Implementation of a Problem-Based Presentation Format to Improve Residents' Ambulatory Patient Presentations.

Background: The format for residents to present hospitalized patients to teaching faculty is well defined; however, guidance for presenting in clinic is not uniform. Objective: We report the development, implementation, and evaluation of a new standardized format for presenting in clinic: the Problem-Based Presentation (PBP). Methods: After a needs assessment, we implemented the format at the teaching clinics of our internal medicine residency program. We surveyed participants on innovation outcomes, feasibility, and acceptability (pre-post design; 2019-2020; 5-point scale). Residents' primary outcomes were confidence in presentation content and presentation order, presentation efficiency, and presentation organization. Faculty were asked about the primary outcomes of resident presentation efficiency, presentation organization, and satisfaction with resident presentations. Results: Participants were 111 residents and 22 faculty (pre-intervention) and 110 residents and 20 faculty (post-intervention). Residents' confidence in knowing what the attending physician wants to hear in an outpatient presentation, confidence in what order to present the information, and how organized they felt when presenting in clinic improved (all P<.001; absolute increase of the top 2 ratings of 25%, 28%, and 31%, respectively). Residents' perceived education in their outpatient clinic also improved (P=.002; absolute increase of the top 2 ratings of 19%). Faculty were more satisfied with the structured presentations (P=.008; absolute increase of the top 2 ratings of 27%). Conclusions: Implementation of a new format for presenting in clinic was associated with increased resident confidence in presentation content, order of items, overall organization, and a perceived increase in the frequency of teaching points reviewed by attending physicians.

Effects of Water Temperature Under Projected Climate Change on the Development and Survival of Enallagma civile (Odonata: Coenagrionidae).

Current climate projections for the Great Plains of North America indicate markedly increased air temperatures by the end of the current century. Because the Great Plains contains >80,000 intermittent wetlands that serve as irreplaceable wildlife habitat, this projected warming may have profound effects throughout a continental-scale trophic network. However, little research has been done to determine how projected warming may affect the growth, development, or survival of even common species in this region. We conducted laboratory warming experiments, using an abundant amphibious predatory insect, Enallagma civile (Hagen, 1861), as a model organism, to determine whether projected warming may affect development or survival. Eggs were collected and reared under four water temperature regimes representing current (26°C) and projected future conditions (32, 38, and 41°C). Nymph body size after each molt, development rate, and deaths were recorded. Elevated water temperatures were found to significantly affect the survivorship of E. civile eggs and nymphs as well as adult body size at emergence: an increase in temperature incurred a decrease in survival and size. Nymphs in the two hotter treatments were smaller and had low survivorship whereas individuals in the cooler temperatures generally survived to adulthood and were larger. Nymphs reared at 32°C experienced accelerated ontogenetic development compared with the other temperatures, going from egg to adult in 26 d. Projected elevated temperatures may, thus, be both advantageous and detrimental, causing concern for aquatic invertebrates in this region in the future.

Immunology Update: Biologics.

Biologics are substances made from a living organism or its products. These include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors), recombinant proteins, and fusion proteins. Biologics often are produced using recombinant DNA technology. For example, monoclonal antibodies are produced by inserting human genes into immortalized cell cultures, which then produce the gene product (ie, an antibody) in large quantity. Another approach is to fuse genetic material from nonhuman sources (eg, mice) with human genetic material. The fused gene is inserted into a tissue culture that produces the gene product (ie, a chimeric monoclonal antibody). Biologics are used to manage many conditions, including malignant and nonmalignant conditions. They are widely used in the treatment of human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-positive breast cancer. They also are used in the treatment of leukemias, lymphomas, and colorectal and lung cancer. Biologics improve outcomes in autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Other uses include erythropoietin for renal failure-associated anemia and the new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for treatment of patients with persistently elevated low-density lipoprotein levels despite statin treatment who are at high risk of cardiovascular events.

Immunology Update: Long-Term Care of Solid Organ Transplant Recipients.

Nearly 31,000 US patients received solid organ transplants in 2015 and the number is increasing. Care of transplant recipients includes management of a variety of common posttransplantation issues. Skin cancers are common because of immunosuppression and require skin examinations at intervals. Patients should be educated about the need to report new skin lesions. The rates of other cancers also are increased, including cancers of the head and neck, lung, esophagus, cervix, and urinary tract. Osteoporosis is common in transplant recipients; monitoring and early therapy are important. Patients should not smoke, and vaccinations should be current except for live-virus vaccines, which are contraindicated in patients with immunosuppression. Family physicians should be familiar with the posttransplantation immunosuppression drugs their patients are taking and know their adverse effects and drug interactions. For example, calcineurin inhibitors (eg, cyclosporine, tacrolimus) can impair renal function and increase rates of hypertension and myocardial ischemia. They also interact with statins, macrolide antibiotics, diltiazem, and other drugs. Interval laboratory testing is required to monitor the health of the transplanted organ (eg, renal function tests for kidney transplants, transaminases for liver transplants). Finally, clinicians should remain alert for development of opportunistic infection.

Immunology Update: Primary Immunodeficiency Diseases.

There are 264 primary immunodeficiencies (PIDs), most of which are rare. They are caused by complement deficiencies, defects in phagocyte function, impaired T-cell function, and/or impaired B-cell function with antibody deficiencies. Most patients with PIDs will present, at varying ages, with frequent infections. These infections can be common respiratory tract infections such as otitis media or pneumonia, or they can be unusual bacterial, fungal, or parasitic infections. Neonatal screening for severe combined immunodeficiency syndrome, one of the most common and serious PIDs, is now performed in most US states, but many PIDs manifest and are detected after birth. Clinicians should be alert for PIDs when patients have unusual or frequent infection and perform a diagnostic evaluation. After ruling out HIV and hepatitis C infection, the next step is to obtain a complete blood count, immunodeficiency panel, and immunoglobulin and complement levels. If results are abnormal, or if a PID is suspected clinically but the diagnosis is not clear, prompt referral to an appropriate subspecialist is indicated. Some PIDs can be managed with stem cell transplantation, and transplantation before the first serious infection is associated with better outcomes. In addition, antimicrobial prophylaxis is indicated for many PIDs patients to prevent opportunistic infections.

Immunology Update: New Vaccines.

A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States.

Typology of Ohio, USA, tree farmers based upon forestry outreach needs.

This study differentiated groups of Ohio tree farmers through multivariate clustering of their perceived needs for forest management outreach. Tree farmers were surveyed via a mailed questionnaire. Respondents were asked to rate, on a 1-7 scale, their informational needs for 26 outreach topics, which were reduced to six factors. Based on these factors, three clusters were identified-holistic managers, environmental stewards, and pragmatic tree farmers. Cluster assignment of individuals was dependent upon a tree farmer's age, acreage owned, and number of years enrolled in the American Tree Farm System. Holistic managers showed a greater interest in the outreach topics while pragmatic tree farmers displayed an overall lesser interest. Across clusters, print media and in-person workshops were preferred over emails and webinars for receiving forest management information. In-person workshops should be no more than 1 day events, held on a weekday, during the daytime, at a cost not exceeding $35. Programming related to environmental influences, which included managing for forest insects and diseases, was concluded to have the greater potential to impact clientele among all outreach factors due to the information being applicable across demographics and/or management objectives.

Cirrhosis: diagnosis, management, and prevention.

Cirrhosis is the 12th leading cause of death in the United States. It accounted for 29,165 deaths in 2007, with a mortality rate of 9.7 per 100,000 persons. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary care physicians share responsibility with specialists in managing the most common complications of the disease, screening for hepatocellular carcinoma, and preparing patients for referral to a transplant center. Patients with cirrhosis should be screened for hepatocellular carcinoma with imaging studies every six to 12 months. Causes of hepatic encephalopathy include constipation, infection, gastrointestinal bleeding, certain medications, electrolyte imbalances, and noncompliance with medical therapy. These should be sought and managed before instituting the use of lactulose or rifaximin, which is aimed at reducing serum ammonia levels. Ascites should be treated initially with salt restriction and diuresis. Patients with acute episodes of gastrointestinal bleeding should be monitored in an intensive care unit, and should have endoscopy performed within 24 hours. Physicians should also be vigilant for spontaneous bacterial peritonitis. Treating alcohol abuse, screening for viral hepatitis, and controlling risk factors for nonalcoholic fatty liver disease are mechanisms by which the primary care physician can reduce the incidence of cirrhosis.

HIV-1 infection of placental cord blood monocyte-derived dendritic cells.

Dendritic cells (DC), the most potent antigen-presenting cells (APC), have been implicated as the initial targets of HIV infection in skin and mucosal surfaces. DC can be generated in vitro from blood-isolated CD14(+) monocytes or CD34(+) hematopoietic progenitor cells in the presence of various cytokines. In this study, we investigated whether monocytes obtained from placental cord blood are capable of differentiation into dendritic cells when cultured with a combination of cytokines - granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). We then examined HIV infection, HIV receptor (CD4, CCR5) expression, and beta-chemokine [macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha, MIP-1beta)] production by placental cord monocyte-derived dendritic cells (MDDC) as compared to that of autologous cord monocyte-derived macrophages (MDM). Monocytes isolated from placental cord blood differentiate into DC after 7 days in culture with the mixture of cytokines, as demonstrated by development of characteristic DC morphology, loss of CD14 expression, and gain of CD83, a marker for mature DC. Mature cord MDDC had significantly lower susceptibility to M-tropic ADA (CCR5-dependent) envelope-pseudotyped HIV infection in comparison to autologous placental cord MDM, whereas there was no significant difference in virus replication in cord MDDC and MDM infected with murine leukemia virus envelope-pseudotyped HIV (HIV receptor-independent). This limited susceptibility of cord MDDC to M-tropic HIV infection may be due to lower expression of CD4 and CCR5 on the cell membrane and higher production of MIP-1alpha and MIP-1beta. These data provide important information toward our understanding of the biological properties of cord MDDC in relation to HIV infection.

Natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents.

This is the first report of natural killer cell enumeration and function in HIV-infected and high-risk uninfected adolescents. We examined the association of demographic characteristics of this cohort with three outcomes: CD16+ cell absolute count, lytic units per peripheral blood mononuclear cell (PBMC), and lytic units per natural killer (NK) cell. We also examined the association of CD4, CD38, and antiretroviral therapy (ART) use with these outcomes in the subset of HIV-infected adolescents. Adolescents participating in an on-going longitudinal study (the REACH study) were sampled for CD16+ cell count and NK function. This cross-sectional analysis was performed on 412 subjects with NK cell data available. HIV-positive males had higher numbers of CD3-/CD16+/CD56+ NK cells than HIV-positive females. However, for the HIV-negative subjects, we did not observe a gender-related effect for absolute NK cell numbers. Gender, however, was a significant covariate for the analysis, using lytic units per PBMC as the unit of measurement, with males showing higher values than females. Age was not a predictive covariate for any of the three assessments of NK cell number and function examined. Our observations concerning the HIV-positive individuals indicate that reduced CD4+ T cell counts were associated with decreased circulating CD3-/CD16+/CD56+ NK cells. We also observed an association between elevation of CD8+/CD38+/DR+ lymphocytes and lower NK lytic units per PBMC. The results of our multivariate models indicate that there is a reduced number of NK cells and reduced lytic units per PBMC in patients receiving single or multidrug antiretroviral therapy. There are changes in circulating NK cell number and function in HIV-infected adolescents, in comparison with high-risk HIV-negative adolescents. The data suggest that these changes may occur early in the course of HIV disease but that quantitative changes continue to occur with advancing depletion of the CD4+ T cell pool.

A canarypox vector-expressing cytomegalovirus (CMV) phosphoprotein 65 induces long-lasting cytotoxic T cell responses in human CMV-seronegative subjects.

The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.

The Ohio Substance Abuse Monitoring Network: constructing and operating a statewide epidemiologic intelligence system.

Working with the Ohio Department of Alcohol and Drug Addiction Services (ODADAS) and researchers at the University of Akron, Wright State University's Center for Interventions, Treatment, and Addictions Research developed the Ohio Substance Abuse Monitoring (OSAM) Network to provide a statewide summary of substance abuse trends. Ten key informants across the state collect qualitative and statistical data on substance abuse trends in their regions and prepare biannual reports. The OSAM network has a rapid response capability through which key informants can investigate special issues related to substance abuse identified by ODADAS and provide policymakers with timely, statewide reports. Within 12 months after operations began, the key informants produced reports on drug abuse trends and rapid response issues for the state. These reports prepared policymakers to respond more effectively to prevention and substance abuse treatment needs.

Measurement of cytokine secretion, intracellular protein expression, and mRNA in resting and stimulated peripheral blood mononuclear cells.

Quantitation of cytokine production is a valuable adjunct to standard immunologic assays in defining several pathologic processes. Nevertheless, there is little agreement about which tissues should be assayed, which type of assay should be performed, and which stimulation protocol should be used. As these types of assays enter the clinical arena, there is need for standardization. There is also a need to maximize the amount of information which may be derived from a single sample. We compared secreted interleukin 4 (IL-4), IL-2, IL-6, tumor necrosis factor alpha (TNF-alpha), and gamma interferon proteins as measured by enzyme-linked immunosorbent assay with intracellular cytokine production (IL-2 and gamma interferon) as detected by flow cytometry and quantitative competitive PCR for IL-2, IL-4, TNF-alpha, and gamma interferon mRNA and cDNA. Results from unstimulated cells and cells stimulated with phorbol myristate acetate, phytohemagglutinin, and phorbol myristate acetate plus phytohemagglutin were compared. All three methodologies detected significant stimulation of cytokine production. The combination of phytohemagglutinin and phorbol myristate acetate was overall the most-potent stimulus.

Patterns of plasma human immunodeficiency virus type 1 RNA response to highly active antiretroviral therapy in infected children.

This study examined the rate of decline in plasma human immunodeficiency virus type 1 (HIV-1) RNA levels to <400 and <50 copies/mL in children receiving highly active antiretroviral therapy (HAART) consisting of efavirenz, nelfinavir, and 1 or 2 nucleoside reverse-transcriptase inhibitors. Children receiving HAART achieved a plasma HIV-1 RNA level <400 copies/mL by a median of 4 weeks after initiation of therapy and a decline to <50 copies/mL by 20 weeks. Baseline plasma HIV-1 RNA levels affected the likelihood of achieving potent and sustained virus suppression, and children whose CD4 lymphocyte counts increased >70 cells/microL by 20 weeks on therapy were more likely to achieve durable virological and immunological benefit. These data provide time frames for virus suppression after the initiation of HAART that should be useful in evaluating the potential efficacy and durability of response of newly instituted combination antiretroviral therapy in HIV-1-infected children.

Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team.

The use of recombinant CD4-IgG2 in pediatric human immunodeficiency virus type 1 (HIV-1) infection was evaluated by single and multidose intravenous infusions in 18 children in a phase 1/2 study. The study drug was well tolerated, and dose proportionality was observed in terms of area under time-concentration curve and peak serum concentration. Acute decreases of >0.7 log(10) copies/mL in serum HIV-1 RNA concentration were seen in 4 of the 6 children treated with 4 weekly 10 mg/kg doses. At 14 days after treatment, 3 children had sustained reductions in serum HIV-1 RNA; the other children had rebounded to baseline levels or above. By 28 days after therapy, the peak HIV-1 cellular infectious units was reduced in all 6 children, including the 2 who had experienced an earlier transient increase in values. Thus, recombinant CD4-IgG2 treatment of HIV-1-infected children appears to be well tolerated and capable of reducing HIV-1 burden.

The pediatric critical care experience at Naval Hospital Guam: suggestions for critical care training during residency.

OBJECTIVES: To determine the critical care experience encountered by three recently graduated military pediatricians at an overseas military hospital and present one model of maximizing allowable critical care training time during residency. METHOD: Retrospective reviews of all admissions to the special care nursery and intensive care unit at U.S. Naval Hospital Guam were performed for a 3-year and a 2-year period, respectively. Age, diagnosis, birth weight (if applicable), level of nursery care, invasive procedures performed in the nursery (endotracheal tube, umbilical artery, and umbilical venous catheter placement), patient outcome, and the need for medical transport were recorded. RESULTS: During a 3-year period, there were 122 admissions to the special care nursery (7.1% of all deliveries). In addition, pediatricians performed a total of 53 invasive procedures on these patients, and 29 infants required medical transport to an off-island neonatal intensive care unit for additional care. During a 2-year period, 70 pediatric patients were admitted to the adult intensive care unit, representing 10.2% of all intensive care unit admissions during this period. Fourteen of these patients required medical transport to an off-island referral hospital. CONCLUSION: Graduating military pediatric residents may be faced with caring for a wide range of critically ill neonatal and pediatric patients depending on their assignment. Residency training programs, with the recent increased emphasis on primary pediatric care, will need to streamline instruction in pediatric critical care to provide maximal benefit to the resident while maintaining compliance with Residency Review Committee guidelines.

T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents: retention of naive T lymphocytes in HIV-infected adolescents. The Adolescent Medicine HIV/AIDS Research Network.

BACKGROUND: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. OBJECTIVE: To assess lymphocyte subsets in HIV-infected and high-risk HIV-negative adolescents. DESIGN: The Reaching for Excellence in Adolescent Care and Health Project of the Adolescent Medicine HIV/AIDS Research Network recruits a cohort of HIV-infected and high-risk HIV-uninfected adolescents, aged 13 to 18 years 364 days, into a study of biomedical and behavioral features of HIV infection as seen in the context of full availability of primary care and HIV-related consultative services. Lymphocyte phenotypes were determined using standard 3-color flow cytometry. SETTING: The Reaching for Excellence in Adolescent Care and Health Project is carried out at 16 clinical sites in 14 urban areas. PARTICIPANTS: T-lymphocyte subsets are reported in 192 HIV-positive and 78 HIV-negative youths. RESULTS: For HIV-positive subjects, the total CD4+ cell count and the percentage of CD4+ cells are decreased when compared with those of the HIV-negative controls (P<.001). The reduction in total CD4+ cells reflects a loss of naive, and memory, CD4+ cells compared with HIV-negative youths. Human immunodeficiency virus-infected adolescents, many of whom have been infected recently (ie, those with CD4+ cell counts > or =0.500 x 10(9)/L [500/microL]), have a significant increase in naive CD8+ cells compared with HIV-negative youths (P<.01). There also is a significant increase in memory CD8+ cells at all strata of total CD4+ cells compared with HIV-negative youths (P<.01). The increase in naive CD8+ cells in those subjects with CD4+ cell counts of 0.500 x 10(9)/L or greater is a unique finding in this cohort. CONCLUSIONS: This study demonstrates high levels of naive CD8+ cells in response to HIV infection in adolescents with CD4+ cell counts of 0.500 X 10(9)/L or greater. The presence of high levels of naive CD8+ cells suggests functioning thymic tissue in some adolescents infected with HIV. Furthermore, the normal level of naive CD4+ cells in adolescents with CD4+ levels of 0.500 x 10(9)/L or greater provides additional support for the concept of a more robust immune system in HIV-infected adolescents compared with HIV-infected adults. These observations suggest that the immune system of HIV-infected adolescents may be capable of better responses to neoantigens and cytotoxic T-lymphocyte responses to HIV than the immune system of infected children or adults. Human immunodeficiency virus-infected adolescents may have an immune system that is capable of reconstitution following highly active antiretroviral therapy.

Inhibition of HIV-1 replication in chronically infected cell lines and peripheral blood mononuclear cells by retrovirus-mediated antitat gene transfer.

Among potential genetic targets for intervention in the HIV-1 life cycle, the tat gene product is a key target. We investigated the ability of an antitat gene to inhibit HIV-1 activation and replication in chronically infected promonocyte (U1) and T cell (ACH-2) lines in vitro. U1 and ACH-2 cells were transduced with an antitat gene expressing RNA with dual (polymeric Tat activation response element and antisense-tat) function that interferes with HIV-1 replication. Tumor necrosis factor-alpha (TNF-alpha) plus phorbol 12- myristate 13-acetate (PMA)-induced HIV-1 expression, as determined by reverse transcribed PCR and reverse transcriptase (RT) assays, was significantly inhibited in U1 and ACH-2 cells transduced with the antitat gene, compared with the cells transduced with control vector and untransduced cells. This resistance to TNF-alpha plus PMA-induced HIV-1 expression was demonstrated in antitat gene-transduced U1 and ACH-2 cells maintained in G418-free media for 5 months, suggesting that functional antitat gene may persist for many months in transduced cells and their progeny. Most importantly, we demonstrate that the antitat gene, when introduced into peripheral blood mononuclear cells (PBMC) isolated from patients with HIV-1 infection, inhibited TNF-alpha plus PMA-induced viral replication as determined by RT-PCR and RT activity. In addition, the antitat gene enhanced the survival of CD4+ T lymphocytes from such patients. These data suggest the feasibility of utilizing antitat gene therapy to block activation and replication of HIV-1 in latently infected monocytes and T- lymphocytes in vivo. Gene Therapy (2000) 7, 321-328.