Virtual urgent care is here to stay: driving toward safe, equitable, and sustainable integration within emergency medicine.

BACKGROUND: Virtual care in Canada rapidly expanded during the COVID-19 pandemic in a low-rules environment in response to pressing needs for ongoing access to care amid public health restrictions. Emergency medicine specialists now face the challenge of advising on which virtual urgent care services ought to remain as part of comprehensive emergency care. Consideration must be given to safe, quality, and appropriate care as well as issues of equitable access, public demand, and sustainability (financial and otherwise). The aim of this project was to summarize current literature and expert opinion and formulate recommendations on the path forward for virtual care in emergency medicine. METHODS: We formed a working group of emergency medicine physicians from across Canada working in a variety of practice settings. The virtual care working group conducted a scoping review of the literature and met monthly to discuss themes and develop recommendations. The final recommendations were circulated to stakeholders for input and subsequently presented at the 2023 Canadian Association of Emergency Physicians (CAEP) Academic Symposium for discussion, feedback, and refinement. RESULTS: The working group developed and reached unanimity on nine recommendations addressing the themes of system design, equity and accessibility, quality and patient safety, education and curriculum, financial models, and sustainability of virtual urgent care services in Canada. CONCLUSION: Virtual urgent care has become an established service in the Canadian health care system. Emergency medicine specialists are uniquely suited to provide leadership and guidance on the optimal delivery of these services to enhance and complement emergency care in Canada.

RéSUMé: CONTEXTE: Les soins virtuels au Canada ont rapidement pris de l'ampleur pendant la pandémie de COVID-19 dans un environnement où les règles sont peu strictes, en réponse aux besoins urgents d'accès continu aux soins dans un contexte de restrictions en santé publique. Les spécialistes de la médecine d'urgence sont maintenant confrontés au défi de conseiller sur les services de soins d'urgence virtuels qui devraient rester dans le cadre des soins d'urgence complets. Il faut tenir compte des soins sécuritaires, de qualité et appropriés, ainsi que des questions d'accès équitable, de la demande publique et de la durabilité (financière et autre). L'objectif de ce projet était de résumer la littérature actuelle et l'opinion d'experts et de formuler des recommandations sur la voie à suivre pour les soins virtuels en médecine d'urgence. MéTHODES: Nous avons formé un groupe de travail composé de médecins urgentistes de partout au Canada qui travaillent dans divers milieux de pratique. Le groupe de travail sur les soins virtuels a effectué un examen de la portée de la documentation et s'est réuni chaque mois pour discuter des thèmes et formuler des recommandations. Les recommandations finales ont été distribuées aux intervenants pour obtenir leurs commentaires, puis présentées au symposium universitaire 2023 de l'Association canadienne des médecins d'urgence (ACMU) pour discussion, rétroaction et perfectionnement. RéSULTATS: Le groupe de travail a élaboré et atteint l'unanimité sur neuf recommandations portant sur les thèmes de la conception du système, de l'équité et de l'accessibilité, de la qualité et de la sécurité des patients, de l'éducation et des programmes, des modèles financiers et de la viabilité des services virtuels de soins d'urgence au Canada. CONCLUSION : Les soins d'urgence virtuels sont devenus un service établi dans le système de santé canadien. Les spécialistes en médecine d'urgence sont particulièrement bien placés pour fournir un leadership et des conseils sur la prestation optimale de ces services afin d'améliorer et de compléter les soins d'urgence au Canada.

Gender equity of authorship in pulmonary medicine over the past decade.

BACKGROUND: Gender disparity in authorship broadly persists in medical literature, little is known about female authorship within pulmonary medicine. METHODS: A bibliometric analysis of publications from 2012 to 2021 in 12 journals with the highest impact in pulmonary medicine was conducted. Only original research and review articles were included. Names of the first and last authors were extracted and their genders were identified using the Gender-API web. Female authorship was described by overall distribution and distribution by country/region/continent and journal. We compared the article citations by gender combinations, evaluated the trend in female authorship, and forecasted when parity for first and last authorship would be reached. We also conducted a systematic review of female authorship in clinical medicine. RESULTS: 14,875 articles were included, and the overall percentage of female first authors was higher than last authors (37.0% vs 22.2%, p<0.001). Asia had the lowest percentage of female first (27.6%) and last (15.2%) authors. The percentages of female first and last authors increased slightly over time, except for a rapid increase in the COVID-19 pandemic periods. Parity was predicted in 2046 for the first authors and 2059 for the last authors. Articles with male authors were cited more than articles with female authors. However, male-male collaborations significantly decreased, whereas female-female collaborations significantly increased. CONCLUSIONS: Despite the slow improvement in female authorship over the past decade, there is still a substantial gender disparity in female first and last authorship in high-impact medical journals in pulmonary medicine.

Non-communicable diseases among adolescents: current status, determinants, interventions and policies.

BACKGROUND: Addressing non-communicable disease (NCDs) is a global priority in the Sustainable Development Goals, especially for adolescents. However, existing literature on NCD burden, risk factors and determinants, and effective interventions and policies for targeting these diseases in adolescents, is limited. This study develops an evidence-based conceptual framework, and highlights pathways between risk factors and interventions to NCD development during adolescence (ages 10-19 years) and continuing into adulthood. Additionally, the epidemiologic profile of key NCD risk factors and outcomes among adolescents and preventative NCD policies/laws/legislations are examined, and a multivariable analysis is conducted to explore the determinants of NCDs among adolescents and adults. METHODS: We reviewed literature to develop an adolescent-specific conceptual framework for NCDs. Global data repositories were searched from Jan-July 2018 for data on NCD-related risk factors, outcomes, and policy data for 194 countries from 1990 to 2016. Disability-Adjusted Life Years were used to assess disease burden. A hierarchical modeling approach and ordinary least squares regression was used to explore the basic and underlying causes of NCD burden. RESULTS: Mental health disorders are the most common NCDs found in adolescents. Adverse behaviours and lifestyle factors, specifically smoking, alcohol and drug use, poor diet and metabolic syndrome, are key risk factors for NCD development in adolescence. Across countries, laws and policies for preventing NCD-related risk factors exist, however those targeting contraceptive use, drug harm reduction, mental health and nutrition are generally limited. Many effective interventions for NCD prevention exist but must be implemented at scale through multisectoral action utilizing diverse delivery mechanisms. Multivariable analyses showed that structural/macro, community and household factors have significant associations with NCD burden among adolescents and adults. CONCLUSIONS: Multi-sectoral efforts are needed to target NCD risk factors among adolescents to mitigate disease burden and adverse outcomes in adulthood. Findings could guide policy and programming to reduce NCD burden in the sustainable development era.

A Quantitative Point-of-Need Assay for the Assessment of Vitamin D3 Deficiency.

Vitamin D is necessary for the healthy growth and development of bone and muscle. Vitamin D deficiency, which is present in 42% of the US population, is often undiagnosed as symptoms may not manifest for several years and long-term deficiency has been linked to osteoporosis, diabetes and cancer. Currently the majority of vitamin D testing is performed in large-scale commercial laboratories which have high operational costs and long times-to-result. Development of a low-cost point-of-need assay could be transformative to deficiency analysis in limited-resource settings. The best biomarker of vitamin D status, 25hydroxyvitamin D3 (25(OH)D3), however, is particularly challenging to measure in such a format due to complexities involved in sample preparation, including the need to separate the marker from its binding protein. Here we present a rapid diagnostic test for the accurate, quantitative assessment of 25(OH)D3 in finger-stick blood. The assay is accompanied by a smartphone-assisted portable imaging device that can autonomously perform the necessary image processing. To achieve accurate quantification of 25(OH)D3, we also demonstrate a novel elution buffer that separates 25(OH)D3 from its binding protein in situ, eliminating the need for sample preparation. In human trials, the accuracy of our platform is 90.5%.

IDENTIFYING CANCER SPECIFIC METABOLIC SIGNATURES USING CONSTRAINT-BASED MODELS.

Cancer metabolism differs remarkably from the metabolism of healthy surrounding tissues, and it is extremely heterogeneous across cancer types. While these metabolic differences provide promising avenues for cancer treatments, much work remains to be done in understanding how metabolism is rewired in malignant tissues. To that end, constraint-based models provide a powerful computational tool for the study of metabolism at the genome scale. To generate meaningful predictions, however, these generalized human models must first be tailored for specific cell or tissue sub-types. Here we first present two improved algorithms for (1) the generation of these context-specific metabolic models based on omics data, and (2) Monte-Carlo sampling of the metabolic model ux space. By applying these methods to generate and analyze context-specific metabolic models of diverse solid cancer cell line data, and primary leukemia pediatric patient biopsies, we demonstrate how the methodology presented in this study can generate insights into the rewiring differences across solid tumors and blood cancers.

An assessment of student experiences and learning based on a novel undergraduate e-learning resource.

Purpose/objectives The aims of this study were to describe the development of a novel e-learning resource and to assess its impact on student learning experiences and orthodontic knowledge.Methods Thirty-two 4th year dental undergraduate students at Queen Mary University of London were randomly allocated to receive electronic access to e-learning material covering various undergraduate orthodontic topics over a 6-week period. Thirty-one control students were not given access during the study period. All students were asked to complete electronic quizzes both before (T0) and after (T1) the study period and a general questionnaire concerning familiarity with e-learning. The test group also completed a user satisfaction questionnaire at T1. Two focus groups were also undertaken to explore learners' experiences and suggestions in relation to the resource.Results The mean quiz result improved by 3.9% and 4.5% in the control and test groups, respectively. An independent t-test, however, demonstrated a lack of statistical significance in knowledge gain between control and test groups (P = 0.941). The qualitative feedback indicated that students believed that use of the resource enhanced knowledge and basic understanding with students expressing a wish to ingrain similar resources in other areas of undergraduate teaching.Conclusions Use of the novel orthodontic e-resource by 4th year undergraduate students over a 6-week period did not result in a significant improvement in subject knowledge. However, the e-learning has proven popular among undergraduates and the resources will continue to be refined.

The CanPain SCI Clinical Practice Guideline for Rehabilitation Management of Neuropathic Pain after Spinal Cord: recommendations for model systems of care.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The project objectives were to develop the first Canadian recommendations on a model of care for the management of at- and below-level neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: On the basis of a review of the Accreditation Canada standards, the Steering Committee developed questions to guide the CanPainSCI Working Group when developing the recommendations. The Working Group agreed on recommendations through a consensus process. RESULTS: The Working Group developed five recommendations for the organization of neuropathic pain rehabilitation care in people with SCI. CONCLUSIONS: The Working Group recommendations for a model of care for at- and below-level neuropathic pain after SCI should be used to inform clinical practice.

Assessment of thymus size in healthy term neonates using sonography - A study from tertiary care hospital of Central India.

OBJECTIVE: A cross-sectional study was done to assess the size of thymus in term healthy infants using sonography and to assess its variation in size, shape, location, echogenicity and echotexture for both male and female reference population. MATERIAL AND METHODS: A total of 250 term healthy neonates of either sex were subjected to thymic sonography. The shape, size in maximal anteroposterior, longitudinal, and transverse dimensions of both right and left lobes of thymus was evaluated. Their echotexture and echogenicity were determined and standards for reference population were calculated. The results were statistically evaluated. RESULTS: According to the shape; the thymus was quadrilateral in 156 neonates (62%), round in 37 (15%), bilobate in 32 (13%), and crescent shaped in 25 (10%) in transverse scan. According to the echo texture, the thymus echogenicity was homogeneous and almost similar or slightly less to that of the liver and spleen in most cases 200 [80%] and was coarse in 50 (20%). In all subjects, the echogenicity of the thymus was less than that of the thyroid gland. Variations in location of the thymus were found in 70 (28%) neonates. The range of mean AP diameter was 0.39-2.36 cm (mean 1.43 ± 0.3), that of transverse 1.4 - 4.3 cm (mean 2.16 ± 0.54) and that of thymic index 1.2-5.1 cm2 (mean 2.98 ± 0.64). CONCLUSIONS: A normative range was calculated for standard population, which can be used as a reference for comparing thymus size for both normal and diseased neonates for various immunological diseases.

The impact of parenteral nutrition preparation on bloodstream infection risk and costs.

BACKGROUND: Catheter-related bloodstream infections (BSIs) are a serious problem leading to increased morbidity, longer hospital stay, and hence, additional costs. This study evaluated the risk of BSI and the cost of parenteral nutrition (PN) in Germany. SUBJECTS/METHODS: A retrospective observational chart review of patients hospitalized from October 2009 to April 2011 and receiving PN via ready-to-use three-chamber bag (MCB), single bottle (SB) or hospital compounded admixture (CPN) was conducted across Germany. Propensity score-adjusted models were used to evaluate the association between the type of PN, BSI (Cox Proportional Hazards) and hospitalization cost (generalized linear models) within a subgroup receiving all three macronutrients (lipids, amino acids, glucose). RESULTS: Of the 1995 patient records reviewed (MCB=816; CPN=584; SB=595), 1457 patients received all three macronutrients. After adjustment, SB was associated with an increased hazard of BSI, vs MCB without additions (hazard ratio (HR) (95% confidence interval (CI))=2.53 (1.66-3.86)) in the total cohort. Adding supplements to MCB on the ward also increased the BSI risk in both total and subgroup analyses. In patients receiving all three macronutrients, adjusted total costs were MCB (no additions): \[euro]6,572 (95% CI: \[euro]6,896-6263); CPN: \[euro]6,869 (\[euro]7,283-6479); SB: \[euro]6,872 (\[euro]7,242-6521); MCB (ward additions): \[euro]7,402 (\[euro]7,878-6955); P<0.001; P<0.001. CONCLUSION: Use of MCB does not appear to increase treatment costs, possibly by reducing the risk of infection. This study identified several PN preparation methods associated with a significantly increased hazard for BSI; definitive CPN findings are limited by our inability to distinguish automated from manual pharmacy compounding.

A single-centre cost comparison analysis of collagenase injection versus surgical fasciectomy for Dupuytren's contracture of the hand.

BACKGROUND AND AIM: The options for treating patients with Dupuytren's contracture have broadened with the introduction of collagenase. Although the literature would suggest that collagenase treatment is effective, has few complications and is popular with patients, it has not been widely commissioned by the National Health Services of the United Kingdom and other European countries due to concerns about cost. The aim of this study was to compare the cost of surgical fasciectomy to collagenase injections for the treatment of Dupuytren's contracture in a single centre. METHOD: Prospective data on 40 patients undergoing fasciectomy or collagenase injection (20 patients in each group) were collected between January and March 2013. Financial data on the costs of the procedures, equipment, theatre time and follow-up appointments were calculated. RESULTS: The average cost of an open partial fasciectomy pathway was £ 7115.34 and that of a collagenase pathway was £ 2110.62. Eight collagenase patients had physician-led follow-up appointments and only three had hand physiotherapy appointments. By contrast, every fasciectomy patient had at least one physician and one physiotherapist follow-up appointment routinely. CONCLUSION: The results of this study demonstrate that collagenase treatment for Dupuytren's contracture of a single digit in selected patients is just over £ 5000 less than treatment for the same condition using surgical fasciectomy. Collagenase-treated patients require much less physician- and physiotherapist-led postoperative follow-up.

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

Diagnostic value of the rapid assessment of postural instability in Parkinson's disease (RAPID) questionnaire.

BACKGROUND: People with idiopathic Parkinson's disease (PD) develop postural instability in the later stages of the ailment. Postural instability has traditionally been quantified with the Pull test even though its face validity is limited. We previously established cut-off scores for a three-part rapid assessment of postural instability (RAPID) questionnaire as a non-physical complement to the physical test. In the current study, the questionnaire was administered to a new group of PD subjects to evaluate the diagnostic value of the instrument. METHODS: Sensitivity and specificity values were calculated for single and combined sections of the questionnaire by using the Pull test as the gold standard for assessing the presence of postural instability. RESULTS: The questionnaire when used in its entirety gave the highest sensitivity (.71), whereas specificity was highest in the activities of daily living (.74) and fear of falling sections (.74). Net specificity decreased to .44 when the scores from the three sections of the questionnaire were combined. CONCLUSIONS: The high sensitivity of the RAPID questionnaire suggests that it may be used as an adjunct to the Pull test or solely if it is not convenient or contraindicated. The questionnaire may also be adapted for use via the telephone or internet. The limitation of the Pull test in revealing postural instability may explain the low specificity of the questionnaire, i.e. the questionnaire correctly identifies patients as unstable when the Pull test indicates normal postural control. It is hoped that the rapid identification of postural instability in PD may lead to increased awareness of the disease progression and fewer falls.

Current concepts on the management of tooth wear: part 1. Assessment, treatment planning and strategies for the prevention and the passive management of tooth wear.

The aim of this series of four articles on tooth wear management is to provide the reader with the necessary information in order to be able to successfully manage cases of tooth wear, regardless of the cause, severity and location of the wear pattern seen. The content will largely focus on contemporary clinical techniques, illustrated where possible by case examples. Emphasis will be placed on 'additive adhesive techniques' utilising fixed prosthodontic protocols; however, cases of tooth wear amongst partially dentate patients involving the use of removable prostheses will also be described. The importance of patient consent and contingency planning will also be discussed. Paper 1 will describe the assessment of the wear patient, including the rationale for the planning of dental care. Also discussed will be the administration of preventative and passive management strategies for cases displaying tooth wear.

Rapid assessment of postural instability in Parkinson's disease (RAPID): a pilot study.

BACKGROUND: The Fahn's pull (or retropulsion) test is an item in the motor section of the Unified Parkinson's Disease Rating Scale, which is used almost exclusively to classify postural instability in Parkinson's disease (PD). However, the test is hard to standardize and is often performed incorrectly, making it hard to interpret. Moreover, it may not be safe to administer in patients who experience pain in the shoulders, neck, trunk and/or lower extremities. Identifying and grading postural instability in PD without requiring a physical challenge would not only be useful for the clinician but would assist patients and caregivers in its recognition. We propose the use of the rapid assessment of postural instability in Parkinson's disease (RAPID) questionnaire as a non-physical assessment tool. METHODS: We determined the associations between the pull test and items on a risk-assessment questionnaire that consisted of three parts: activities of daily living, fear of falling, and frequency of falling. RESULTS: Significant correlations were found between the pull test and the predictor variables, which ranged between 0.51 and 0.56 whilst the correlations amongst the predictor variables ranged between 0.58 and 0.70. The three parts of the questionnaire, when used in combination, produced a 96% sensitivity in the classification of postural instability. CONCLUSIONS: The RAPID questionnaire can be used as an adjunct to the pull test or solely if the pull test is contraindicated. It may also be possible to administer the questionnaire via the telephone or Internet. It is hoped that the rapid identification of postural instability would lead to fewer falls.

Lipid-soluble vitamins A, D, and E in HIV-infected pregnant women in Tanzania.

BACKGROUND/OBJECTIVES: There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. SUBJECTS/METHODS: This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. RESULTS: Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). CONCLUSIONS: Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions.

Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) affects the quality of life (QoL) and the ability to perform the activities of daily living (ADLs) in patients with systemic sclerosis (SSc). We determined whether the Health Assessment Questionnaire-Disability Index (HAQ-DI), a self-assessment measure of function, correlates with a patient's PAH status in a population of SSc patients with PAH. METHODS: Forty-one patients from one centre with systemic scleroderma, dyspnea and PAH were included. All patients filled in a HAQ-DI, and underwent evaluation with pulmonary function tests (PFTs), 6-minute walk distance (6MWD), degree of dyspnea (Borg dyspnea index), NYHA functional class, and expert PAH physician global assessment every 6 months. Change in HAQ DI was studied to determine relationship to changes in PAH. RESULTS: The HAQ-DI scores had no significant correlation with PAH, including NYHA functional class (r=0.38, p=0.39), Borg dyspnea index (r=0.60, p=0.37), 6MWD (r=-0.04, p=0.86), % predicted DLCO (r=0.31, p=0.25), % predicted FVC (r=0.02, p=0.93), and expert PAH physician global assessment (r=0.06, p=0.97). CONCLUSION: HAQ-DI is not an adequate measure of PAH status in SSc patients with PAH. Although PAH causes severe morbidity and death, changes in PAH severity were not reflected in an overall functional status change as assessed by the HAQ-DI. Thus, HAQ-DI changes do not reflect PAH status in SSc.

Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study.

BACKGROUND: Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9-7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India METHODS: A prospective, observational study of adult patients carried out over a 6 week period in 2005. The prevalence of ADRs, their economic burden from the hospital perspective, severity, and preventability were assessed using standard criteria. RESULTS: A total 6899 patients presented during the study period. Of these, 2046 were admitted for various reasons. A total of 265/6899 patients had ADRs (3.84 %). A total of 141/265 was admitted due to ADsR, and thus ADRs as a cause of admissions were 6.89% of total admissions. A majority (74.71%) were found to be of moderate severity. The most common ADRs were anti-tubercular drug induced hepatotoxicity, warfarin toxicity and chloroquine induced gastritis. The median duration of hospitalization was 5 days [95% CI 5.37, 7.11], and the average hospitalization cost incurred per patient was INR 6197/- (USD 150). Of total ADRs, 59.62% (158/265) were found to be either definitely or potentially avoidable. CONCLUSION: The study shows that ADRs leading to hospitalization are frequent and constitute a significant economic burden. Training of patients and prescribers may lead to a reduction in hospitalization due to avoidable ADRs and thus lessen their economic burden.

Functional assessment of immune markers of graft rejection: a comprehensive study in live-related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for the development of potential therapeutic strategies and also individualization of immunosuppression. The objective of this study is to analyze the clinical relevance of immune parameters such as antidonor antihuman leukocyte antigen (anti-HLA) antibodies, monitoring of cytokines and their receptors on the graft outcome following live-related donor renal transplantation. Flow cytometry-based methods were used to detect antidonor antibodies (flow cytometry crossmatch, FCXM) and intracellular cytokines. Enzyme-linked immunosorbent assay (ELISA) methods were employed to detect anti-HLA class I and class II antibodies and quantitative serum-soluble interleukin-2 receptor (sIL-2R) levels. The data revealed that patients with HLA class I-specific IgG antibody experienced higher acute rejection (AR) episodes at 1 yr in comparison to the antibody negative group (82% vs. 56%, p = 0.01). On the contrary, donor-specific class II antibodies (B+) did not have any influence on the graft survival. However, 15 recipients having both T- and B-cell antidonor antibodies (T+B+) had significantly poor graft survival (60%) as compared to the antibody-negative group (T-B-, 82%, p = 0.05). Additionally, patients having non-donor but HLA-specific antibodies (FCXM-/ELISA+) had poor graft survival as compared to the antibody-negative group (64% vs. 88%, p < 0.05). Further, patients undergoing AR episodes had significantly higher expression of IFN-gamma-producing T cells (19.16 +/- 7.4% median 17.50) as compared to their pre-transplant levels (5.68 +/- 1.63%, Median 5.20) and the non-rejecter group (5.97 +/- 4.39%, median 4.3, p = 0.0004). Similarly sIL-2 was significantly increased in AR episodes during the first month of transplantation (292 +/- 131.5 pmol/L) as compared to those with well-functioning grafts (p = 0.01) and healthy controls (p = 0.001). Evaluation of antidonor antibodies by flow cytometry is found to be relatively more sensitive and a better predictor of graft outcome. Further monitoring of cytokine expression profile of primed peripheral T-helper cells and quantitative analysis of sIL-2R offer additional valuable diagnostic and prognostic tools for follow-up of transplant subjects and a better alternative for functional assessment of immunosuppression.