Brent G. Petty

Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human immunodeficiency virus-infected subjects

We conducted a single-center, double-blind, placebo-controlled phase I study in HIV-positive subjects to ascertain the safety, tolerance, bioavailability, pharmacokinetics, and maximum tolerated dose of HPMPC (cidofovir). Five subjects were randomized to receive drug and two to receive placebo at each of three dosage tier (1, 3, and 10 mg/kg) with a 2-week washout period doses. Subjects at 1 and 3 mg/kg received single doses of HPMPC by subcutaneous (s.c.) intravenous (i.v.), and oral (p.o.) routes, while subjects at 10 mg/kg received only i.v. and p.o. doses. For subjects already taking zidovudine, zidovudine AUC values are determined before and then with HPMPC administration for each route. The AUC values of HPMPC were dose-proportional. Subcutaneous bioavailability was essentially equivalent to that of the intravenous route, but the development of transient local fibrosis ad the volumes needed for subcutaneous dosing precluded higher subcutaneous dosing than 3 mg/kg. Oral bioavailability was poor, estimated to be less than 5%. Drug elimination was predominantly renal. Nephrotoxicity in one subject was the only serious adverse event observed. This subject had a significant lag period prior to oral absorption and also had the highest AUC values for both HPMPC and zidovudine. We found no consistent effect on zidovudine AUC concomitant HPMPC.

Perioperative medication management

One of the consultants roles is to make recommendations regarding the use of medications in the perioperative period. Unfortunately, the data in this area are often insufficient to provide evidence-based recommendations. In this article, we have provided advice considering the pharmacokinetics of the drug, the effect on the primary disease of stopping medications, and the effect of the medication on perioperative risk, including potential drug interactions with anesthetic agents.

Hemophilus aphrophilus meningitis followed by vertebral osteomyelitis and suppurative psoas abscess

Hemophilus aphrophilus is an uncommon pathogen in man. It has rarely been reported as a cause of meningitis, exclusively in boys three years or younger. Osteomyelitis due to this organism is also rare. H. aphrophilus was responsible for meningitis, probable thoracic empyema, and ultimately vertebral osteomyelitis and suppurative psoas abscess formation in a woman following metrizamide myelography. The patient responded well to antibiotic treatment and surgical drainage. The organism was sensitive not only to chloramphenicol but also to newer cephalosporin antibiotics.

A study of potential vestibulotoxic effects of once daily versus thrice daily administration of tobramycin

Tobramycin 5.1 mg/kg/day was administered for 9 days to 20 healthy human volunteers to determine the potential vestibulotoxicity of once daily versus thrice daily treatment regimens. Vestibular function was tested carefully before, during, and following drug administration, using a battery of postural and caloric tests.

Provider-to-Provider Communication during Transitions of Care from Outpatient to Acute Care: A Systematic Review

ABSTRACTBACKGROUNDMost research on transitions of care has focused on the transition from acute to outpatient care. Little is known about the transition from outpatient to acute care. We conducted a systematic review of the literature on the transition from outpatient to acute care, focusing on provider-to-provider communication and its impact on quality of care.METHODSWe searched the MEDLINE, CINAHL, Scopus, EMBASE, and Cochrane databases for English-language articles describing direct communication between outpatient providers and acute care providers around patients presenting to the emergency department or admitted to the hospital. We conducted double, independent review of titles, abstracts, and full text articles. Conflicts were resolved by consensus. Included articles were abstracted using standardized forms. We maintained search results via Refworks (ProQuest, Bethesda, MD). Risk of bias was assessed using a modified version of the Downs’ and Black’s tool.RESULTSOf 4009 citations, twenty articles evaluated direct provider-to-provider communication around the outpatient to acute care transition. Most studies were cross-sectional (65 %), conducted in the US (55 %), and studied communication between primary care and inpatient providers (62 %). Of three studies reporting on the association between communication and 30-day readmissions, none found a significant association; of these studies, only one reported a measure of association (adjusted OR for communication vs. no communication, 1.08; 95 % CI 0.92–1.26).DISCUSSIONThe literature on provider-to-provider communication at the transition from outpatient to acute care is sparse and heterogeneous. Given the known importance of communication for other transitions of care, future studies are needed on provider-to-provider communication during this transition. Studies evaluating ideal methods for communication to reduce medical errors, utilization, and optimize patient satisfaction at this transition are especially needed.

Metabolism of Desciclovir, a Prodrug of Acyclovir, in Humans After Multiple Oral Dosing

Desciclovir (DCV), a prodrug of the antiherpetic agent acyclovir (ACV), is converted in humans to ACV, presumably by xanthine oxidase. Further metabolism of these two compounds was investigated in six human volunteers given 250 mg DCV orally every eight hours for ten days plus one dose on day 11. The mean percent dose recovered in urine (24 hr) on days 2, 5, and 10 as carboxy‐DCV (2%) and as carboxy‐ACV (14%) along with recoveries of DCV (6%) and ACV (62%) gave a mean total of 84% cleared over a 24‐hour period at steady state. Carboxyl metabolites were not found in the plasma of these same subjects at peak DCV concentration on dose day 11. The ratios of DCV and ACV to their corresponding carboxyl metabolites in urine were 4:1 and 3:1, respectively, suggesting that there is little or no difference in the efficiency of these two substrates for oxidation to their carboxylic acid metabolites.

Pharmacodynamics and tolerance of oral sustained release ritodrine

A new oral sustained release formulation of ritodrine was tested for patient tolerance in this open study. The doses tested were 120 mg/day, 240 mg/day, and 360 mg/day. No objective toxicity was seen at any level. Doses of 120 mg/day and 240 mg/day were well-tolerated. Of the subjects who received the 360 mg/day dose, most tolerated it well.

Increasing Advance Care Planning Completion at an Academic Internal Medicine Outpatient Clinic

BACKGROUND We sought to increase advance care planning (ACP) completion at an academic internal medicine clinic through an electronic health record. MEASURES Number of eligible patients who completed a form of ACP. INTERVENTION Multidisciplinary team approach with engagement from providers and clinic staff; implemented informational letter and appropriate forms to eligible patients before appointment; informational video and provider reminders at time of appointment. OUTCOMES Of 480 eligible patients, 327 (68%) completed one or more forms of ACP or had a discussion with their provider. Discussed but not completed was highest (53%). The three types of ACP completed were 1) a state-formatted advance directive form (47%), 2) Medical Orders for Life-Sustaining Treatment (45%), and 3) power of attorney designation (8%). CONCLUSIONS Implementation of a multi-disciplinary approach can facilitate ACP. However, challenges still arise because in more than half of the cases, advance care efforts led only to a discussion.

Making General Internal Medicine Research Relevant to the Older Patient with Multiple Chronic Comorbidities

ABSTRACTGeneral Internal Medicine research evolves in response to the needs of the patients to whom we provide care. Currently, many studies exclude older adults who deeply affect the clinical care of this population. With the number of older adults increasing, creating research protocols that include older adults with multiple chronic comorbidities is imperative. Through funding from the Association of Specialty Physicians, a working group of aging-responsive researchers from the Society of General Internal Medicine was convened to tackle this issue. The goal of this article is threefold: 1) to shed light on the current exclusion of older adults in research; 2) to identify and propose research protocol solutions for overcoming barriers to including older adults in research; and 3) to provide suggestions for research funding. The extent to which these recommendations can create change depends greatly on our researcher colleagues. By embracing these challenges, we hope that the care provided to older adults with multiple chronic conditions will no longer be extrapolated, but become evidence-based.

The effect of increasing gastric pH upon the bioavailability of orally-administered foscarnet

For systemic use, the anti-cytomegalovirus (CMV) agent foscarnet must be given intravenously because oral administration results in unmeasurable or barely measurable plasma levels. At low pH, foscarnet decomposes via an acid-catalyzed decarboxylation; therefore, poor oral bioavailability might be due to decomposition of foscarnet in gastric acid. We evaluated whether increasing gastric pH with ranitidine would enhance the absorption of oral foscarnet in six asymptomatic HIV-infected individuals. Each volunteer received two oral 4000-mg (60 mg/kg) doses of foscarnet, preceded intravenously by a 20-min infusion of either ranitidine 50 mg in D5W or D5W alone in a randomized, double-blind, cross-over study. Intragastric pH monitoring revealed that subjects had evidence of gastric acid production (pH < 2.0) prior to administration of ranitidine and increased gastric pH (pH > 6.0) following ranitidine administration. Most foscarnet plasma levels were below the assay limit of detection (33 microM) with only 4/30 levels detectable after D5W and 8/30 after ranitidine. Urinary recovery of foscarnet increased after ranitidine pretreatment. A mean recovery of 9.9% of the drug was realized in the urine in 24 h following ranitidine pretreatment compared to 6.2% of the dose after D5W pretreatment (P < 0.03). We estimate that 9.9% recovery in the urine in 24 h is equivalent to absorption of 17.1% of the oral dose. In spite of the enhanced bioavailability associated with ranitidine pretreatment, the degree of absorption is still insufficient to achieve effective plasma concentrations for the treatment of CMV or acyclovir-resistant herpes viruses. We conclude that gastric acidity is a determinant of foscarnet absorption, albeit not a major one. Oral foscarnet is unlikely to be clinically useful even if administered in the setting of increased gastric pH.