Viruses in chronic rhinosinusitis: a systematic review.

Background: Unlike acute rhinosinusitis (ARS) which is mostly viral in etiology, the role of viruses in chronic rhinosinusitis (CRS) remains unclear. Viruses may play a role in initiation, exacerbations or perpetuate chronic inflammatory responses in the sinonasal mucosa. Research needs to characterize whether viruses are part of the normal sinonasal microbiome, colonizers or pathogenic. Methods: Systematic review of the English literature was conducted. Following databases were searched with an initial search conducted in November 2021 and then updated through June 2023: Ovid Medline (1946 to present), Ovid Embase (1988 to present), Scopus (2004 to present) and Web of Science (1975 to present). MeSH (Medical Subject Headings) terms included: viruses, virus diseases, sinusitis, and rhinovirus. Keywords: virus, viral infection*, sinusitis, rhinovirus, chronic rhinosinusitis, CRS, respiratory virus, respiratory infection*, and exacerbat*. A supplementary search was conducted through September 2023: Ovid Medline (1946 to present), Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Daily. Keywords used were: virus, viral infection*, sinusitis, chronic rhinosinusitis, CRS, respiratory virus, respiratory infection*, and exacerbat*. Results: Thirty studies on viruses in CRS met inclusion criteria for full review. These included 17 studies on prevalence of virus in CRS, 5 examining probable causes of host susceptibility to viral infections in CRS, and 8 studies examining pathological pathways in viral association of CRS. The prevalence of viruses in nasal specimens of CRS subjects was higher as compared to controls in most studies, though a few studies showed otherwise. Rhinovirus was the most common virus detected. Studies showed that viruses may be associated with persistent hyper-responsiveness in the sinonasal mucosa, susceptibility to bacterial infections, upregulation of genes involved in the immune response and airway remodeling as well as CRS exacerbations. Presence of viruses was also associated with worse symptom severity scores in CRS subjects. Conclusion: Most data show higher presence of viruses in nasal and serum samples of CRS subjects as compared to controls but their exact role in CRS pathophysiology in unclear. Large studies with longitudinal sampling at all disease phases (i.e., prior to disease initiation, during disease initiation, during disease persistence, and during exacerbations) using standardized sampling techniques are needed to definitively elucidate the role of virus in CRS.

Does Initiation of Prophylactic Antiseizure Medication Improve Neurological Outcomes in Patients With Acute Intracerebral Hemorrhage?: A Critically Appraised Topic.

OBJECTIVE: The objective of this study was to critically assess current evidence regarding the role of prophylactic antiseizure medication in patients presenting with acute intracerebral hemorrhage (ICH). METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included resident neurologists, a medical librarian, and content experts in the fields of epilepsy, stroke neurology, neurohospitalist medicine, and neurocritical care. RESULTS: A randomized clinical trial was selected for critical appraisal. The trial assessed whether prophylactic levetiracetam (LEV) use reduced the risk of acute seizures in patients with ICH, as defined by clinical or electrographic seizure, captured by continuous electroencephalogram 72 hours after enrollment. A total of 42 patients were included in the final analysis (19 in the LEV group and 23 in the placebo group). There was a significantly higher occurrence of seizures in the placebo versus LEV group (LEV 16% vs placebo 43%, P = 0.043). There were no differences in functional outcomes between the groups at 3, 6, or 12 months (P > 0.1). CONCLUSIONS: The role of prophylactic treatment with antiseizure medication in ICH remains unclear.

Meteorological and environmental factors that impact pollen counts, allergenicity, and thresholds: A scoping review.

Background: Pollen is a key source of aeroallergens responsible for allergic rhinitis, conjunctivitis, and asthma. Objective: The goal of this scoping review was to summarize current available literature on the factors that affect pollen counts, allergenicity, and thresholds that induce symptoms in individuals who were sensitized. Methods: Several databases showed no published articles with a similar scope as of January 2022. A search of these data bases yielded 373 articles for assessment. These were then reviewed for relevance, and articles were selected to demonstrate the breadth of available data on pollen counts, allergenicity, and thresholds that induce symptoms in individuals who were sensitized. Additional articles were identified through examination of bibliographies of search-identified articles. Results: Several environmental factors have shown a correlation with pollen counts and allergen load, including the distance from the source, wind characteristics, pollen size, terrain, urban environments, air composition (particulate matter, CO2 levels, ozone, NO2), and weather conditions (humidity, thunderstorms, precipitation). Pollen thresholds at which symptoms were induced varied by study, pollen type, symptom, disease, and location. In addition, there was heterogeneity in study designs, threshold definition, and outcome measures. Conclusion: This scoping review demonstrates the plethora of variables that influence the relationship between pollen and the symptoms of allergic diseases. Analysis of the available data sheds light on the complex interaction between environmental and biologic factors that affect pollen's role in allergic diseases and provides guidance on multiple areas for further investigation.

Listening to Learners to Prepare for the Future: A Mayo Clinic College of Medicine and Science Benchmarking Survey.

In 2022, a benchmarking survey was completed to gage learner satisfaction with library services, spaces, and resources across 10 Mayo Clinic Libraries. The discussion for this project began around a previously published survey of what medical students wanted from their library. Librarians were asked if Mayo Clinic Libraries could do a similar survey, as a full survey of the Mayo Clinic College of Medicine and Science had not been done. Overall, the findings were positive and provide a baseline for future surveys.

Is Intravenous Immunoglobulin Effective in Reducing the Risk of Mortality and Morbidity in Neuroinvasive West Nile Virus Infection?: A Critically Appraised Topic.

BACKGROUND: The clinical benefit of intravenous immunoglobulin (IVIG) in adult individuals with neuroinvasive West Nile virus (niWNV) infection is not well substantiated. We sought to critically assess current evidence regarding the efficacy of IVIG in treating patients with niWNV. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-infectious diseases. RESULTS: The appraised study enrolled 62 participants with suspected niWNV, randomized into 3 different arms [37 participants in the Omr-IgG-am group, 12 in the Polygam group, and 13 in the normal saline (NS) group]. Omr-IgG-am and Polygam are different formulations of IVIG. IVIG safety, measured as rates of serious adverse events, was the primary study outcome while IVIG efficacy, measured as rates of unfavorable outcomes, was a secondary endpoint. The estimated rates of SAE were statistically similar in all groups (51.4% Omr-IgG-am, 58.3% Polygam, and 23.1% NS groups). Unfavorable outcomes also occurred at a similar rate between all the groups (51.5% Omr-IgG-am, 54.5% Polygam, and 27.3% NS). CONCLUSIONS: The appraised trial showed that Omr-IgG-am and Polygam are as safe as NS. Data on efficacy from this trial were limited by a small sample size. Phase III clinical trials on IVIG efficacy in NiWNV infection are needed.

Outcomes of Lymphovenous Anastomosis for Lower Extremity Lymphedema: A Systematic Review.

Lymphovenous anastomosis (LVA) is a microsurgical treatment for lymphedema of the lower extremity (LEL). This study systematically reviews the most recent data on outcomes of various LVA techniques for LEL in diverse patients. Methods: A comprehensive literature search was conducted in the Ovid MEDLINE, Ovid EMBASE, and Scopus databases to extract articles published through June 2021. Studies reporting data on objective postoperative improvement in lymphedema and/or subjective improvement in quality of life for patients with LEL were included. Extracted data comprised demographics, number of patients and lower limbs, duration of symptoms before LVA, surgical technique, duration of follow-up, and objective and subjective outcomes. Results: A total of 303 articles were identified and evaluated, of which 74 were ultimately deemed eligible for inclusion in this study, representing 6260 patients and 2554 lower limbs. The average patient age ranged from 22.6 to 76.14 years. The duration of lymphedema before LVA ranged from 12 months to 11.4 years. Objective rates of improvement in lymphedema ranged from 23.3% to 100%, with the greatest degree of improvement seen in patients with early-stage LEL. Conclusions: LVA is a safe and effective technique for the treatment of LEL of all stages. Several emerging techniques and variations may lead to improved patient outcomes.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). CONCLUSIONS: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Use of the Electronic Health Record During Clinical Encounters: An Experience Survey.

PURPOSE: Use of the electronic health record (EHR) during face-to-face clinical encounters affects communication, and prior research has been inconclusive regarding its effect. This survey study assessed health care practitioner use of EHR-specific communication skills and patient and practitioner experiences and attitudes regarding EHR use during clinical encounters. METHODS: For this US-based study, we distributed previously validated surveys to practitioners and adult patients (aged >18 years) at academic primary care practices from July 1, 2018 through August 31, 2018. The electronic practitioner survey was completed first; a paper survey was administered to patients after appointments. Descriptive statistics were calculated, and the Cochran-Armitage test was used to assess for associations between key variables. RESULTS: The practitioner response was 72.9% (43/59); patient response, 45.2% (452/1,000). Practitioners reported maintaining less eye contact (79.1%), listening less carefully (53.5%), focusing less on patients (65.1%), and visits feeling less personal (62.8%). However, patients reported that practitioners provided sufficient eye contact (96.8%) and listened carefully (97.0%); they disagreed that practitioners focused less on them (86.7%) or that visits felt less personal (87.2%). Patients thought EHR use was positive (91.7%); only one-third of practitioners (37.2%) thought that patients would agree with that statement. Practitioners reported stress, burnout, and a lack of sufficient time for EHR documentation. CONCLUSIONS: A discrepancy existed in this study between patient and practitioner experiences and attitudes about EHR use, which appeared to negatively affect the experience of health care practitioners but not patients. Organizations should adopt formal strategies to improve practitioner experiences with EHR use.

In Patients With Melanoma Brain Metastases, Is Combination Immune Checkpoint Inhibition a Safe and Effective First-Line Treatment? A Critically Appraised Topic.

BACKGROUND: Combined PD-1/PD-L1 and CTLA-4 immune checkpoint inhibition for the has been shown to produce superior results in the treatment of malignant melanoma when compared to monotherapy. However, patients with intracranial disease were excluded from these studies given their poor prognosis. OBJECTIVE: The objective of this study was to critically assess current evidence supporting the co-administration of PD-1/PD-L1 and CTLA-4 inhibitors in the treatment of melanoma brain metastases. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-oncology. RESULTS: A recent, open-label, non-comparative randomized phase II trial was selected for critical appraisal. This trial evaluated the efficacy and safety of nivolumab alone or in combination with ipilimumab in 79 adult patients with untreated, asymptomatic melanoma brain metastases. The rates of the primary outcome (intracranial response at ≥12 wk) in the primary endpoint cohort were 46% for cohort A (combination therapy) and 20% for cohort B (nivolumab monotherapy). No treatment related deaths were observed in the study. Grade 4 adverse events occurred in 9% of patients in cohort A and none in cohort B. CONCLUSIONS: Co-administration of ipilimumab and nivolumab as first-line therapy is effective in the treatment of asymptomatic melanoma brain metastases, with an acceptable safety profile.

Multicancer Early detection Panels (MCEDs) in the Primary Care Setting.

Multicancer early detection panels have recently become available to patients with a provider's prescription and an out-of-pocket fee. Beyond theoretical modeling, little is known about how these assays will impact primary care practices despite a high likelihood that primary care providers (PCPs) will be ordering these tests with some frequency. In particular, there are concerns about patient counseling, costs, frequency of testing, patient anxiety, and subsequent testing for a positive result. This review aims to appraise the current literature and provide a framework that PCPs can use to discuss these tests with patients and streamline their ordering, interpretation, and overall use into everyday practice.

A Scoping Review of Published Intimate Partner Violence Curricula for Medical Trainees.

Intimate partner violence (IPV) affects many, and health care has the potential to provide a safe space for individuals experiencing IPV. However, physicians cite lack of time and education as barriers. The aim of this study is to complete a review of published IPV curricula in medical school, residency training, and postresidency training. We performed a scoping review to provide a quantitative assessment and summary review of existing IPV curricula. In May 2020, a librarian conducted a search of Ovid MEDLINE, Ovid EMBASE, and Scopus. We evaluated each article for the following curriculum content and structure items: (1) year introduced; (2) delivery method; (3) curriculum type; (4) curriculum content; (5) curriculum effectiveness; and (6) implementation barriers. Fifty-six articles met criteria, most were for medical school learners (n = 32, 57.1%) and short-term (lasting less than one academic year) (n = 41, 73.2%). For residency, IPV curricula were most frequently taught in family medicine, internal medicine, and emergency medicine. Formal lecture and use of standardized patients were the most popular delivery methods. Most curricula taught risk factors for and identification of individuals who have experienced IPV. The most cited implementation barrier was limited time in standard medical education, followed by inability to measure the effectiveness of the curriculum. There was great variation in the methods of assessing effectiveness of IPV curricula. Published IPV curricula are varied, without consistent validated tools for assessing efficacy. Future initiatives to establish a standard of competency for medical students regarding IPV, including a standard curriculum, may better ensure that physicians are capable of identifying and caring for individuals who have experienced IPV.

In Patients With Functional Movement Disorders, Is Specialized Physical Therapy Effective in Improving Motor Symptoms?: A Critically Appraised Topic.

BACKGROUND: Functional movement disorders (FMD, aka psychogenic movement disorders) are very common and frequently chronic and disabling. Despite this, there is a paucity of evidence-based treatment to manage and alleviate these conditions. Specialized physical therapy (PT), involving sequential motor relearning and redirecting attention, has shown promise as a therapeutic intervention for motor symptoms. METHODS: The objective of this study was to critically assess current evidence regarding specialized PT compared with usual care in improving motor symptoms among patients with FMD. This was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of physical medicine and rehabilitation, physical and occupational therapy, psychiatry, and psychology. RESULTS: A randomized controlled feasibility trial was identified and selected for critical appraisal. This study randomized 60 patients with FMD to a 5-day specialized outpatient PT program or to general outpatient PT referral, and measured patient-reported and clinician-measured outcomes. At 6 months, 72% of patients in the intervention group had a good outcome compared with 18% of control group patients. Patients in the specialized outpatient PT program had significantly better outcomes in 3 Short-Form 36 (SF36) domains (d=0.46 to 0.79) and multiple other scales of physical and social function as well as clinician-measured outcomes. The intervention resulted in 0.08 additional quality-adjusted life years in a cost-effective manner. CONCLUSIONS: Current evidence suggests that in patients with FMD, specialized PT improves motor symptoms in a clinically significant, sustained, and cost-effective manner. This promising intervention warrants further investigation and replication.

Intra-articular therapy with methotrexate or tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic review.

BACKGROUND: Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections. METHODS: A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality. RESULTS: Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies. CONCLUSION: For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.

Is Autologous Stem Cell Transplantation a Safe and Effective Alternative to Whole Brain Radiation as Consolidation Therapy in Patients With Primary Central Nervous System Lymphoma?: A Critically Appraised Topic.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) is a promising alternative to whole brain radiation therapy (WBRT) in the treatment of primary central nervous system lymphoma (PCNSL). The objective of this study was to critically assess current evidence supporting the use of HD-ASCT as first-line consolidative therapy in PCNSL. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-oncology. RESULTS: A recent, open-label, noncomparative randomized phase II trial was selected for critical appraisal. This trial evaluated the efficacy and toxicity of consolidative therapy with HD-ASCT and WBRT in PCNSL in 2 separate treatment arms. A total of 140 patients with newly diagnosed PCNSL between the ages of 18 and 60 years were included. The primary endpoint of 2-year progression-free survival was met in 63% of patients in the WBRT arm and 87% in the HD-ASCT arm. Notably, an overall improvement in neurocognitive scores was observed following HD-ASCT, while WBRT was associated with worsened cognitive outcomes. CONCLUSIONS: In young patients with newly diagnosed PCNSL, consolidative therapy with HD-ASCT appears to be associated with less neurocognitive toxicity and may be more effective than WBRT at preventing relapses, however, at the cost of a higher treatment-related mortality.

Does the Initiation of Fluoxetine Postacute Stroke Result in Improved Functional Recovery?: A Critically Appraised Topic.

BACKGROUND: Stroke is a leading cause of disability worldwide. Selective serotonin reuptake inhibitors are often prescribed following stroke due to high rates of depression. Interest in selective serotonin reuptake inhibitor use for poststroke motor and functional recovery was generated after the publication of the Fluoxetine for motor recovery after acute ischemic stroke (FLAME) trial in 2011, which showed improved motor recovery in ischemic stroke patients with moderate to severe motor deficits. The objective of this study was to critically assess current evidence regarding the use of fluoxetine compared with placebo for poststroke functional recovery. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario and question, literature search, critical appraisal, results, evidence summary, commentary, and clinical bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, clinical epidemiologists, and content experts in the field of cerebrovascular neurology and physical medicine and rehabilitation. RESULTS: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the functional outcomes of subjects poststroke receiving fluoxetine versus placebo. There was no significant difference in functional outcome measured by the Modified Rankin Scale between the 2 groups. Prespecified secondary analysis showed significantly decreased rates of depression in the fluoxetine group, but significantly increased rates of bone fracture. CONCLUSION: Among patients with stroke, early initiation of fluoxetine did not result in improved functional recovery. Lower rates of depression were observed in the fluoxetine-treated group; however these patients experienced higher rates of bone fracture.

Does General Anesthesia Compared With Conscious Sedation Result in Better Outcomes in Acute Stroke Patients Undergoing Endovascular Therapy?

BACKGROUND: There is considerable controversy surrounding the optimal use of sedation in patients with acute ischemic stroke undergoing mechanical thrombectomy. Several retrospective studies have favored conscious sedation (CS) over general anesthesia (GA) in terms of functional outcomes and mortality. Recent data from randomized controlled trials has challenged this view. OBJECTIVE: The aim was to critically assess current evidence regarding the use of CS versus GA in mechanical thrombectomy for acute ischemic stroke. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology, vascular neurosurgery, and interventional neuroradiology. RESULTS: A randomized controlled trial was selected for critical appraisal. This trial compared 128 patients with acute ischemic stroke and large vessel occlusion from a single center (Aarhus University Hospital, Denmark), 65 of whom received GA and 63 received CS. No significant difference was detected for the primary outcome of volume of infarct growth. The rate of successful thrombectomy and favorable clinical outcomes for the GA arm was significantly higher in the intention-to-treat analysis. CONCLUSIONS: GA does not result in worse tissue outcomes or worse clinical outcomes when compared with CS in acute stroke patients with large vessel occlusion undergoing mechanical thrombectomy.

Trigeminal nerve electrophysiological findings in hemifacial atrophy: A systematic literature review and retrospective chart review.

OBJECTIVE: Hemifacial atrophy (HFA) is a rare disorder characterized by progressive unilateral wasting facial soft tissue, muscle, and/or bone. Trigeminal nerve abnormalities may contribute to or result from disease pathophysiology. We aimed to gain further insights into the role of trigeminal pathophysiology along the HFA severity spectrum. METHODS: A systematic literature review was performed according to PRISMA standards. Retrospective cases of HFA from the literature and Mayo Clinic EMG database were pooled for descriptive and semi-quantitative analysis. RESULTS: Overall, 13 total HFA patients were identified through literature and database reviews. Trigeminal nerve testing was abnormal in 9/13 (69%), exclusively in moderate-severe cases. Abnormalities suggested a peripheral (7/9, 78%) or mixed central/peripheral (2/9, 22%) localization. Trigeminal nerve abnormalities were not identified in any of the 4 cases with mild disease severity. CONCLUSION: Moderate to severe cases of HFA were associated with electrophysiological trigeminal abnormalities. No abnormalities were seen in mild cases of HFA. SIGNIFICANCE: Trigeminal nerve electrophysiology may serve as a biomarker of moderate-severe disease progression, likely reflecting the consequences of progressive soft tissue atrophy.

Clinical implications of synovial fluid specimen handling for crystal associated arthritides: A systematic review.

AIM: To identify the appropriate methods of synovial fluid (SF) specimen storage, manipulation and handling for crystal associated arthritides (CAA) diagnosis. METHOD: A systematic literature review was conducted using 5 medical databases to identify diagnostic studies assessing SF specimen handling for calcium pyrophosphate (CPP) and monosodium urate (MSU) crystals identification. All included studies were rated for quality using the Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: Fifteen studies, including 2 non-English language manuscripts, were included. Eight studies examined both types of crystals, while 3 studies examined CPP and 4 studies examined MSU crystals only. Overall, MSU crystals were more stable over time compared to CPP crystals. MSU stability was generally independent of time, preservative and temperature. CPP crystals deteriorated with time and were more stable if refrigerated. Ethylenediaminetetraacetic acid (EDTA) was a suitable preservative. Re-examining an initially negative SF sample at 24 hours facilitated detection of additional cases. Very few studies had an overall low risk of bias and applicability. CONCLUSION: Monosodium urate crystals remain stable over time independent of storage time, temperature and preservative. CPP crystals are mostly stable for 24-48 hours but can deteriorate with time. Overall, SF crystal examination should ideally be done within 24-48 hours. They may be stored at room temperature without any preservative. Otherwise, refrigeration (4°C/39°F) and EDTA preservation is reasonable. Stored SF re-examination, at 24 hours, helps identify a small number of additional MSU and CPP cases. Centrifugation techniques allow better and easier crystal identification, particularly CPP. Most studies were of unclear or low quality.

Intranasal Corticosteroid Therapy: Systematic Review and Meta-analysis of Reported Safety and Adverse Effects in Children.

OBJECTIVES: To address concerns related to the safety profile of both Food and Drug Administration (FDA)-approved and non-FDA-approved intranasal corticosteroid (INCS) use in the pediatric population. DATA SOURCE: Systematic review of MEDLINE, PubMed, and EMBASE databases using comprehensive search strategy, including all INCS formulations and adverse events. The study design was developed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Additional sources were identified from study references of relevant articles. REVIEW METHODS: A structured literature search was conducted. Extracted data included age, population size, study design, drug (dosage, route, and frequency), presence of hypothalamic-pituitary-adrenal (HPA) axis suppression, ocular symptoms, and growth velocity adverse events. RESULTS: A total of 33 studies met inclusion criteria. The studies included use of INCS as nasal sprays and drops. There were no persistent abnormalities noted in cortisol level or intraocular pressure change. Growth velocity reduction was reported in 3 of 10 randomized trials. Meta-analysis of epistaxis and headache showed no significant difference in the incidence of headache or epistaxis when FDA-approved INCSs were compared to placebo, with a relative risk of 1.12 (95% CI, 0.77-1.63; P = .56) and 0.84 (95% CI, 0.60-1.18; P = .32), respectively. Meta-analysis was not performed for growth velocity, HPA axis suppression, and ocular change. CONCLUSIONS: INCSs in FDA-approved routes of administration are generally safe to use in the pediatric population. Use of non-FDA-approved INCS drops may increase risk of iatrogenic Cushing's syndrome. Growth velocity reduction, HPA axis suppression, and visual changes due to INCS are uncommon.