in this systematic review). Risk of bias will be assessed qualitatively. Meta-analysis will be performed if sufficient homogeneity exists between studies. Heterogeneity of outcomes will be assessed by I².Ethics and disseminationNo human or animal subjects or samples were/will be used. The results will be published in a peer-reviewed journal, and will be disseminated at local and international neurology conferences.PROSPERO registration numberCRD42020173608.

The most suitable analytic method to systematically analyze numerous trials with contradictory results is unclear. Multiple trials assessing the use of N-acetylcysteine (NAC) for prevention of contrast-induced acute kidney injury (CI-AKI) have had contradictory results with recent trials confirming a lack of benefit.To systematically review the literature on NAC for the prevention of CI-AKI, and to explore the heterogeneity, publication bias, and small-study effect to determine the most suitable analytic method in a setting where the literature is contradictory.Medline, Embase, and Cochrane Central Register of Controlled Trials databases were used to find randomized clinical trials (RCTs) comparing NAC with any other prophylactic agent or placebo in adults.The search included studies published in English from database inception to January 2020. Two independent reviewers screened the studies, extracted data, and performed the risk of bias assessment.A meta-analysis was conducted about the effect of NAC on CI-AKI, the need for dialysis, and mortality. Fixed and random effects analyses were also performed. Funnel plots and the trim and fill method were used for assessment of publication bias. Metaregression was performed to explore the heterogeneity and subgroup analysis to examine the association between NAC and CI-AKI when studies were categorized according to sample size and number of events.A total of 101 trials were included in this meta-analysis. The median sample size was 112 (range, 20 to 4993). Twenty-nine trials had a sample size of 200 or more, and only 3 trials had a sample size of 500 or more. Forty-five trials reported the need for kidney replacement therapy, and 41 trials reported mortality as an outcome. NAC seemed to show a benefit, with a pooled OR of 0.72 (95% CI, 0.63-0.82) using random effects model and a pooled OR of 0.82 (95% CI 0.76-0.90) using a fixed effects model. However, there was significant heterogeneity (I2 = 37.6; P .001) and significant publication bias, which was reduced only when restricting to large RCTs (N ≥ 500). The clinical outcomes (ie, the need for kidney replacement therapy and mortality) revealed little heterogeneity and no publication bias, and each provided a robust neutral summary result.In this meta-analysis, NAC was associated with a benefit in the prevention of CI-AKI. However, because of substantial publication bias and other biases, standard meta-analytic techniques resulted in significant heterogeneity and a spurious, or factitious, association, even when using a random effects model. When the analysis was restricted to RCTs with a large sample size to account for publication bias or restricted to trials with clinical outcomes, this issue was reduced and resulted in more robust and neutral effect sizes.

OBJECTIVES The objective of this work was to carry out a systematic review of clinical practice guidelines (CPGs) pertaining to intraoperative red blood cell (RBC) transfusions, in terms of indications, decision-making, and supporting evidence base. SUMMARY OF BACKGROUND DATA RBC transfusions are common during surgery and there is evidence of wide variability in practice. METHODS Major electronic databases (MEDLINE, EMBASE, and CINAHL), guideline clearinghouses and Google Scholar were systematically searched from inception to January 2019 for CPGs pertaining to indications for intraoperative RBC transfusion. Eligible guidelines were retrieved and their quality assessed using AGREE II. Relevant recommendations were abstracted and synthesized to allow for a comparison between guidelines. RESULTS Ten guidelines published between 1992 and 2018 provided indications for intraoperative transfusions. No guideline addressed intraoperative transfusion decision-making as its primary focus. Six guidelines provided criteria for transfusion based on hemoglobin (range 6.0-10.0 g/dL) or hematocrit (

IntroductionCervical artery dissection, including carotid and vertebral artery dissection, is an important cause of stroke in the young. Risk of developing cervical artery dissection has been associated with physical activity in various forms and has been presumed to be related to minor trauma and mechanical stretching of the cervical arteries. This systematic review will aim to synthesise data on the risk of recurrent cervical artery dissection after an initial dissection. This information may be applied to further understand the natural history of this disease, and potentially to help direct evidence-based discussions on safe return to activity after dissection.Methods and analysisA broad search of multiple electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science) will be conducted to identify studies published as of 13 November 2019, examining all-comers with cervical artery dissection observed over time. Studies will be screened by two independent reviewers in a two-level process to determine eligibility for inclusion. Data will be pooled from eligible articles and the main outcome of recurrent cervical artery dissection at 5 years will be determined using quantitative analysis.Ethics and disseminationEthics approval is not necessary as no primary data are being collected. The information will be disseminated in the form of a systematic review article which will be submitted to a peer-reviewed medical journal.PROSPERO registration numberCRD42020166105.

BackgroundResistant hypertension is quite prevalent and a risk factor for cardiovascular events. Patients with suspected resistant hypertension undergo more screening intensity for secondary hypertension, despite some of them being non-adherent to prescribed pharmacotherapy. The prevalence of non-adherence in this setting varies from about 5 to 80% in the published literature. Apart from the wide range, the relation between method of assessment and prevalence is not well established. Our objective was to establish the overall prevalence of non-adherence in the apparent treatment resistant hypertension population, explore causes of heterogeneity, and evaluate the effect of the method of assessment on the estimate of non-adherence.MethodsWe performed a systematic review and meta-analysis. MEDLINE, EMBASE Classic+EMBASE, Cochrane, CINAHL, and Web of Science were searched for relevant articles. Details about the method of adherence assessment were extracted from each included article and grouped into direct and indirect. Pooled analysis was performed using the random effects model and heterogeneity was explored with metaregression and subgroup analyses.ResultsThe literature search yielded 1428 studies, of which 36 were included. The pooled prevalence of non-adherence was 35% (95% confidence interval 25 – 46 %). For indirect methods of adherence assessment, it was 25% (95% CI 15 – 39 %), whereas for direct methods of assessment, it was 44% (95% CI 32 – 57 %). Metaregression suggested gender, age, and time of publication as potential factors contributing to the heterogeneity.ConclusionsNon-adherence to pharmacotherapy is quite common in resistant hypertension, with the prevalence varying with the methods of assessment.Brief SummaryResistant hypertension is known to be a risk factor for cardiovascular events. These patients also undergo higher screening intensity for secondary hypertension. However, not all patients with apparent treatment resistant hypertension have true resistant hypertension, with some of them being non-adherent to prescribed pharmacotherapy. This systematic review aims to establish the overall prevalence of non-adherence in the apparent treatment resistant hypertension population and assess the relative contributions of non-adherence assessed with direct and indirect measures.

Anemia is a frequently diagnosed condition that may be a symptom of or complication of many illnesses affecting patients of all demographics. Anemia can lead to both worsened clinical outcomes and reduced quality of life. Patient-reported outcome measures (PROMs) are methodological tools used to capture the impact of disease on patient well-being. Use of PROMs in medical research is becoming more common as it is increasingly recognized that disease outcomes of interest to researchers and clinicians are not always consistent with patients' greatest concerns related to their diseases. We conducted a scoping review to characterize the studies that have evaluated patient-centered outcomes using PROMs in patients undergoing treatment for anemia. We conducted a search of Medline (Ovid), EMBASE (Ovid), PsychINFO, and CINAHL databases for studies published until January 2017 that investigated an intervention to treat anemia in any patient population and used at least 1 PROM to evaluate patient-centered outcomes. A descriptive synthesis was performed to characterize the PROMs used and to evaluate the quality of patient-centered outcome (PCO) reporting. Of the 3224 studies identified in the initial search, 130 met all eligibility criteria. We found that the population most frequently studied was oncology patients (46.2% of studies). The therapy for anemia evaluated in the most studies was erythropoietin-stimulating agents (77.7% of studies). The most commonly used PROM was the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy tool (46.9%), and the majority of studies used only 1 PROM tool (53.1%). We found significant variability in the quality of PCO reporting across all included studies. Improved methodologic rigor in the assessment of PCOs in anemia management is needed in future studies.

BACKGROUND The risks and benefits of red blood cell (RBC) transfusion in palliative care patients remain poorly understood. We reviewed the literature to summarize available information on RBC transfusion in this population. STUDY DESIGN AND METHODS We searched electronic databases (MEDLINE, Embase, PsycINFO, CINAHL) from inception through September 2016 to identify studies reporting data on palliative patients receiving RBC transfusion. Original studies that assessed RBC transfusion as an intervention and reported at least one clinical outcome were included. Study characteristics, results on transfusion-related outcomes, and authors' conclusions on the value of transfusion in palliative patients were abstracted and reported. RESULTS We identified 1839 studies, of which 137 were selected for data extraction and 13 were included (11 case series, one prospective cohort, and one retrospective cohort). Nine studies addressed symptom relief following transfusion using subjective symptom scales, of which eight (89%) indicated some degree of short-term benefit and one study (11%) showed no benefit. Posttransfusion survival was reported in four studies—one demonstrated prolonged survival in patients receiving RBC transfusion; three had no comparison group. Other outcomes reported included hemoglobin values posttransfusion in four studies and adverse events following transfusion in three studies. CONCLUSIONS In palliative care, RBC transfusion may provide symptom relief and improve subjective well-being, though the duration and magnitude of this effect, and transfusion-associated risks specific to this population remain unclear. Currently, no high quality evidence exists to support or guide the use of RBC transfusion in this population. Moreover, the clinical heterogeneity within the palliative population limits the interpretation of most studies.

Background: Anaemia is a nearly universal complication of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) have been demonstrated to improve clinical outcomes and quality of life (QOL) in renal patients with anaemia. Patient-reported outcome measures (PROMs) are increasingly being used to evaluate the patient-centred impact of medical therapy. Here, we describe a systematic review of studies that evaluated patient-centred outcomes (PCOs) in renal patients undergoing anaemia treatment. Methods: We conducted a search of Medline (Ovid), EMBASE (Ovid), PsychINFO, and CINAHL databases for studies published until March 2018 that investigated an intervention to treat anaemia in renal patients and used at least one PROM. We also performed a quality assessment for all included studies. Statistical analyses characterized each study, PROMs used, the quality of PCO reporting, and the association between haematological outcomes and PCOs. Results: Of the 3,533 studies identified in the database search, 21 met all eligibility criteria. Fourteen (67%) of the studies were randomized-controlled trials. Most studies (81%) investigated CKD patients, 14% investigated post-renal transplant patients and 5% assessed patients with heart disease on haemodialysis. The most common anaemia intervention, used in 95% of studies, was ESAs. Forty-three percent of studies utilized one PROM, most commonly the SF-36, a measure of QOL not specifically created for use in nephrology patients. About a third of studies selectively reported PROM subscales, rather than reporting all subscales. Notable biases among included studies included lack of blinding, selective outcome reporting, and lack of power estimates for PCOs. We did not find a statistically significant association between improvements in haemoglobin and QOL. Conclusions: Future studies employing anaemia and nephrology-specific PROMs and conducted with greater rigour, standardization in the research methods, and reporting of PCOs in renal populations will improve understanding of PCOs in this patient group and hopefully improve patient outcomes and experiences.

Background: It is important for medical practitioners to be aware of the effect of iodinated contrast media on the residual renal function (RRF) of dialysis patients who require diagnostic or therapeutic imaging procedures. Preservation of RRF is important given that it is a robust predictor of higher survival. However, the absence of any effect would allow for easier diagnostic or therapeutic imaging tests to be performed. Objective: This systematic review with meta-analysis will quantify the effect of intravascular administration of iodinated contrast on the residual function of adult dialysis patients. Study Design: The selection criteria included adult (age ≥ 18 years) populations undergoing dialysis, who have been administered an intravascular contrast. The primary outcome was the measurement of residual function. Secondary outcomes were disease progression from peritoneal dialysis to hemodialysis, hospitalization following contrast administration, and all-cause mortality. Results: Nine studies including 434 patients met the inclusion criteria. A meta-analysis was performed on 7 trials with complete quantitative data. The weighted difference in means was −0.16 mL/min (95% confidence interval −0.66 to 0.34 mL/min; p = 0.53), suggesting a small reduction in residual function following contrast administration. Significant heterogeneity in the data was observed, with a Cochran Q of 35.83 and an I2 of 83.25 (p < 0.0001). Subgroup analysis of retrospective versus prospective study design resolved heterogeneity. Few data were reported for clinical outcomes. Limitations: Small sample size of included studies. Conclusion: Intravascularly administered contrast media may not result in a significant reduction of residual function in dialysis patients.

IntroductionWomen have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care.ObjectiveIn an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them.MethodologyThis scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher’s Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics.SignificanceThe scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials.Ethics and disseminationResearch ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.

During the 2013-2015 Ebola virus disease (EVD) outbreak in West Africa, response efforts focused on containing the disease and reducing the number of new cases to zero. While this focus was important, protocols were never established to protect adolescent girls and young women during the outbreak. As quarantines and school closures were put in place to contain the spread of disease, women and adolescent girls were vulnerable to coercion, exploitation, and sexual abuse, some of which resulted in unwanted pregnancies. Young women and adolescent girls were also unable to attend community meetings where education and instructions were given about how to protect themselves from contracting the disease. While the number of Ebola-infected patients and deaths were recorded accurately, victims of violence during the outbreak went uncounted, unrecognized, and unattended. Gender was overlooked during the response, leaving young girls highly vulnerable. Future response must ensure equitable health systems and consider sexual and reproductive health services as essential during response. The creation of safe spaces and empowering teenage girls with information and support is important. Safe spaces can provide adolescent girls with security, livelihood skills, psychosocial counselling for gender-based violence, and access to sexual and reproductive health information and referral services.

N-acetylcysteine (NAC) is an antioxidant which can regenerate glutathione and is primarily used for acetaminophen overdose. It is also a potential therapy to prevent iatrogenic acute kidney injury or slow the progression of chronic kidney disease. It has been considered in this context by many studies with mixed results. Notably, a biological-mechanism rationale for a protective effect of NAC has never been adequately reported. Among conflicting reports, there appears to be evidence that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, a systematic review of the literature will be conducted to determine whether there is an effect of NAC on kidney function measured with serum creatinine.To determine the effect of NAC on kidney function.A systematic review and meta-analysis.Prospective studies, with administration of NAC, in the absence of any other change in kidney function (such as contrast administration or surgery).Adult humans aged 18 years old or more, either healthy volunteers or with chronic kidney disease, were administered with NAC. Populations having little to no kidney function such as in end-stage kidney disease will be excluded.Serum creatinine and/or cystatin C measurements before and after NAC administration.An information specialist will assist in searching MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify all study types including randomized controlled trials, and prospective cohort studies reporting change in serum creatinine after NAC administration. Two reviewers will independently screen the titles and abstracts of the studies obtained from the search using predefined inclusion criteria and will then extract data from the full texts of selected studies. The weighted mean difference will be calculated for change in creatinine with NAC, using random-effects analysis. Quality assessment will be done with the Cochrane Risk of Bias tool for randomized trials and the Newcastle-Ottawa Scale for observational studies.The outcome of interest is kidney function as reported by either change in serum creatinine and/or serum cystatin C measurement for randomized trials or comparing baseline (pre-NAC dose) values and those following the NAC dose.Possible heterogeneity and publication bias and lack of mechanistic data.This systematic review will provide a synthesis of current evidence on the effect of NAC on serum creatinine measurement. These findings will provide clinicians with guidelines and serve as a strong research base for future studies in this field.This review is registered with PROSPERO, CRD42017055984.La N-acétylcystéine (NAC) est un antioxydant capable de régénérer le glutathion et principalement utilisé pour traiter les cas de surdose d’acétaminophène. La NAC pourrait également s’avérer efficace comme traitement préventif de l’insuffisance rénale aiguë iatrogénique ou pour ralentir la progression de l’insuffisance rénale chronique. Cette substance a fait l’objet de plusieurs études dans ce contexte, mais les résultats demeurent mitigés. Notamment, il reste toujours à rapporter adéquatement une justification de l’effet protecteur de la NAC sur la base d’un mécanisme biologique. Parmi les rapports contradictoires, certaines données montreraient que la NAC abaisse artificiellement les valeurs de créatinine sérique mesurées sans améliorer la fonction rénale, potentiellement par interférence de l’essai. À la lumière de ces résultats divergents, une revue systématique de la littérature sera effectuée pour déterminer si la NAC produit un effet sur la fonction rénale mesurée par la créatinine sérique.Mesurer l’effet de l’administration de NAC sur la fonction rénale.Une revue systématique de la littérature et une méta-analyse.Les études prospectives avec administration de NAC sans autres changements dans la fonction rénale; l’administration d’un produit de contraste ou une intervention chirurgicale, par exemple.Des adultes, volontaires sains ou atteints de néphropathie chronique, ayant reçu de la NAC. Seront exclues les populations dont la fonction rénale est faible ou inexistante; notamment, les cas d’insuffisance rénale terminale.Des mesures de la créatinine sérique et/ou de la cystatine C faites avant et après l’administration de NAC.Un documentariste spécialisé assistera les recherches dans les bases de données MEDLINE, EMBASE et Cochrane CENTRAL afin de répertorier tous les types d’essais, y compris les essais contrôlés à répartition aléatoire, et toutes les études de cohorte prospectives faisant état d’une variation de la créatinine sérique à la suite de l’administration de NAC. À l’aide de critères d’inclusion prédéfinis, deux réviseurs seront indépendamment chargés de trier les titres et abrégés des études répertoriées lors de la revue de la littérature. Ils devront ensuite extraire les données des textes des études qui auront été retenues. Une analyse des effets aléatoires sera utilisée pour calculer la moyenne pondérée des écarts pour les variations observées dans les mesures de créatinine en présence de NAC. La qualité des essais aléatoires sera évaluée à l’aide de l’outil Cochrane sur le risque de biais, et celle des études observationnelles sera mesurée avec l’échelle de Newcastle-Ottawa.Le principal résultat d’intérêt est la fonction rénale telle que rapportée soit par un changement dans les mesures de créatinine sérique et/ou de la cystatine C dans les essais à répartition aléatoire, soit en comparant les valeurs mesurées avant et après l’administration d’une dose de NAC.L’hétérogénéité des données, de possibles biais de publication et un manque de données mécanistiques.Cette revue systématique offrira une synthèse des données probantes actuelles sur l’effet de la NAC sur les mesures de créatinine sérique. Ces résultats fourniront des lignes directrices aux cliniciens et serviront de bases solides pour les recherches futures dans ce domaine.

Background Development of fistula-in-ano following incision and drainage (I&D) of anorectal abscesses occurs in over 30% of patients. It is associated with significant patient morbidity and societal cost. The use of antibiotics following drainage is controversial, with randomized controlled trials reporting opposing conclusions regarding their influence on the rate of fistula formation. Given the significant burden associated with their development, it is imperative to determine strategies to minimize their occurrence. The objective of this review is to summarize the available evidence on the role of antibiotics following I&D of anorectal abscesses on fistula formation. Secondary objectives include determining if antibiotics are associated with morbidity, repeat presentation to the emergency department, and requirement for reoperation. Methods/design MEDLINE, EMBASE, CINAHL, Cochrane Central Registry of Controlled Trials, http://apps.who.int/trialsearch, and clinicaltrials.gov will be searched to identify published and ongoing unpublished interventional and observational studies evaluating the role of antibiotics post I&D on the incidence of fistula formation. There will be no restriction on language, date, or journal. Title and abstracts as well as full texts will be screened in duplicate based on inclusion and exclusion criteria. The Cochrane Risk of Bias tool and ROBINS-I will be used to assess risk of bias in randomized and non-randomized studies, respectively. Our primary outcome is the incidence of fistula formation; secondary outcomes include morbidity, representation to ED, and reoperation. Study heterogeneity will be calculated with Cochran’s Q test, P value, and I2 index. SASS (version 9.4) will be used for meta-analysis. Discussion This is the first study to review the available evidence on adjuvant antibiotics and incidence of fistula formation following I&D of anorectal abscesses. Systematic review registration PROSPERO CRD42018092044 Electronic supplementary material The online version of this article (10.1186/s13643-019-1002-z) contains supplementary material, which is available to authorized users.

INTRODUCTION Chest pain is the second leading cause for emergency department (ED) visits in the United States; however

Resistant hypertension, usually defined as blood pressure remaining above goal despite the concurrent use of 3 or more antihypertensive agents of different classes, is common (about 10% prevalence) and known to be a risk factor for cardiovascular events. These patients also undergo more screening intensity for secondary hypertension. However, not all patients with apparent treatment-resistant hypertension have true resistant hypertension, with some of them being nonadherent to prescribed pharmacotherapy. The prevalence of nonadherence varies from about 5% to 80% in the published literature. However, the relative contributions of intentional and nonintentional nonadherence are not well described. Nonintentional nonadherence refers to occasional forgetfulness and/or carelessness and can sometimes be related to an inability to follow instructions, because of either cognitive or physical limitations. Intentional nonadherence refers to an active process in which a patient may choose to alter the prescribed medication regimen by discontinuing medications, skipping doses, or modifying doses or dosing intervals.Our objective is to establish the overall prevalence of nonadherence in the apparent treatment-resistant hypertension population and evaluate the relative contributions of nonintentional and intentional nonadherence subtypes.We will conduct a systematic review and meta-analysis.We will include observational studies and randomized controlled trials where adherence to antihypertensive medications is measured using a test of adherence, either direct or indirect.We will include adult human participants aged 18 years or older with a diagnosis of resistant hypertension.Data extracted from individual studies will include title, first author, design, country, publication year, funding body, method of assessing adherence to antihypertensive medication, prevalence of medication nonadherence, definition of resistant hypertension, sample size, sex, mean age, and coexistent comorbidities.A librarian will search the databases Medline, EMBASE, Cochrane, CINAHL, and Web of Science for studies meeting criteria for inclusion. Two reviewers will independently screen the titles and abstracts retrieved and assess the methodological quality of eligible full-text articles using the Cochrane Risk of Bias tool for clinical trials and the Newcastle-Ottawa Scale for observational studies. Summary estimates of prevalence will be generated using pooled analysis using the random-effects method. Subgroup analyses, sensitivity analyses, and evaluation of publication bias will also be performed.The outcomes of interest are the pooled prevalence of nonadherence to antihypertensive medication in apparent treatment-resistant hypertension and the prevalence of nonadherence based on different methods of assessing nonadherence (indirect vs direct), which will allow us to estimate the relative proportion of unintentional and intentional nonadherence subtypes in the overall phenomenon of medication nonadherence.Possible limitations of this study include the finding of severe heterogeneity, the limitations of the literature search, publication bias, and the lack of granular data in the published studies for a study-level meta-analysis.This systematic review will provide a synthesis of current evidence on the prevalence of medication nonadherence in apparent treatment-resistant hypertension and on the relative contributions of nonintentional and intentional nonadherence subtypes. These findings will provide clinicians with a better understanding of the factors underlying treatment-resistant hypertension and will serve as a strong research base to guide future research on interventions to address medication nonadherence as well as the nonintentional and intentional subtypes.This protocol has been registered with PROSPERO. We will add registration details once available.On définit généralement l’hypertension réfractaire comme une valeur de pression artérielle qui demeure au-dessus de la valeur cible, et ce, malgré l’administration concomitante d’au moins trois agents antihypertenseurs de classes différentes. L’hypertension réfractaire est fréquente (prévalence d’environ 10 %) et constitue un facteur de risque d’événements cardiovasculaires. Les patients atteints d’hypertension réfractaire font également l’objet d’un dépistage plus intensif de l’hypertension secondaire. Cependant, tous les cas apparents d’hypertension résistante au traitement ne constituent pas nécessairement des cas d’hypertension réfractaire. Certains résultent plutôt d’une inobservance de la pharmacothérapie prescrite. La littérature rapporte une prévalence d’environ 5 à 80 % de l’inobservance du traitement, mais les contributions relatives de l’inobservance intentionnelle et non intentionnelle ne sont pas clairement établies. L’inobservance non intentionnelle fait référence aux oublis occasionnels ou à la négligence, qui peuvent être liés à l’incapacité de suivre des instructions en raison de limitations physiques ou cognitives. L’inobservance intentionnelle désigne quant à elle un processus actif où le patient choisit consciemment de modifier la posologie de sa médication, soit en interrompant le traitement, en sautant des doses ou en modifiant les doses ou les intervalles posologiques.Nous souhaitons mesurer la prévalence globale de l’inobservance au traitement parmi les cas apparents d’hypertension réfractaire et établir la contribution relative des sous-types intentionnel et non intentionnel d’inobservance.Nous procéderons à une revue systématique et à une méta-analyse de la documentation pertinente.L’étude inclura les études observationnelles et les essais contrôlés à répartition aléatoire traitant d’une mesure de l’observance du traitement antihypertenseur au moyen d’un test d’observance direct ou indirect.Seront inclus tous les patients adultes ayant reçu un diagnostic d’hypertension réfractaire.Les données suivantes seront extraites de chaque étude : le titre de l’article, le nom de l’auteur principal, la méthodologie et le lieu de l’étude, l’année de publication, l’organisme ayant financé les travaux, la méthode employée pour la mesure de l’observance, la prévalence de l’inobservance, la définition d’hypertension réfractaire, la taille de l’échantillon, ainsi que le sexe, l’âge moyen et les comorbidités des patients.Un bibliothécaire fera une présélection des études répondant aux critères d’inclusion dans les bases de données Medline, EMBASE, Cochrane, CINAHL et Web of Science. Les titres et résumés des articles retenus seront révisés de façon indépendante par deux examinateurs qui évalueront également la qualité méthodologique des articles complets à l’aide de l’outil Cochrane sur le risque de biais (essais cliniques) et de l’échelle de Newcastle-Ottawa (études observationnelles). Des estimations sommaires de la prévalence seront générées par l’analyse de l’ensemble des données par une méthode à effets aléatoires. Nous procéderons également à des analyses de sous-groupes, à des analyses de sensibilité, de même qu’à l’évaluation des biais de publication.Le principal résultat attendu est la combinaison de la prévalence de l’inobservance du traitement antihypertenseur dans les cas d’hypertension réfractaire apparente et de la prévalence de l’inobservance selon la méthode employée pour la mesurer (indirecte ou directe). Ce résultat nous permettra d’estimer la proportion des sous-types (inobservance intentionnelle et non intentionnelle) dans l’ensemble des cas répertoriés d’inobservance au traitement.Les résultats pourraient être limités par une importante hétérogénéité, des facteurs limitant la recherche documentaire, des biais de publication et le manque de données agrégées dans les études publiées pour procéder à une méta-analyse au niveau de l’étude.Cette revue systématique constituera une synthèse des données probantes sur la prévalence de l’inobservance au traitement dans les cas apparents d’hypertension réfractaire et sur les contributions relatives des sous-types intentionnel et non intentionnel d’inobservance. Ces résultats permettront aux cliniciens de mieux comprendre les facteurs sous-tendant l’hypertension réfractaire. Ils serviront également de base solide pour orienter les recherches futures sur des interventions visant à aborder l’inobservance au traitement médicamenteux et ses sous-types intentionnel et non intentionnel.

Introduction Single photon emission computed tomography ventilation/perfusion (SPECT V/Q) imaging has many proponents within the nuclear medicine community and has already largely replaced planar V/Q scintigraphy in daily practice for the diagnosis of pulmonary embolism (PE). However, the test is still described in clinical guidelines as an experimental test because of insufficient evidence. Methods and analysis We will conduct a systematic review and a meta-analysis of diagnostic accuracy and management outcome studies involving patients evaluated with V/Q SPECT for suspected acute PE. We will search from inception to 19 December 2017 MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for diagnostic accuracy studies, randomised controlled trials and observational cohort studies. Two reviewers will conduct all screening and data collection independently. The methodological quality and risk of bias of eligible studies will be carefully and rigorously assessed using the Quality Assessment of Diagnostic Accuracy Studies-2, the Cochrane Collaboration’s tool and the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools. The primary outcomes will be sensitivity, specificity and likelihood ratios of V/Q SPECT for the diagnosis of acute PE. The secondary outcomes will be the rate of venous thromboembolism during a 3-month follow-up period in patients left untreated after a negative diagnostic work-up based on SPECT V/Q. Ethics and dissemination This study of secondary data does not require ethics approval. It will be presented internationally and published in the peer-reviewed literature. PROSPERO registration number CRD42018084095.

The purpose of this study is to evaluate the rate of duplicate publication in radiology journals. The secondary objective is to evaluate the sensitivity of iThenticate.From January 1993 to December 2013, Déjà Vu (a database of highly similar citations) and PubMed were used to search for similar citations in 53 radiology journals. Citations were screened independently by two reviewers and verified by a third using predefined criteria to determine true cases of duplicate publication. The overall rate of duplicate publication was calculated; analysis of rate by journal, impact factor, and publication year was performed. The sensitivity of iThenticate was evaluated by analyzing all identified duplicate publications.From 128,818 citations in the included journals, 1786 (Déjà Vu) and 104 (PubMed) were flagged as potential duplicates. Of these, 248 (226 from Déjà Vu and 22 from PubMed) were classified as true duplicate publications after application of our criteria. The overall rate was 1.92/1000 citations; it varied widely across journals from zero to over 10/1000 citations, showed no correlation with impact factor (R(2) = 0.06; p = 0.093), and no change over time (R(2) = 0.28; p = 0.515). iThenticate flagged 153 of 248 (61.9%) duplicates as "possible duplicates" (defined as overall percentage match30%) and identified the corresponding duplicate citation pair in 140 of 248 (56.7%) cases; in 98 of these, the duplicate citation pair was the highest percentage similarity match.Duplicate publications in radiology journals are uncommon. The rate varies widely between journals, but was not associated with journal impact factor and did not change over time. iThenticate shows promise for identification of duplicate publications; however, refinements may be necessary to maximize its effectiveness.