Development and validation of technologies suitable for the decontamination and re-use of contaminated N95 filtering facepiece respirators in response to the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has brought significant challenges to society globally, particularly in the area of healthcare provision. A pressing need existed in protecting those tasked with delivering healthcare solutions during the COVID-19 crisis by providing solutions for preserving adequate supplies of effective personal protective equipment (PPE). AIM: To evaluate and validate available methods for the decontamination of N95 filtering facepiece respirators (FFRs) while maintaining functionality during re-use. METHODS: Multiple low-temperature steam and vaporized hydrogen peroxide (VHP) technologies were assessed for inactivation of Mycobacterium spp. and feline calicivirus (employed as representatives of the contamination challenge). FINDINGS: Virus (≥3log10) and Mycobacterium spp. (≥6log10) inactivation was achieved on various types of N95 FFRs using an array of heat (65-71oC), humidity (>50% relative humidity) and VHP without affecting the performance of the PPE. CONCLUSION: The methods have been validated and were authorized by the US Food and Drug Administration under a temporary emergency use authorization. Based on the findings, opportunities exist for development and deployment of decontamination methods made from simple, general purpose materials and equipment should a future need arise.

A randomized phase II trial of CRLX101 in combination with bevacizumab versus standard of care in patients with advanced renal cell carcinoma.

BACKGROUND: Nanoparticle-drug conjugates enhance drug delivery to tumors. Gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. CRLX101 is a novel nanoparticle-drug conjugate containing camptothecin, a potent inhibitor of topoisomerase I and the hypoxia-inducible factors 1α and 2α. In a phase Ib/2 trial, CRLX101 + bevacizumab was well tolerated with encouraging activity in metastatic renal cell carcinoma (mRCC). We conducted a randomized phase II trial comparing CRLX101 + bevacizumab versus standard of care (SOC) in refractory mRCC. PATIENTS AND METHODS: Patients with mRCC and 2-3 prior lines of therapy were randomized 1 : 1 to CRLX101 + bevacizumab versus SOC, defined as investigator's choice of any approved regimen not previously received. The primary end point was progression-free survival (PFS) by blinded independent radiological review in patients with clear cell mRCC. Secondary end points included overall survival, objective response rate and safety. RESULTS: In total, 111 patients were randomized and received ≥1 dose of drug (CRLX101 + bevacizumab, 55; SOC, 56). Within the SOC arm, patients received single-agent bevacizumab (19), axitinib (18), everolimus (7), pazopanib (4), sorafenib (4), sunitinib (2), or temsirolimus (2). In the clear cell population, the median PFS on the CRLX101 + bevacizumab and SOC arms was 3.7 months (95% confidence interval, 2.0-4.3) and 3.9 months (95% confidence interval 2.2-5.4), respectively (stratified log-rank P = 0.831). The objective response rate by IRR was 5% with CRLX101 + bevacizumab versus 14% with SOC (Mantel-Haenszel test, P = 0.836). Consistent with previous studies, the CRLX101 + bevacizumab combination was generally well tolerated, and no new safety signal was identified. CONCLUSIONS: Despite promising efficacy data on the earlier phase Ib/2 trial of mRCC, this randomized trial did not demonstrate improvement in PFS for the CRLX101 + bevacizumab combination when compared with approved agents in patients with heavily pretreated clear cell mRCC. Further development in this disease is not planned. CLINICAL TRIAL IDENTIFICATION: NCT02187302 (NIH).

Association of Clinical Events With Everolimus Exposure in Kidney Transplant Patients Receiving Low Doses of Tacrolimus.

A key objective in the use of immunosuppression after kidney transplantation is to attain the optimal balance between efficacy and safety. In a phase 3b, multicenter, randomized, open-label, noninferiority study, the incidences of clinical events, renal dysfunction, and adverse events (AEs) were analyzed at 12 months in 309 de novo renal transplant recipients receiving everolimus (EVR), low-dose tacrolimus (LTac), and prednisone. Cox proportional hazard regression modeling was used to estimate the probability of clinical events at specified combinations of time-normalized EVR and Tac trough concentrations. At 12 months, the highest incidence of treated biopsy-proven acute rejection (tBPAR) and graft loss occurred most often in patients with EVR trough concentration <3 ng/mL (64.7% and 10.5%, respectively). At 1 month and 12 months, increasing EVR levels were associated with fewer tBPAR events (both p < 0.0001). Low estimated glomerular filtration rate (eGFR) and decreased eGFR occurred more often in patients with lower EVR and higher Tac levels. AEs were most often observed in patients with EVR levels <3 ng/mL. This study supports maintaining an EVR trough concentration of 3-8 ng/mL, when combined with LTac, to achieve balanced efficacy and safety in renal transplant recipients. TRIAL REGISTRATION: NCT01025817.

A2 to B Blood Type Incompatible Deceased Donor Kidney Transplantation in a Recipient Infected with the Human Immunodeficiency Virus: A Case Report.

BACKGROUND: With the introduction of the Kidney Allocation System in the United States in December 2014, transplant centers can list eligible B blood type recipients for A2 organ offers. There have been no prior reports of ABO incompatible A2 to B deceased donor kidney transplantation in human immunodeficiency virus-positive (HIV+) recipients to guide clinicians on enrolling or performing A2 to B transplantations in HIV+ candidates. We are the first to report a case of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results. METHODS AND RESULTS: We describe an HIV+ 39-year-old African American man with end-stage renal disease who underwent A2 to B blood type incompatible deceased donor kidney transplantation. Prior to transplantation, he had an undetectable HIV viral load. The patient was unsensitized, with his most recent anti-A titer data being 1:2 IgG and 1:32 IgG/IgM. Induction therapy of basiliximab and methylprednisolone was followed by a postoperative regimen of plasma exchange, intravenous immunoglobulin, and rituximab with maintenance on tacrolimus, mycophenolate mofetil, and prednisone. He had delayed graft function without rejection on allograft biopsy. Nadir serum creatinine was 2.0 mg/dL. He continued to have an undetectable viral load on the same antiretroviral therapy adjusted for renal function. CONCLUSIONS: To our knowledge, this is the first report of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results, suggesting that A2 donor kidneys may be considered for transplantation into HIV+ B-blood type wait list candidates.

Efficacy and Safety of Everolimus Plus Low-Dose Tacrolimus Versus Mycophenolate Mofetil Plus Standard-Dose Tacrolimus in De Novo Renal Transplant Recipients: 12-Month Data.

In this 12-month, multicenter, randomized, open-label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low-dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard-dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti-thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy-proven acute rejection [tBPAR]/graft loss/death/loss to follow-up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [-3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow-up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m2 ) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.

CHALLENGES IN MANAGEMENT OF WARFARIN ANTI-COAGULATION IN ADVANCED HIV/AIDS PATIENTS WITH VENOUS THROMBOTIC EVENTS--A CASE SERIES FROM A RESEARCH CLINIC IN RURAL KERICHO, KENYA.

BACKGROUND: Venous thrombotic events (VTE) occur at high ratesin HIV/AIDS patients and are likely under-diagnosed in rural sub-Saharan Africa. OBJECTIVE: To describe clinical presentations and challenges in the management of VTE in patients with advanced HIV/AIDS. DESIGN: Case series from patients enrolled in a prospective observational cohort study. SETTINGS: A clinical research centre in rural Kericho, Kenya. SUBJECTS: Two hundred patients with median age 38 (30-47) years, BMI 16.9 (12.4-20.3) kg/m2, haemoglobin 9.3 (6.8-13.4) g/dL, CD4+ T-cell count 27 (4-77) cells/mm and plasma HIV RNA 5.23 (3.70-5.88) log10 copies/mL. INTERVENTIONS: VTE cases were diagnosed by clinical presentation and Doppler/ radiographic confirmation. Anti-coagulation therapy was managed by a multidisciplinary team; patients were initiated on enoxaparin or heparin followed by warfarin. RESULTS: Over two years,11patients (5.5%) experienced VTE. All but one (10/11,90.9%) case occurred within six months of starting ART. Nine patients had peripheral VTE (five popliteal, four femoral) and two had cerebral sinus thromboses. VTE was diagnosed 52 (1-469) days after ART initiation, and 81.8% of cases were outpatients at presentation. All patients received at least one concomitant medication that could significantly interact with warfarin (efavirenz, nevirapine, lopinavir/ritonavir, rifampicin, trimethoprim-sulfamethoxazole, and fluconazole). A median of 39 (10-180) days and eight (4-22) additional clinic visits were required to achieve/maintain a therapeutic INR of 2-3. Two minor bleeding complications occurred. No recurrent VTE cases were observed. CONCLUSION: Consideration of VTE and preparedness for management in patients with advanced HIV/AIDS starting ART is critical in sub-Saharan Africa. Overcoming challenges in anti-coagulation is possible in rural settings using a multidisciplinary team approach.

A web-based application for initial screening of living kidney donors: development, implementation and evaluation.

Most centers utilize phone or written surveys to screen candidates who self-refer to be living kidney donors. To increase efficiency and reduce resource utilization, we developed a web-based application to screen kidney donor candidates. The aim of this study was to evaluate the use of this web-based application. Method and time of referral were tabulated and descriptive statistics summarized demographic characteristics. Time series analyses evaluated use over time. Between January 1, 2011 and March 31, 2012, 1200 candidates self-referred to be living kidney donors at our center. Eight hundred one candidates (67%) completed the web-based survey and 399 (33%) completed a phone survey. Thirty-nine percent of donors accessed the application on nights and weekends. Postimplementation of the web-based application, there was a statistically significant increase (p < 0.001) in the number of self-referrals via the web-based application as opposed to telephone contact. Also, there was a significant increase (p = 0.025) in the total number of self-referrals post-implementation from 61 to 116 per month. An interactive web-based application is an effective strategy for the initial screening of donor candidates. The web-based application increased the ability to interface with donors, process them efficiently and ultimately increased donor self-referral at our center.

The nonhomologous end joining factor Artemis suppresses multi-tissue tumor formation and prevents loss of heterozygosity.

Nonhomologous end joining (NHEJ) is a critical DNA repair pathway, with proposed tumor suppression functions in many tissues. Mutations in the NHEJ factor ARTEMIS cause radiation-sensitive severe combined immunodeficiency in humans and may increase susceptibility to lymphoma in some settings. We now report that deficiency for Artemis (encoded by Dclre1c/Art in mouse) accelerates tumorigenesis in several tissues in a Trp53 heterozygous setting, revealing tumor suppression roles for NHEJ in lymphoid and non-lymphoid cells. We also show that B-lineage lymphomas in these mice undergo loss of Trp53 heterozygosity by allele replacement, but arise by mechanisms distinct from those in Art Trp53 double null mice. These findings demonstrate a general tumor suppression function for NHEJ, and reveal that interplay between NHEJ and Trp53 loss of heterozygosity influences the sequence of multi-hit oncogenesis. We present a model where p53 status at the time of tumor initiation is a key determinant of subsequent oncogenic mechanisms. Because Art deficient mice represent a model for radiation-sensitive severe combined immunodeficiency, our findings suggest that these patients may be at risk for both lymphoid and non-lymphoid cancers.

Antidepressants in child and adolescent depression: where are the bugs?

OBJECTIVE: To examine the data on the effect of antidepressant medication in depressed children and adolescents and the causes of the results obtained. METHOD: A systematic literature search was conducted, supplemented by a manual search, and a search of public online information on paediatric antidepressant trials reviewed by regulatory agencies. RESULTS: Data gathered from published and unpublished randomized controlled trials vary in their findings, with most of the studies showing a lack of efficacy characterized by a high placebo response rate. CONCLUSION: Differences from efficacy results with the same drugs in adult depression may be because of neurobiological developmental correlates, developmental differences in pharmacokinetics and pharmacodynamics, high rates of placebo response in children, and a number of methodological influences. There are several areas needing more attention in paediatric antidepressant clinical trials. Judicious use of published and unpublished studies to assess who may benefit from treatment with antidepressants seems warranted.

Characteristics of HIV infected patients cared for at "academic model for the prevention and treatment of HIV/AIDS" clinics in western Kenya.

BACKGROUND: With the new initiatives to treat large numbers of HIV infected individuals in sub-Saharan Africa, policy makers require accurate estimates of the numbers and characteristics of patients likely to seek treatment in these countries. OBJECTIVE: To describe characteristics of adults receiving care in two Kenyan public HIV clinics. DESIGN: Cross-sectional cohort analysis of data extracted from an electronic medical records system. SETTING: Academic Model for the Prevention and Treatment of HIV/AIDS (AMPATH) HIV clinics in Kenya's second national referral (urban) hospital and a nearby rural health center. SUBJECTS: Adult patients presenting for care at HIV clinics. MAIN OUTCOME MEASURES: Gender and inter-clinic stratified comparisons of demographic, clinical, and treatment data. RESULTS: In the first nineteen months, 790 adults visited the urban clinic and 294 the rural clinic. Mean age was 36 +/- 9 (SD) years. Two-thirds were women; a quarter had spouses who had died of acquired immune deficiency syndrome (AIDS). HIV/AIDS behavioural risk factors (multiple sexual partners, rare condom use) and constitutional symptoms (fatigue, weight loss, cough, fever, chills) were common. Rural patients had more symptoms and less prior and current tuberculosis. Men more commonly presented with symptoms than women. The cohort CD4 count was low (223 +/- 197 mm3), with men having significantly lower CD4 count than women (185 +/- 175 vs. 242 +/- 205 p = 0.0007). Eighteen percent had an infiltrate on chest radiograph. Five percent (most often men) had received prior antiretroviral drug therapy, (7% in urban and 1% in rural patients, p = 0.0006). Overall, 393 (36%) received antiretroviral drugs, 89% the combination of lamivudine, stavudine, and nevirapine. Half received prophylaxis for tuberculosis and Pneumocystis jirovecii. Men were sicker and more often received antiretroviral drugs. CONCLUSIONS: Patients presenting to two Kenyan HIV clinics were predominantly female, ill and naive to retroviral therapy with substantial differences by clinic site and gender. Behavioural risk factors for HIV/AIDS were common. A thorough understanding of clinical and behavioural characteristics can help target prevention and treatment strategies.

Calcineurin inhibitor avoidance versus steroid avoidance following kidney transplantation: Postoperative complications.

This study compared early postoperative complications in kidney transplant recipients treated with either a sirolimus-based calcineurin inhibitor (CNI)-free regimen or a tacrolimus-based steroid-free regimen. We used a single-center, prospective, sequential but nonrandomized study design. Consecutive recipients of primary cadaveric or non-HLA identical kidney transplant recipients received either a CNI-free regimen, consisting of sirolimus 5 mg daily beginning postoperative day 3, mycophenolate mofetil 1 gm twice a day, and methylprednisolone 500 mg intraoperatively, then prednisone 30 mg daily tapered to 10 mg daily at 3 months, or a prednisone-free regimen, consisting of methylprednisolone 500 mg, 250 mg, and 125 mg from days 0 to 2, then no further steroids, tacrolimus 0.075 mg/kg twice a day, and mycophenolate mofetil 1 g twice a day. All patients received thymoglobulin induction 6 mg/kg total dose. Outcome measures were patient and graft survival, BPAR, surgical and wound complications, viral infections and posttransplant diabetes mellitus (PTDM). Both groups had excellent early outcomes with no significant difference in patient or graft survival, early renal function, BPAR, surgical or wound complications, or viral infections between the two groups. Patients in the sirolimus-based CNI-free group had a significantly higher incidence of PTDM and a trend toward more discontinuation due to drug toxicity. Whether either regimen improves long-term outcomes awaits longer follow-up.

Short-term results under three different immunosuppressive regimens at one center.

We examined short-term outcomes and posttransplant medical complications under three different immunosuppressive regimens at a single center. The study design was a randomized, prospective, open-label trial comparing a calcineurin inhibitor-free (CNI) protocol to standard triple therapy with tacrolimus, prednisone, and mycophenolate mofetil. They were also compared to a concurrent but nonrandomized third cohort treated with a prednisone-free protocol. All three groups had excellent early outcomes with no significant difference in patient or graft survival or biopsy-proven acute rejection. Serum creatinine was significantly lower in the CNI-free recipients. Lipid panels and posttransplant diabetes mellitus were significantly lower in the prednisone-free patients. Prednisone-free kidney transplant recipients have improved early glucose metabolism and hyperlipidemia compared to CNI-free or standard triple therapy recipients with comparable rejection and graft survival rates.

ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression.

The interaction between stromal cells and tumor cells is emerging as a critical aspect of tumor progression. Yet there is a paucity of molecular markers for cells participating in such interactions, and only few genes are known to play a critical role in this process. Here, we describe the identification of ADAM12 (a disintegrin and metalloprotease 12) as a novel marker for a subpopulation of stromal cells that are adjacent to epithelial tumor cells in three mouse carcinoma models (models for prostate, breast and colon cancer). Moreover, we show that ADAM12 is essential for tumor development and progression in the W10 mouse model for prostate cancer. These results suggest that ADAM12 might be a useful marker for stromal cells in mouse tumors that are likely to participate in stromal/tumor cell crosstalk, and that ADAM12 is a potential target for design of drugs that prevent carcinoma growth.

Pooling and PCR as a method to combat low frequency gene targeting in mouse embryonic stem cells.

The introduction of germ line modifications by gene targeting in mouse embryonic stem (ES) cells has proven a fundamental technology to relate genes to mammalian biology. Critical aspects required for successful gene targeting have traditionally been experimental enhancements that increase the frequency or detection of homologous recombination within ES cells; however, the utilization of such methods may still result in the failed isolation of a positively targeted ES cell clone. In this study, we discuss the current enhancement methods and describe an ES cell pooling strategy that maximizes the ability to detect properly targeted ES cells regardless of an inherent low targeting efficiency. The sensitivity required to detect correctly targeted events out of a pool of ES cell clones is provided by polymerase chain reaction (PCR), and only those pools containing positives need to be expanded and screened to find individually targeted clones. This method made it possible to identify targeted clones from a screen of approximately 2,300 ES cell colonies by performing only 123 PCR reactions. This technically streamlined approach bypasses the need to troubleshoot and re-engineer an existing targeting construct that is functionally suitable despite its low targeting frequency.

Equitable treatment for HIV/AIDS clinical trial participants: a focus group study of patients, clinician researchers, and administrators in Western Kenya.

OBJECTIVES: To describe the concerns and priorities of key stakeholders in a developing country regarding ethical obligations held by researchers and perceptions of equity or "what is fair" for study participants in an HIV/AIDS clinical drug trial. DESIGN: Qualitative study with focus groups. SETTING: Teaching and referral hospital and rural health centre in Western Kenya. PARTICIPANTS: Potential HIV/AIDS clinical trial participants, clinician researchers, and administrators. RESULTS: Eighty nine individuals participated in a total of 11 focus groups over a four month period. The desire for continued drug therapy, most often life long, following an HIV/AIDS clinical trial was the most common priority expressed in all focus groups. Patients with and without HIV/AIDS also thought subsidizing of drug therapies and education were critical forms of compensation for clinical trial participation. Financial incentives were considered important primarily for purchasing drug therapy as well as obtaining food. Patients noted a concern for the potential mismanagement of any money offered. Clinician researchers and administrators felt strongly that researchers have a moral obligation to participants following a trial to provide continued drug therapy, adverse event monitoring, and primary care. Finally, clinician researchers and administrators stressed the need for thorough informed consent to avoid coercion of study participants. CONCLUSIONS: Kenyan patients, clinician researchers, and administrators believe that it would be unfair to stop antiretroviral therapy following an HIV/AIDS clinical trial and that researchers have a long term obligation to participants.

Quantitative gene expression profiling implicates genes for susceptibility and resistance to alveolar bone loss.

Periodontal disease is one of the most prevalent chronic inflammatory diseases. There is a genetic component to susceptibility and resistance to this disease. Using a mouse model, we investigated the progression of alveolar bone loss by gene expression profiling of susceptible and resistant mouse strains (BALB/cByJ and A/J, respectively). We employed a novel and sensitive quantitative real-time PCR method to compare basal RNA transcription of a 48-gene set in the gingiva and the spleen and the subsequent changes in gene expression due to Porphyromonas gingivalis oral infection. Basal expression of interleukin-1 beta (Il1b) and tumor necrosis factor alpha (Tnf) mRNA was higher in the gingiva of the susceptible BALB/cByJ mice than in the gingiva of resistant A/J mice. Gingival Il1b gene expression increased further and Stat6 gene expression was turned on after P. gingivalis infection in BALB/cByJ mice but not in A/J mice. The basal expression of interleukin-15 (Il15) in the gingiva and the basal expression of p-selectin (Selp) in the spleen were higher in the resistant A/J mice than in the susceptible BALB/cByJ mice. In the resistant A/J mice the expression of no genes detectably changed in the gingiva after infection. These results suggest a molecular phenotype in which discrete sets of differentially expressed genes are associated with genetically determined susceptibility (Il1b, Tnf, and Stat6) or resistance (Il15 and Selp) to alveolar bone loss, providing insight into the genetic etiology of this complex disease.

Alcohol abuse among patients with and without HIV infection attending public clinics in western Kenya.

OBJECTIVE: To evaluate the prevalence of hazardous drinking among persons with and without HIV/AIDS attending both urban/hospital-based and rural clinics in western Kenya. DESIGN: Cross sectional survey. SETTING: The Moi Teaching and Referral Hospital and the Mosoriot rural health care Centre. SUBJECTS: Two hundred and ninety nine adults with and without HIV/AIDS at a teaching and referral hospital and rural health centre. MAIN OUTCOME MEASURES: Results of the World Health Organization's Alcohol Use Disorders Identification Test (AUDIT) where a score of > 8 is indicative of hazardous alcohol consumption. Independent correlates of hazardous drinking were identified using logistic regression analysis including adjustment for common covariables. RESULTS: Study participants were relatively young (38 +/- 9 years) with 55% being male and 54% completing the AUDIT in Kiswahili. Home-made alcohol was more commonly drunk by patients attending the rural health centre while commercial beer was more commonly drunk by patients attending the teaching and referral hospital clinics. Approximately half (54%) of participants reported hazardous drinking behaviour (AUDIT score=9.9 +/- 9.4). Hazardous drinking was most prevalent among men attending the rural health centre (83% hazardous drinkers, AUDIT score=16.0 +/- 9.1). In multivariable analyses adjusting for age, sex and site of care, men remained more than nine times (odds ratio=9.3, 95% C.I.=5.1-16.9) likely to report hazardous drinking behaviour compared to women. CONCLUSIONS: Hazardous drinking is common among patients with and without HIV/ AIDS in western Kenya and is dramatically more common among rural men than women. Effective interventions for HIV/AIDS in this setting must include a concetrated effort to reduce hazardous drinking.

Kidney transplantation in a veterans administration medical center: 40 years' experience.

OBJECTIVES: Advances in immunosuppressive therapy have led to substantial improvements in kidney transplant outcomes in the past 20 years. Kidney transplantation activity started in 1963 at the Veterans Administration Medical Center in Nashville, Tennessee, and continues to grow with increasing numbers of transplants from living-related and unrelated donors. In this study, patient and graft survival rates during 2 different periods were evaluated and compared with non-veterans-administration centers. MATERIALS AND METHODS: Six hundred fourteen kidney transplants were performed between March 1963 and December 2002. For analytic purposes, the 40-year experience was divided into 2 eras based on the immunosuppressive agents used. Azathioprine and prednisone were the immunosuppressive agents used in era 1. A calcineurin-inhibitor-based triple immunosuppressive regimen initially including azathioprine and prednisone and later, mycophenolate mofetil and prednisone, was the preferred immunosuppressive regimen in era 2. RESULTS: In era 1, 1-year patient and graft survival rates were 72.5% and 50%, and 89% and 75% for deceased-donor and living-donor transplants respectively. In era 2, patient survival rates increased to 95.1% and 87.8% for 1 and 3 years respectively, while graft survival increased to 87.6% and 74.9%. Forty-three percent of deceased-donor and 21% of living-donor kidneys were lost owing to rejection in era 1. In era 2, the incidence of acute rejection was 14.5% overall. CONCLUSIONS: Overall, our results are comparable with non-veterans-administration centers and the national average and show that kidney transplantation offers veteran patients with end-stage renal disease a safe and effective treatment with increased quality of life.

Guidelines and algorithms for the use of methylphenidate in children with Attention-Deficit/ Hyperactivity Disorder.

OBJECTIVE: To review published algorithms for guiding the use of methylphenidate (MPH) in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHODS: A consensus roundtable of 12 experts was convened to review the evidence for the safety and efficacy of MPH in the treatment of ADHD, as well as the published algorithms and practice guidelines for using MPH. The experts reviewed the algorithms for practicality and acceptability by clinicians. RESULTS: Algorithms that included MPH commonly selected it as the initial medication to be employed in the treatment of children with ADHD. Factors involved included its high efficacy, good safety record, and the ubiquitous nature of its appearance in the ADHD treatment literature. CONCLUSIONS: MPH should be considered as the first medication to be used in a treatment algorithm for children and adolescents with ADHD.