Drug Toxicity Monitoring Research Articles

HIV Quality of Care Assessment at an Academic Hospital

Rapid changes in HIV treatment guidelines and antiretroviral therapy drug safety data add to the increasing complexity of caring for HIV-infected patients and amplify the need for continuous quality monitoring. The authors created an electronic HIV database of 642 patients who received care in the infectious disease (ID) and general medicine clinics in their academic center to monitor HIV clinical performance indicators. The main outcome measures of the study include process measures, including a description of how the database was constructed, and clinical outcomes, including HIV-specific quality improvement (QI) measures and primary care (PC) measures. Performance on HIV-specific QI measures was very high, but drug toxicity monitoring and PC-specific QI performance were deficient, particularly among ID specialists. Establishment of HIV QI data benchmarks as well as standards for how data will be measured and collected are needed and are the logical counterpart to treatment guidelines.

Global HIV/AIDS Clinical and Translational Pharmacology

Global HIV/AIDS Clinical and Translational Pharmacology

Abstract P331: Metabolic Dynamics and Phosphometabolomic Fingerprinting Using 18 O-Assisted 31 P NMR and Mass Spectrometry

Evaluation of disease phenotypes and drug effects requires knowledge not only metabolite levels but also their turnover rates from which metabolic fluxes and status of the whole energetic system can be determined. Oxygen-18-assited 31 P NMR and mass spectrometric technique uniquely allow simultaneous measurements of phosphorus-containing metabolite levels and their turnover rates. This includes simultaneous recordings of 18 O-labeling rates reflecting ATP synthesis (γ-ATP) and ATP utilization (Pi), phosphotransfer fluxes through adenylate kinase (β-ATP/ADP), creatine kinase (CrP) and glycolytic pathways (G-6-P) as well as Krebs cycle associated mitochondrial nucleotide turnover (γ/β-GTP), substrate shuttle (G-3-P) and glycogen metabolism (G-1-P). Metabolomic and fluxomic profiling of hearts and body fluids of phosphotransfer enzyme deficient transgenic animals using 18 O-assisted GC/MS, 1 H and 18 O-assisted 31 P NMR indicate selective metabolic perturbations and adaptations in the whole energetic system. Adenylate kinase and creatine kinase deficiencies were associated with altered metabolomic profiles, increased mitochondrial capacities and redistribution of phosphotransfer flux through glycolytic and guanine nucleotide systems. These phosphometabolomic alterations were more expressed when animals were subjected to treadmill exercise, mitochondria-targeting drugs such as metformin and high-fat diet. Metabolite turnover rates are correlated with heart performance unveiling robustness and dynamics rearrangements in cell bioenergetics infrastructure. Glycerophosphate, G-3-P, metabolic dynamics is altered in transgenic animal models indicating defects in substrate shuttle and supply of reducing equivalents to mitochondria. This is of importance since G-3-P metabolic abnormalities and metabolic arrest are linked to human diseases such as sudden death syndrome. Thus, our study demonstrates that phosphometabolomic and fluxomic profiling is a valuable tool for metabolic phenotyping of transgenic animal models of human diseases as well as for plasma biomarker identification and monitoring of treatment efficacy and drug toxicity.

Accurate CD4 T-cell enumeration and antiretroviral drug toxicity monitoring in primary healthcare clinics using point-of-care testing

To evaluate the accuracy of point-of-care tests (POCTs) for CD4 cell, clinical chemistry and hemoglobin in primary healthcare clinics in Mozambique. POCT and laboratory-based assays were conducted on adult HIV-positive patients enrolled consecutively at primary healthcare clinics in Mozambique. Patients were tested on-site with POCT CD4 (Pima), clinical chemistry (Reflotron) and hemoglobin (HemoCue) devices using finger prick blood. Results obtained on paired blood samples were used for agreement analysis (bias and limits of agreement). Repeatability analysis was also performed for POCT CD4 cell counting. Primary health nurses operating the Pima, Reflotron and HemoCue POCT devices produced results with low levels of bias for CD4(+) T-cell counts (-52.8 cells/μl), alanine aminotransferase (-0.2 U/l), aspartate aminotransferase (-4.0 U/l) and hemoglobin (0.95 g/dl). CD4(+) T-cell counts in paired specimens of finger prick and venous blood tested on the POCT CD4 device were in close agreement (bias -9 cells/μl, coefficient of variation 10.6%). The repeatability of POCT CD4 cell counting was similar to that observed with laboratory instruments (bias -6.2 cells/μl, coefficient of variation 10.7% vs. bias -5.7 cells/μl, coefficient of variation 7.5%). Primary health clinic nurses generated accurate results for CD4(+) T-cell counts, liver enzymes and hemoglobin using simple POC devices on finger prick samples at decentralized antiretroviral therapy (ART) clinics. POC diagnostics to monitor ART at primary healthcare level is technically feasible and should be utilized in efforts to decentralize HIV care and treatment.

Drug Monitoring in Systemic Lupus Erythematosus: A Systematic Review

To conduct an evidence-based review of the common medication toxicities and strategies and utility of drug toxicity monitoring among patients with systemic lupus erythematosus (SLE). PubMed and other databases were searched for articles published between the years 1960 and 2010 for keywords referring to medication toxicity or monitoring strategies for 7 drugs commonly used in SLE. All relevant English-language articles were reviewed. Most of the evidence we reviewed comprised studies that addressed the incidence of toxicity-randomized trials that compare different monitoring strategies for these drugs do not exist. Data to describe the frequency of adverse events and appropriate strategies for screening for these events are scarce. Toxicities do not appear to be substantially more common among patients with SLE compared to other conditions for which these drugs are used. Our review demonstrates that the scientific basis for many aspects of drug toxicity monitoring is weak and that most current recommendations are based largely on expert consensus. We present a future research agenda to address these gaps.

Breast Cancer Prevention Trials: Large and Small Trials

Breast cancer is the most common cancer among women in the United States, with 192,870 new cases and 40,170 deaths due to this disease estimated to have occurred 2009. An emphasis on prevention has been increasing in view of a persisting high incidence of disease. Seventy percent of breast cancers are estrogen receptor (ER)-positive, and are therefore presumed to be hormone-responsive and potentially treatable or preventable by anti-estrogenic agents. To date, the large, phase III randomized controlled breast cancer prevention trials have tested and are testing only hormonal drugs designed to antagonize the carcinogenic effect of endogenous estrogen; these agents are either selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). The SERMs, tamoxifen and raloxifene, have been shown in these large trials to reduce the risk of ER-positive breast cancers; prevention trials of AIs are ongoing. Interest is now focusing on developing agents with a broader spectrum of preventive activity, particularly with regard to ER-negative subtypes of breast cancer. A number of phase I and II trials using tissue-derived surrogate endpoint biomarkers (SEBs) as outcomes have been implemented. These smaller trials address prevention not only of ER-negative but also ER-positive breast cancers, since approximately 50% of the latter have been shown to be resistant to the estrogen-targeting drugs used in the large trials. Issues of importance in these smaller trials include choice of agent, selection of appropriate trial participants, trial design, method of access to breast tissue in women without cancer, selection and monitoring of SEBs, and monitoring of drug toxicity.

Immunologic rheumatic disorders

We provide the basics for clinicians who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases (ie, RA, seronegative spondyloarthropathy, SLE, antiphospholipid syndrome, Sjögren syndrome, scleroderma, and polymyositis/dermatomyositis) will be covered. In the past decade, treatment for RA and seronegative spondyloarthropathy has substantially improved. Their treatment has been revolutionized by the use of methotrexate and, more recently, TNF inhibitors, T-cell costimulation modulators, and B-cell depletion. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome, SLE, or scleroderma can be identified and then blocked, as in the example of TNF inhibitors in patients with RA, more specific treatments will become available. Thus RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed.

Adjuvant Interferon Therapy for Patients with Uveal Melanoma at High Risk of Metastasis

To examine whether interferon (IFN)-alfa-2a treatment after radiation or enucleation reduces death rates in patients with uveal melanoma. Interventional, comparative case series. Subjects were identified through the ocular oncology clinic of the Massachusetts Eye and Ear Infirmary. Patients eligible for the study were at increased risk of metastasis because of the presence of at least one of the following characteristics: age >or=65 years, largest tumor diameter (LTD) >or=15 mm, ciliary body involvement of the tumor, or extrascleral tumor extension. Between May 1995 and June 1999, 121 patients with choroidal or ciliary body melanoma began a 2-year course of therapy (3 MIU IFN-alfa-2a subcutaneously 3 times per week), initiated within 3 years of primary therapy. All patients underwent regular monitoring for drug toxicity. To evaluate IFN-alfa-2a efficacy, we selected a series of historical controls frequency-matched (2:1) to IFN-alfa-2a-treated patients on age (+/-5 years), LTD (+/-3 mm), gender, and survival time between primary therapy and initiation of IFN therapy. Survival status was ascertained for all patients through December 2006. Melanoma-related mortality, metastasis, IFN-related toxicities. Fifty-five patients (45%) completed therapy; the median dose for IFN-alfa-2a-treated patients was 792 MIU (85% of the theoretic dose). The median follow-up time in the IFN-alfa-2a-treated group was approximately 9 years. Treatment and control groups were similar with respect to age (P = 0.78), LTD (P = 0.38), and gender (P = 1.0). Of 363 patients, 108 developed metastasis under observation; 42 of these were IFN-alfa-2a-treated patients. Cumulative 5-year melanoma-related death rates were 17% in the radiation or enucleation-only group, 15% in those who completed the entire IFN-alfa-2a course, and 35% in those who discontinued IFN-alfa-2a therapy. In multivariate Cox regression, IFN-alfa-2a had no significant influence on melanoma-related mortality (rate ratio = 1.02, 95% confidence interval, 0.68-1.5, P = 0.91) or all-cause mortality (rate ratio = 0.84, 95% confidence interval, 0.58-1.2, P = 0.34). Interferon-alfa-2a has no material influence on survival in patients with choroidal melanoma.

A quality indicator set for systemic lupus erythematosus

To systematically develop a quality indicator (QI) set for systemic lupus erythematosus (SLE). We used a validated process that combined available scientific evidence and expert consensus to develop a QI set for SLE. We extracted 20 candidate indicators from a systematic literature review of clinical practice guidelines pertaining to SLE. An advisory panel revised and augmented these candidate indicators and, through 2 rounds of voting, arrived at 25 QIs. These QIs advanced to the next phase of the project, in which we employed a modification of the RAND/UCLA Appropriateness Method. A systematic review of the literature was performed for each QI, linking the proposed process of care to potential improved health outcomes. After reviewing this scientific evidence, a second interdisciplinary expert panel convened to discuss the evidence and provide final ratings on the validity and feasibility of each QI. The final expert panel rated 20 QIs as both valid and feasible. Areas covered included diagnosis, general preventive strategies (e.g., vaccinations, sun avoidance counseling, and screening for cardiovascular disease), osteoporosis prevention and treatment, drug toxicity monitoring, renal disease, and reproductive health. We employed a rigorous multistep approach with systematic literature reviews and 2 expert panels to develop QIs for SLE. This new set of indicators provides an opportunity to assess health care quality in patients with SLE and represents an initial step toward the important goal of improving care in this patient population.

Pharmacovigilance in Herbal Medicine: A Paradigm to Drug Toxicity Monitoring in Conventional Health Care

From prehistoric times, herbal medicine has been used by various communities and civilizations throughout the world. This trend continues to the present day. For the past several decades, herbal medicines have been increasingly consumed by people without prescription. They are traditionally considered as harmless since they belong to natural sources. Herbal formulations which have reached widespread acceptability as therapeutic agents are such as antidiabetics, anti-arthritics, aphrodisiacs, hepatoprotectives, cough remedies, memory enhancers and adoptogens. However, with a more efficient case reporting of adverse drug reactions, the hazards of herbal medicines as self prescriptions have been well recorded. In this regard the World Health Organization (WHO) has set specific guidelines for the assessment of the safety, efficacy and quality of herbal medicines. The purpose of pharmacovigilance is to detect, assess and understand, and to prevent the adverse effects or any other possible drug-related problems, which is not only confined to chemical drugs, but extended to herbal, traditional and complementary medicines, biologicals, vaccines, blood products and medical devices. Herbal pharmacovigilance should be implemented and authorities should record apart from existing information on various aspects of the single herb and/or compound herbal formulations on concomitant use with chemical drugs, adverse drug reaction, delayed or acute toxic effects, allergies etc. Most over-the-counter herbal products like ginseng have drawn great public attention but there are several case reports mentioned in the literature of adverse drug reactions of herbal drugs which are generally considered safe. In this paper, we have succinctly reviewed the various aspects associated with the pharmacovigilance of herbal medicines ranging from the pathophysiology to the various clinical elements of adverse drug reactions associated with herbal medicine.

Outpatient assessment of systemic vasculitis

The vasculitides are complex, multisystem diseases, the natural history of which has been transformed by the use of immunosuppressive therapy. In many cases, survival is characterized by the presence of ongoing low-grade disease activity and, now that patients can survive acute, life-threatening manifestations of vasculitis, the new challenge is to provide accurate descriptions of these problems so as to plan appropriate changes in therapy to ensure optimal control of disease, with minimal toxicity, damage, and impairment of function. To achieve these aims, it is necessary to undertake structured evaluation of patients, with a significant dependence on careful clinical observation, supported by appropriate laboratory investigation at all stages from diagnosis to long-term care of these patients. This chapter reviews the important aspects of disease assessment and recommends a strategy for managing these complex patients. We can make use of standardized disease assessment instruments, such as the Birmingham Vasculitis Assessment Score and the Vasculitis Damage Index, to serve as an aide memoire in documenting the clinical features of disease. Routine monitoring for drug toxicity in the short-term and long-term is essential. Above all, however, it is very important to review these patients regularly and see them urgently in case of flares or complications, which are a common problem in most forms of vasculitis.

Therapeutic drug and cardiovascular disease risk monitoring in patients with bipolar disorder

Objectives We assessed whether patients with bipolar disorder received serum drug level and toxicity monitoring for mood stabilizers and assessment of cardiovascular disease (CVD)-related risk factors attributed to atypical antipsychotic medications. Methods A population-based study of individuals with bipolar disorder was conducted between July 2004 and July 2006. Based on American Psychiatric and American Diabetes Association guidelines, we assessed whether patients received recommended drug level and toxicity monitoring tests on or within 6 months for mood stabilizers, and lipid and glucose tests for atypical antipsychotics. Multivariable regression was used to determine the patient factors associated with receipt of lab tests. Results Of the 435 patients (mean age = 49 years, 14.3% female, 22.8% nonwhite), 60.3% were currently prescribed mood stabilizers and 65.5% were prescribed atypical antipsychotics. Overall, 39.7% received a serum drug level for mood stabilizers, 38.8% received a thyroid function test for lithium, and the majority (71.4%–75.9%) received complete blood counts and hepatic function tests for valproate or carbamazepine. About half of patients prescribed atypical antipsychotics received cholesterol counts (49.6%), and 68.7% received serum glucose levels. After adjusting for patient factors, women prescribed atypical antipsychotics were less likely than men to receive cholesterol counts (OR = 0.43; p < 0.05). Limitations Single-site retrospective study and a relatively short observation period. Conclusions About half of patients received recommended lab tests for mood stabilizers and atypical antipsychotics. Additional research regarding whether the receipt of these lab tests is associated with improved outcomes will inform efforts to improve quality of care related to drug toxicities and CVD risk factors in patients with bipolar disorder.

Pharmaco-EEG in Psychiatry

In spite of its origins deeply rooted in the discipline, pharmaco-EEG applications in psychiatry remain limited to its achievements in the field of psychotropic drugs classification and, in few instances, discovery. In the present paper two attempts to transfer pharmaco-EEG methods to psychiatric clinical routine will be described: 1) monitoring of psychotropic drug toxicity at the central nervous system level, and 2) prediction of clinical response to treatment with psychotropic drugs. Both applications have been the object of several investigations providing promising and sometimes consistent findings which, however, had no impact on clinical practice. For the first topic, the review is limited to antipsychotics, lithium and recreational drugs, as for other psychotropic drugs mostly case studies are available, while for the response prediction it will include antipsychotics, antidepressants, anxiolytics, psychostimulants and nootropics. In spite of several methodological limitations, pharmaco-EEG studies dealing with monitoring of antipsychotic- and lithium-induced EEG abnormalities went close to, but never became, a clinical routine. EEG studies of recreational drugs are flawed by several limitations, and failed, so far, to identify reliable indices of CNS toxicity to be used in clinical settings. Several QEEG studies on early predictors of treatment response to first generation antipsychotics have produced consistent findings, but had no clinical impact. For other psychotropic drug classes few and inconsistent reports have appeared. Pharmaco-EEG had the potential for important clinical applications, but so far none of them entered clinical routine. The ability to upgrade theories and methods and promote large scale studies represent the future challenge.

Proposed recommendations for the management of HIV post-exposure prophylaxis after sexual, injecting drug or other exposures in Europe.

Post-exposure prophylaxis (PEP) is the standard of care for a healthcare worker (HCW) accidentally exposed to an HIV infected source person (occupational exposure), but this is not the case for non-occupational exposures. Very few national guidelines exist for the management of non-occupational exposures to HIV in Europe, contrarily to the occupational ones. The administration of non-occupational post-exposure prophylaxis (NONOPEP) for HIV may be justified by: a biological plausibility, the effectiveness of PEP in animal studies and occupational exposures in humans, efficacy in the prevention of mother to child HIV transmission, and cost effectiveness studies. These evidences, the similar risk of HIV transmission for certain non-occupational exposures to occupational ones, and the conflicting information about attitudes and practices among physicians on NONOPEP led to the proposal of these European recommendations. Participant members of the European project on HIV NONOPEP, funded by the European Commission, and acknowledged as experts in bloodborne pathogen transmission and prevention, met from December 2000 to December 2002 at three formal meetings and a two day workshop for a literature review on risk exposure assessment and the development of the European recommendations for the management of HIV NONOPEP. NONOPEP is recommended in unprotected receptive anal sex and needle or syringe exchange when the source person is known as HIV positive or from a population group with high HIV prevalence. Any combination of drugs available for HIV infected patients can be used as PEP and the simplest and least toxic regimens are to be preferred. PEP should be given within 72 hours from the time of exposure, starting as early as possible and lasting four weeks. All patients should receive medical evaluation including HIV antibody tests, drug toxicity monitoring and counseling periodically for at least 6 months after the exposure. NONOPEP seems to be a both feasible and frequent clinical practice in Europe. Recommendations for its management have been achieved by consensus, but some remain controversial, and they should be updated periodically. NONOPEP should never be considered as a primary prevention strategy and the final decision for prescription must be made on the basis of the patient-physician relationship. Finally, a surveillance system for these cases will be useful to monitor NONOPEP practices in Europe.

Surgical management and outcome of tuberculous atlantoaxial dislocation: a 15-year experience.

Tuberculous atlantoaxial dislocation is a rare disease entity. However, tuberculosis continues to be endemic in developing countries. Its earliest clinical presentation may be nonspecific, and delay in diagnosis may lead to irreversible neurological deficit. The management of tuberculous atlantoaxial dislocation includes ventral cervicomedullary decompression, occipitocervical arthrodesis, and administration of antituberculous medications. Eighteen patients with tuberculous atlantoaxial dislocation who presented with neck pain and/or occipital headache, restriction of neck movement, difficulty swallowing, and signs of myelopathy were studied. Four patients had evidence of associated pulmonary tuberculosis. Plain x-rays of the cervical spine, computed tomographic scans, and magnetic resonance images were obtained in all patients for diagnosis and to assess the degree of dislocation and cervicomedullary compression. Simultaneous anterior neural decompression, via a transcervical retropharyngeal approach, and posterior arthrodesis were performed on all patients while they remained under anesthesia. Antituberculous chemotherapy was continued for 18 months. Histopathological analysis of excised tissue was consistent with tuberculosis in all patients. However, Ziehl-Neelsen staining for acid-fast bacilli was positive in two cases, and culture for Mycobacterium tuberculosis was negative in all patients. Patients with severe myelopathy experienced marked improvement. One patient died of fulminant resistant tuberculous meningitis. The transcervical retropharyngeal approach to the craniovertebral junction provides direct access to the lesion and avoids the potential bacterial contamination of the oral and pharyngeal cavity. It also prevents the development of persistent fistulae. Posterior stabilization should be performed directly after anterior neural decompression, while the patient remains under anesthesia, to prevent neurological deterioration before subsequent posterior fixation. This technique also is helpful for early mobilization of patients. The aim of surgical treatment should be to obtain biopsy tissue and to perform radical excision of epidural granulation tissue/abscess and infected bone using microsurgical technique. Antituberculous medication must be continued for 18 months with four drug regimens, and continuous monitoring of drug toxicity should be performed throughout the course of treatment.

Concepts in design of comparative clinical trials of antifungal therapy in neutropenic patients

Fundamental to the successful implementation of antifungal compounds in neutropenic patients is the appropriate design of comparative clinical trials investigating their safety and efficacy. The key elements of comparative clinical trial design include issues of enrolment, stratification, randomization, blinding, administration of study drugs, monitoring of drug toxicity, definitions, and key statistical elements of end points, sample size, and tools for data analysis. The initial selection of compounds and the timing of initiation of antifungal therapy in comparative clinical trials are predicated to a large degree on the in vitro and in vivo activities, plasma pharmacokinetics, profiles of safety and toxicity of the study drugs. Phase I and II studies have a critical role in designing comparative clinical trials of antifungal therapy by providing data on safety, tolerance, and plasma pharmacokinetics of the investigational agent. As new antifungal agents are developed in response to the challenge of invasive fungal infections in immunocompromised patients with cancer, thoughtfully designed and carefully implemented clinical trials will be essential in determining the future utility of these promising compounds.

Rapid protein display profiling of cancer progression directly from human tissue using a protein biochip

The complicated, changing pattern of protein expression should contain important information about the pathologic process taking place in the cells of actual tissue. Utilization of this information for the selection of druggable targets could be possible if a means existed to rapidly analyze and display changes in protein expression in defined microscopic cellular subpopulations. As a demonstration of feasibility, we show the generation of sensitive, rapid, and reproducible molecular weight protein profiles of patient-matched normal, premalignant, malignant, and metastatic microdissected cell populations from stained human esophageal, prostate, breast, ovary, colon, and hepatic tissue sections through the application of an affinity-based biochip. Reproducible, discriminatory protein biomarker profiles can be obtained from as few as 25 cells in less than 5 min from dissection to the generation of the protein fingerprint. Furthermore, these protein pattern profiles reveal reproducible changes in expression as cells undergo malignant transformation, and are discriminatory for different tumor types. Consistent protein changes were identified in the microdissected cells from patient-matched tumor and normal epithelium from eight out of eight different malignant esophageal tissue sets and three out of three malignant prostate tissue sets. A means to rapidly generate a display of expressed proteins from microscopic cellular populations sampled from tissue could be an important enabling technology for pharmacoproteomics, molecular pathology, drug intervention strategies, therapeutic assessment of drug entities, disease diagnosis, toxicity, and gene therapy monitoring. Drug Dev. Res. 49:34–42, 2000. Published 2000 Wiley-Liss, Inc.

Maximizing the benefit of pharmacotherapy in Parkinson's disease.

Levodopa is one of the principal agents administered to treat patients with Parkinson's disease (PD). Several pharmacologic strategies can limit its side effects and enhance its activity. Although certain exceptions apply, dosage adjustments and drug changes should be instituted slowly. Levodopa is typically introduced in the form of carbidopa-levodopa, with upward dosage titration weekly until symptoms improve. A dopamine agonist may be added when the dosage of levodopa reaches 300-500 mg/day Dopamine agonists are used to control symptoms of PD, decrease or delay motor fluctuations, and allow lower dosages of levodopa to be administered. These agents are also being prescribed early in treatment before carbidopa-levodopa therapy is begun. Addition of a catechol-O-methyltransferase inhibitor can increase the duration of levodopa's effect and may prove especially valuable for patients who experience early wearing off of levodopa. Patients with PD require close monitoring for drug toxicity. Because most of them are treated with several agents to provide maximum improvement and also receive treatment for comorbid conditions, drug-drug interactions are possible. Frequently, clinically significant interactions are associated with agents that block D2 receptors or deplete dopamine stores in the brain.

Postexposure prophylaxis for human immunodeficiency virus at San Francisco General Hospital

S an Francisco General Hospital (SFGH) is a center of excellence for the care of human immunodeficiency virus (HIV)-infected patients. For the past decade, the proportion of patients with HIV on the adult medical and surgical services has been 2535%. In addition, >2,500 patient visits for HIV care occur each month in the out-patient clinics. The high prevalence of HIV in this institution and the corresponding high risk of occupational exposure was recognized very early on in the AIDS epidemic and motivated the development of a comprehensive plan for coordinating occupational HIV exposure prevention and postexposure care. The components of the plan are developed and implemented by a multidisciplinary team, the Occupational Infectious Diseases Program (OIDP).‘,’ The specific protocols we use for treatment, follow-up, and drug toxicity monitoring are available on our website: http://epi-center.ucsf.edu. At SFGH, the exposure management program is designed to be generic and to accommodate all potential exposures to bloodborne pathogens.’ The first component is exposure prevention, the highest priority for exposure management. The prevention program includes (1) policy development and implementation, procedure reviews, and staff training; (2) exposure surveillance; and (3) targeted prevention interventions (including safety devices and sharpsdisposal programs). The second program component is individual postexposure care (the focus of this review), including (1) facilitated exposure event reporting; (2) wound care and prophylactic treatment; (3) diagnostic monitoring and follow-up; and (4) counseling and support. A simple three-step paradigm is used to instruct workers about postexposure interventions at SFGH (Table I). The Needlestick Hotline is designed to facilitate access to expertise for all occupational exposures. Expert counseling and advice as well as quick triage to prophylaxis for HIV and hepatitis B virus (HBV) exposures are provided 24 hours a day,

Flow Injection Proton Nuclear Magnetic Resonance Spectroscopy Combined With Pattern Recognition Methods: Implications for Rapid Structural Studies and High Throughput Biochemical Screening

The applicability of novel NMR flow probe technology has been tested by the measurement of 300 MHz 1H NMR spectra of a series of rat urine samples. Compared with conventional automatic operation, the method resulted in a significantly increased rate of sample throughput, required minimal spectrometer optimisation before each measurement and avoided the need for expensive and fragile NMR sample tubes. The NMR approach has been coupled with computer methods for spectral data reduction and classification using, in this case, principal components analysis. The flow probe NMR approach offers distinct advantages in situations where large numbers of samples require NMR analysis in a short period of time. These could include routine samples from high throughput chemical synthesis, biofluid samples for drug toxicity monitoring as shown here, samples for clinical diagnosis or real-time analysis in chemical production facilities.