University students and study habits.

OBJECTIVES: The objective of this study was to understand the variables or study habits that inform study in undergraduate and postgraduate students attending Trinity College Dublin. METHODS: A descriptive, cross-sectional anonymous online survey was used to gather data to explore student study habits. Survey 1 was completed by participants in April 2019 and survey 2 was completed by participants in April 2020, during the COVID-19 restrictions. RESULTS: A total of 1557 participants completed survey 1 in 2019, and 1793 participants completed survey 2 in 2020. In both surveys a majority reported using caffeine, library study, sleep pattern adjustment and excercise to aid academic performance. Survey 2 participants reported COVID-19 resulted in increased difficulty studying (91%). In particular loss of structure and routine was negatively impacted by the pandemic (92%), and increased feelings of stress were reported (75%). CONCLUSIONS: Our study suggests a potential role of the college environment as a target for the implementation of interventions to promote student learning, healthy study habits and well-being. The global pandemic has resulted in additional challenging demands for universities to serve an essential role in supporting college students study habits.

Second opinion reporting in head and neck pathology: the pattern of referrals and impact on final diagnosis.

OBJECTIVE: There is a need for second opinion histopathology referrals, especially for patients with head and neck pathology. The objective of this study was to determine the pattern and potential impact of referrals to a specialist oral and maxillofacial pathologist. STUDY DESIGN: Retrospective analysis of 566 consecutive referrals with demographic and clinical information was performed. The original diagnosis and the specialists' second opinion diagnosis were compared to assess for discrepancies and potential effect on patient management. RESULTS: Seventy-five percent of cases were referred by general pathologists. Salivary gland (30%) and odontogenic tumors (12%) were the most commonly referred categories. Of the referred cases, 58 (9%) resulted in a significant change in diagnosis, impacting patient management. In 24 cases (4%) the diagnosis was revised from benign to malignant, and in 22 (4%) from malignant to benign. CONCLUSION: This study highlights the need for referrals to oral and maxillofacial pathologists. A second opinion may assist in accurate diagnosis and patient management.

Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT).

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

What are RBC-transfusion-dependence and -independence?

The term RBC-transfusion-dependence is widely-used by hematologists to describe a condition of severe anemia typically arising when erythropoiesis is reduced such that a person continuously requires ≥1 RBC-transfusions over a specified interval. Defining a person as RBC-transfusion-dependent has important implications in diverse hematological disorders especially because it strongly-correlated with decreased survival. Conversely, becoming RBC-transfusion-independent or receiving fewer RBC-transfusions over a specified interval is defined as improvement or response in many disease- and/or therapy-setting. Whether this correlates with improved survival is controversial. We used a structured expert-panel consensus panel process to define RBC-transfusion-dependence and -independence or improvement. We suggest these definitions may prove useful to persons studying or treating these diseases.

The RhoA transcriptional program in pre-T cells.

The GTPase RhoA is essential for the development of pre-T cells in the thymus. To investigate the mechanisms used by RhoA to control thymocyte development we have used Affymetrix gene profiling to identify RhoA regulated genes in T cell progenitors. The data show that RhoA plays a specific and essential role in pre-T cells because it is required for the expression of transcription factors of the Egr-1 and AP-1 families that have critical functions in thymocyte development. Loss of RhoA function in T cell progenitors causes a developmental block that pheno-copies the consequence of losing pre-TCR expression in Recombinase gene 2 (Rag2) null mice. Transcriptional profiling reveals both common and unique gene targets for RhoA and the pre-TCR indicating that RhoA participates in the pre-TCR induced transcriptional program but also mediates pre-TCR independent gene transcription.

Nuclear localization of HIV-1 tat functionalized gold nanoparticles.

The impermeable nature of the cell plasma membrane limits the therapeutic uses of many macromolecules and there is therefore a growing effort to circumvent this problem by designing strategies for targeted intracellular delivery. During the last decade several cell penetrating peptides, such as the HIV-1 tat peptide, have been shown to traverse the cell membrane, where integral protein transduction domains (PTDs) are responsible for their cellular uptake, and to reach the nucleus while retaining biological activity. It has since been discovered that PTDs can enable the cellular delivery of conjugated biomolecules and even nanoparticles, but nuclear delivery has remained problematic. This present study focuses on the development of water soluble, biocompatible gold nanoparticles of differing size functionalized with the HIV-1 tat PTD with the aim of producing nuclear targeting agents. The particles were subsequently tested in vitro with a human fibroblast cell line, with results demonstrating successful nanoparticle transfer across the plasma membrane, with 5 nm particles achieving nuclear entry while larger 30 nm particles are retained in the cytoplasm, suggesting entry is blocked via nuclear pores dimensions.

Orthodontic retention: why when and how?

Retention is normally required after active orthodontic tooth movement to hold the teeth in their new positions. This article reviews the principles of orthodontic retention and describes common retention regimes and appliances.

Frequency of occupational health concerns in general clinics.

Studies have suggested that occupational disease and injury are under-recognized by clinicians. To estimate the frequency of occupational factors in disease and injury, 108 patients in a general (not occupational) health care facility were interviewed about the frequency and types of workplace-health interactions. Thirty-nine percent reported possible causation by work, and 66% reported a possible increase in symptoms by work, even if not caused by work. Twenty-seven percent reported changing jobs and/or tasks because of work-health interactions. The majority of men and women reported that worksite changes could improve their functional ability at work. This study therefore indicates that (1) occupational health concerns are common in primary care clinics, even if not addressed by clinicians; (2) the definition of occupational health concerns should be broadened to include disease caused by work, disease symptoms worsened by work, and the need for occupational accommodation even if the disease itself is not caused by work; and (3) inquiring about patient concerns about workplace-health interactions can provide clinicians with significant opportunities for primary, secondary, and tertiary prevention.

A simple institutional educational intervention to decrease use of selected expensive medications.

OBJECTIVE: To determine whether a simple educational intervention can influence use of prescription medications at an institution. DESIGN: Cost-effectiveness analysis of prescribing behavior before and after an educational intervention. SETTING: A large, urban, free-standing academic rehabilitation hospital. PARTICIPANTS: Physicians, residents, and physician extenders. INTERVENTIONS: The hospital's pharmacy department provided simple written educational material about cost differences of various prescription medications to attending and resident physicians, nurse leaders, and case managers. Telephoned reminders were given when targeted medications were prescribed. MAIN OUTCOME MEASURES: Total prescription medication use was recorded monthly for 12 months before and after the intervention. Pharmaceuticals monitored were subcutaneously administered anticoagulants, histamine type 2 (H2) blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs). RESULTS: A 32% decrease in use of the more costly anticoagulant and a 20% increase in use of the less costly anticoagulant (p <.0001), representing an estimated annual savings of nearly $66,000. Use of more costly H2 antagonist decreased 50% and use of less costly H2 antagonist increased 128% (p <.0001). With written intervention only, use of more costly NSAIDs declined 28%, whereas use of less costly NSAIDs increased 58% (p <.0020). CONCLUSION: Providing physicians with simple pharmaceutical cost information and telephone reminders decreased the use of targeted more costly medications.

Kinematic magnetic resonance imaging of the effect of bracing on patellar position: qualitative assessment using an extremity magnetic resonance system.

OBJECTIVE: To use an extremity magnetic resonance system to perform kinematic magnetic resonance imaging (MRI) of the patellofemoral joint to qualitatively assess the effect of bracing on patellar position. DESIGN AND SETTING: Subjects underwent kinematic MRI of the symptomatic extremity with a 0.2-Tesla extremity magnetic resonance system. Images were obtained using a knee coil and a T1-weighted, spin echo pulse sequence. SUBJECTS: Seven female patients with patellofemoral joint symptoms. MEASUREMENTS: FOUR DIFFERENT AXIAL SECTIONS WERE OBTAINED FOR EACH POSITION: extension and 3 positions of flexion up to 36 degrees . An appropriate-sized patellofemoral brace was applied, and the kinematic MRI procedure was repeated. RESULTS: Six patients had lateral displacement of the patella, and 1 patient had medial displacement of the patella. After application of the brace, 6 patients (5 with lateral displacement and 1 with medial displacement, 86%) exhibited correction (5) or improvement (1 with lateral displacement) in the abnormal patellar positions, and 1 patient had worsening of the abnormal position of the patella. CONCLUSIONS: We used kinematic MRI to determine the presence of abnormal patellar positioning. Application of the brace counteracted the abnormal patellar positions in most of the patients studied.

Feasibility of cellular adoptive immunotherapy for Epstein-Barr virus-associated lymphomas using haploidentical donors.

Epstein-Barr virus (EBV)-associated lymphomas following bone marrow or solid organ transplantation are often sensitive to immunomodulatory therapies. These have included withdrawal or reduction in immunosuppressive therapy in the solid organ transplant setting and adoptive cellular therapies in the bone marrow transplant (BMT) setting. We describe a strategy for generating EBV-specific cytotoxic T cell therapy lines with substantial killing activity against haploidentical targets. Weekly stimulation of peripheral blood mononuclear cells (PBMCs) for 3 weeks with the irradiated cells of an autologous EBV-transformed B lymphoblastoid cell line (B-LCL), followed by stimulation in the presence of IL-2, yielded T cell lines that were cytolytic for haploidentical B-LCLs but did not lyse haploidentical targets not expressing EBV antigens.

The effects of triamcinolone acetonide aqueous nasal spray on adrenocortical function in children with allergic rhinitis.

BACKGROUND: Suppression of adrenocortical function, a risk associated with oral corticosteroids, is minimized with intranasal corticosteroids. Triamcinolone acetonide (TAA) aqueous nasal spray, at therapeutic doses, has no measurable effect on adrenocortical function in adults with allergic rhinitis. OBJECTIVE: This double-blind, placebo-controlled study compared the effect of once-daily TAA aqueous nasal spray (220 or 440 microg) with placebo on adrenocortical function after 6 weeks of treatment in pediatric (children 6 to 12 years of age) patients with allergic rhinitis. The pharmacokinetic profile of TAA was examined after once-daily intranasal administration of TAA aqueous nasal spray 440 microg for 6 weeks. METHODS: Eighty children received TAA aqueous nasal spray 220 microg or 440 microg or placebo for 6 weeks. Adrenocortical function was assessed by analyzing plasma cortisol levels before stimulation (0 hour) and at 30 and 60 minutes after a rapid 1-hour intravenous cosyntropin stimulation test performed before treatment and after 6 weeks of treatment. Samples for pharmacokinetic evaluation were collected from 19 patients at baseline (0 hour) and at 0.5, 1, 1.5, and 6 hours after the final dose of study medication. RESULTS: After 6 weeks, no significant effects on adrenocortical function were observed at 30 or 60 minutes after cosyntropin stimulation with either dose of TAA aqueous nasal spray. TAA concentrations in plasma showed rapid elimination of the drug, with little or no accumulation. CONCLUSIONS: TAA aqueous nasal spray (220 or 440 microg/day) has no measurable effect on adrenocortical function in pediatric patients with allergic rhinitis. Pharmacokinetic parameters after 440 microg/day of TAA aqueous nasal spray indicate a rapid decline of plasma drug levels, with little or no systemic accumulation of study drug.

Disposition of a novel recombinant antithrombotic agent, RG 12986, in cynomolgus monkeys.

RG 12986, a novel antagonist of platelet aggregation, is a recombinant peptide based on the sequence in von Willebrand factor, which contains the GP1b binding site. Disposition of the peptide in cynomolgus monkeys was determined using nonlabeled and 35S-labeled product. After iv administration, the peptide underwent a triphasic decay in the plasma. The first phase of elimination, after distribution, had a t1/2 (approximately 20 min) similar to that observed for inhibition of platelet aggregation (approximately 25 min). The correlation between the logarithm of the plasma peptide concentration and activity was r = 0.9989. The effective duration of pharmacological activity was approximately 2 hr. After this period, a slower terminal phase of plasma elimination was observed (t1/2 approximately 2 hr). Plasma clearance (7-15 ml/min/kg) and volume of distribution at steady-state (0.4-0.9 L/kg) estimates appeared to have a slight dose dependency, but the scope of the investigation did not allow this to be verified. There was a linear correlation between dose and AUC (r2 = 0.9998), but for each 4-fold increase in dose there was a greater than 4-fold increase in AUC. Immediately after iv administration, significant fragmentation of the peptide was observed with polyacrylamide gel electrophoresis analysis of the plasma. This initial rate of metabolism was subsequently slowed to t1/2 estimates of 2 hr, followed by a very long terminal half-life of plasma radioactivity of 12 days. It is likely that this terminal half-life represents metabolic recycling of 35S. Elimination of the label was primarily via the kidneys.

Common shoulder injuries among athletes: evaluation and management.

Shoulder injuries in athletics, especially throwing sports, are a relatively common phenomenon. Assessment and evaluation of shoulder problems require a systematic approach that should be both comprehensive and efficient. This article outlines a sequential process of evaluation that incorporates the following different components of a thorough examination: taking a history, inspecting the shoulder, palpating the structures, assessing active and passive range of motion, testing strength, and performing special tests. Guidelines for management of the most common diagnoses are included.

A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema.

Two procedures (laser bullectomy and lung reduction surgery with staples) are currently available for the surgical treatment of patients with diffuse emphysema. We compared the efficacy of these two surgical approaches in 72 patients, aged 67 +/- 7 years (mean +/- standard deviation), who had diffuse emphysema scored as severe on computed tomography and severe fixed expiratory airflow obstruction. The patients were prospectively randomized to undergo either neodymium:yttrium aluminum garnet contact laser surgery (n = 33) or stapled lung reduction surgery (n = 39) by unilateral thoracoscopy. The operative mortalities were 0% and 2.5%, respectively. No significant differences were noted between the groups (p < 0.05) with respect to operating time, hospital days, or air leakage for more than 7 days. However, a delayed pneumothorax developed in six patients (18%) who had laser treatment (p = 0.005). The operations eliminated dependency on supplemental oxygen in 52% of the laser group and 87.5% of the stapled lung reduction group (p = 0.02). The mean postoperative improvement in the forced expiratory volume in 1 second at 6 months was significantly greater for the patients undergoing the staple technique (32.9% vs 13.4%, p = 0.01) than for the laser treatment group.

AIDS prevention research in Chile and implications for the United States.

PIP: Chile holds interest for researchers due to the relatively low but increasing prevalence of human immunodeficiency virus (HIV) and existence of an extensive infrastructure for implementing an affordable acquired immunodeficiency syndrome (AIDS) prevention strategy. To facilitate the development of a pragmatic, affordable AIDS intervention plan for Chile, the following data sources were reviewed: mandatory case reporting data collected by the Chilean Ministry of Health, findings of the Chilean version of the World Health Organization AIDS general population survey, studies of the validity of the official HIV transmission classification system used for national planning purposes, interviews with people with AIDS, and a study of HIV testing in Santiago's health care system. By June 1994, 1016 cases of AIDS had been reported and 1627 people had been identified as HIV-positive. 93% of those with AIDS were men; homosexual/bisexual transmission accounted for 66.2% of cases and heterosexual transmission another 19.4%. In-depth interviews with AIDS patients revealed they were a well-defined population subgroup with few linkages to other sectors. This finding calls into question the current government strategy of broad-based mass media campaigns. Preferable would be campaigns that target homosexual men. A strength of the Chilean primary health care system is its effective utilization of nurses. Nurses manage about 1/3 of clinic visits, with no input from physicians, and their involvement in AIDS prevention should be strengthened.^ieng

Social context variables as predictors of smoking cessation.

OBJECTIVE: To examine positive and negative social support and other selected social context variables (age, education, marital status, gender, and exposure to other smokers inside and outside the home) as predictors of smoking cessation in non-hospitalised adults with diagnosed cardiovascular disease at follow up after one, six, and 12 months. DESIGN: Discriminant function analyses (DFA) and longitudinal "lag" analyses. SUBJECTS: 137 Non-hospitalised adults with diagnosed cardiovascular health problems. RESULTS: Examination of the concurrent DFAs revealed significant univariate F ratios for the predictor variables of gender and marital status at one year and low negative support at all three follow ups. Quitters reported significantly lower levels of negative support than non-quitters over the course of the year and tended to be male and married. Longitudinal "lag" analyses, however, revealed that higher positive social support at one month and higher negative support at six months were both predictive of smoking cessation at one year. At one year more men than women and more married than not married smokers were successful in quitting. No effects for age, education, or exposure to others smoking inside or outside the home were found on any of the concurrent DFAs or longitudinal analyses. CONCLUSION: A series of concurrent DFAs revealed that positive support was a significant predictor of quitting at one year and negative support was predictive of not quitting at all three follow ups. Longitudinal "lag" analyses showed that positive support at one month and negative support at six months both predicted quitting at one year. Being male and married were found to contribute to quitting on both sets of analyses. The effects for positive and negative support on the smoking behaviour of adults with cardiovascular disease tended to change over the course of a year. These findings suggest that positive and negative social support may have differential effects over time. As the smoker moves along the "quitting trajectory" it may be that more "nagging" or negative interactions are needed at some point to get smokers to quit, if positive support has not worked or is not working. Progression of disease also may have served as a stimulus for family members and friends to become more insistent and negative about the person's continued smoking. More research is needed to examine the quitting process to determine which and how social context variables contribute.

Acute and chronic effects of nonsteroidal antiinflammatory drugs on glomerular filtration rate in elderly patients.

To assess the effects of nonsteroidal antiinflammatory drugs (NSAIDs) on glomerular filtration rate (GFR) in elderly patients with and without renal insufficiency, we conducted an open-label, randomized, prospective three-period cross-over study. Twenty-nine patients at least 65 years old were assigned to groups with preserved GFR (> 1.16 mL/s [70 mL/min]) or with renal insufficiency (GFR 0.50-1.16 mL/s [30-70 mL/min]). Patients received 800 mg ibuprofen three times daily, 20 mg piroxicam daily, or 200 mg sulindac twice daily for 1 month. Three-hour inulin and two-day creatinine clearances were measured before and after the first and last doses of NSAIDs. Ibuprofen, piroxicam, and sulindac decreased inulin clearance after single-doses in both groups of patients. In patients with renal insufficiency, creatinine clearance did not change after administration of ibuprofen for 1 month (0 +/- 0.06 mL/s, mean +/- standard error), but was decreased similarly with administration of either piroxicam or sulindac (-0.12 +/- 0.06 mL/s [-7.2 +/- 3.6 mL/min], P < 0.02). One patient with preserved GFR, but with other risk factors for NSAID-associated renal impairment, met our criteria for withdrawal by experiencing at least a 40 mumol/L (0.5 mg/dL) increase in serum creatinine above their baseline value. Our data indicate that NSAIDs do not adversely affect GFR in patients with preserved renal function unless they have another risk factor for NSAID-associated renal impairment. In contrast, patients with renal insufficiency may have significant chronic decrements in GFR with long-acting NSAIDs such as piroxicam and sulindac, but not with short-acting ibuprofen. Such patients should have renal function monitored while being treated with long-acting NSAIDs.

CNS development of health maintenance programs: quality improvement and cost reduction.

Several outpatient health maintenance programs were developed by CNSs that resulted in quality improvement and cost savings. Common implementation strategies, barriers to implementation, marketing issues and techniques, and revenue generation issues were found. An outpatient consultation model was used to expand enterostomal therapy and diabetic teaching services. Education and support programs include a cardiac support group and community education classes on aging. Preadmission programs include physical therapy consultation for patients scheduled for elective orthopedic surgery. Outpatient programs facilitate continuity of care in a managed care format, promote cost savings, and provide unique services that encourage patients to return to our hospital, thereby increasing market share. Key barriers encountered include inconsistent or ambiguous administrative support, budgetary constraints, lack of collaboration, communication problems, facility limitations, funding considerations, resource allocation, and territoriality. The programs are consistent with the change in focus of health care from treatment to prevention.