Annals of Pharmacotherapy

To review the risk of HIV infection following occupational exposure, the theoretical basis for chemoprophylaxis, investigative experience with chemoprophylaxis in animals and humans, and the economic aspects of postexposure chemoprophylaxis.

English-language articles and conference proceedings pertaining to the risk of occupational HIV infection and to postexposure chemoprophylaxis.

Studies evaluating chemoprophylaxis of HIV infection following occupational exposure were selected for review. Abstracts reporting ongoing clinical trials were also included.

In vitro studies are discussed to provide the immunologic rationale for chemoprophylaxis. Animal studies examining the efficacy of chemoprophylaxis in preventing non-HIV retroviral infection are reviewed, and their applicability to human HIV infection is critically evaluated. Human studies and case reports describing attempts at chemoprophylaxis of HIV infection following occupational exposure are discussed.

Chemoprophylaxis of HIV infection following occupational exposure has focused on the use of zidovudine (ZDV) because it was previously the only antiretroviral agent approved for treating HIV infection. Animal models of retroviral infection provide conflicting data regarding the efficacy of ZDV chemoprophylaxis, and there are important questions about the applicability of animal data to human HIV infection because of differences in natural histories of non-HIV retroviral infections, inoculum size, dosing of ZDV, and routes of infection. Human surveillance studies are thus far inadequate to determine the efficacy of ZDV prophylaxis because of the very low HIV seroconversion rates following occupational exposure. ZDV is well tolerated during short-term administration in people without HIV infection, but long-term safety is unknown. In addition, the true cost-benefit ratio of ZDV chemoprophylaxis is uncertain.

Current data from in vitro, animal, and human studies are inadequate to define the appropriate role of ZDV in preventing HIV infection following occupational exposure. Limited toxicity data and the high cost of treatment must be weighed against the theoretical benefits of ZDV use in this setting. The decision to employ ZDV for postexposure prophylaxis must ultimately be based on existing institutional policies, the attitude of the responsible physician regarding such practice, and/or the desires of the exposed healthcare worker after being properly informed of potential risks and benefits.

To ascertain the clinical accuracy of equations that estimate creatinine clearance to predict the correct drug doses in hospitalized elderly patients

Single 24-hour creatinine clearance measurement compared with estimated creatinine clearances derived from eight equations using total and modified ideal body weight

Nonintensive care medical and surgical units at a county hospital

15 patients with urethral catheters were enrolled in each of three age groups: 65–75, 76–85, and ≥86 years

Drug–dose predictions, bias, precision, and absolute errors

The bias for all equations was −4.0−42.0 mL/min (–0.07–0.70 mL/s) and the precision was 10.8−47.4 mL/min (0.18–0.88 mL/s). The Jelliffe 1973, Hull et al., and Mawer et al. equations were the least biased and the Jelliffe 1973 was the most precise, followed by the Mawer et al., Hull et al., and Cockcroft-Gault equations. The percent of patients with absolute percent errors >20 percent were 38 percent for Jelliffe 1973, 36 percent for Mawer et al., 40 percent for Hull et al., and >50 percent for the other equations. The percent of patients receiving correct drug doses was 67 percent for Jelliffe 1973, 58 percent for Gates, 51 percent for Mawer et al. and Hull et al., and <50 percent for the other equations. Within various age, renal function, serum creatinine, and albumin subgroups, the Jelliffe 1973 estimates were least biased and most precise, followed by the Cockcroft-Gault estimates. Generally, estimates using modified lean body weight performed better than did those using total body weight.

The Jelliffe 1973 equation with modified lean body weight was the best equation, followed by the Cockcroft-Gault equation. Even with the best equation, 33 percent of the patients would have received an incorrect drug dose. Therefore, some elderly patients may still require a measured creatinine clearance.

Phenylephrine uống được sử dụng như một thuốc giảm nghẹt mũi, nhưng chưa có bài đánh giá hệ thống nào được công bố trước đó hỗ trợ cho hiệu quả và an toàn của nó.

Đánh giá hiệu quả và an toàn của phenylephrine uống như một thuốc giảm nghẹt mũi không kê đơn.

MEDLINE, Cơ sở dữ liệu trung tâm của Thử nghiệm được kiểm soát của Cochrane, các Tóm tắt Dược phẩm Quốc tế EMBASE, và Đăng ký Liên bang đã được tìm kiếm cho các nghiên cứu bằng tiếng Anh và không tiếng Anh được công bố trước tháng 1/2007 mà đã đo lường tác dụng của phenylephrine uống đối với sức cản đường mũi (NAR) ở bệnh nhân nghẹt mũi. Các nghiên cứu thu thập được bổ sung thông tin từ các tệp cá nhân của chúng tôi và bằng cách tìm kiếm thủ công các tài liệu tham khảo. Ngoài ra, một tìm kiếm trên Web of Science đã được tiến hành sử dụng chức năng Tài liệu Tham khảo để tìm tất cả các thử nghiệm lâm sàng đã công bố. Các nghiên cứu được đưa vào phân tích là thử nghiệm có đối chứng ngẫu nhiên; các nghiên cứu về sản phẩm kết hợp bị loại trừ. Hai nhà điều tra đã độc lập trích xuất dữ liệu về NAR, tác dụng giảm nghẹt mũi tự báo cáo, và tác dụng với tim mạch (tức nhịp tim, huyết áp) từ mỗi nghiên cứu được đưa vào. Phân tích tổng hợp đã được thực hiện cho NAR và các tác dụng tim mạch sử dụng mô hình ngẫu nhiên. Tác dụng giảm nghẹt mũi chủ quan được tóm tắt.

Dựa trên 8 nghiên cứu chưa công bố bao gồm 138 bệnh nhân, phenylephrine 10 mg không ảnh hưởng NAR hơn so với giả dược; chênh lệch trung bình tối đa trong thay đổi tương đối từ cơ bản giữa phenylephrine và giả dược là 10.1% (95% CI −3.8% đến 23.9%). Tám nghiên cứu chưa công bố về phenylephrine 25 mg cho thấy sự giảm đáng kể NAR tối đa so với giả dược là 27.6% (95% CI 17.5% đến 37.7%). Có sự không đồng nhất đáng kể giữa các nghiên cứu được đưa vào phân tích này, một phần do các phòng thí nghiệm và phương pháp khác nhau được sử dụng. Không có dấu hiệu rõ ràng nào cho biết phenylephrine hiệu quả hơn giả dược, và NAR là thước đo nhạy cảm hơn về hiệu quả. Phenylephrine không ảnh hưởng đều đặn đến nhịp tim hay huyết áp đối với liều 25 mg hoặc ít hơn.

Không có đủ bằng chứng cho thấy phenylephrine uống có hiệu quả khi sử dụng không kê đơn như một thuốc giảm nghẹt mũi. Cục Quản lý Thực phẩm và Dược phẩm nên yêu cầu thêm các nghiên cứu để chứng minh tính an toàn và hiệu quả của phenylephrine.

Increasingly, hospitals are implementing multifaceted programs to improve medication reconciliation and transitions of care, often involving pharmacists.

To assess pharmacists' views on their roles in hospital-based medication reconciliation and discharge counseling and provide their recommendations for improving care transitions.

Eleven study pharmacists at 2 hospitals participated in the Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study and completed semistructured one-on-one interviews, which were coded systematically in NVivo. Pharmacists provided their perspectives on admission and discharge medication reconciliation, in-hospital patient counseling, provision of simple medication adherence aids (eg, pill box, illustrated daily medication schedule), and telephone follow-up.

Pharmacists indicated that they considered medication reconciliation, although time consuming, to be their most important role in improving care transitions, particularly through detection of errors that required correction in the admission medication history. They also identified patients who required additional counseling because of poor understanding of their medications. Providing adherence aids was felt to be highly valuable for patients with low health literacy, although less useful for patients with adequate health literacy. Pharmacists noted that having trained administrative staff conduct initial postdischarge follow-up calls to screen for issues and triage which patients needed pharmacist follow-up was helpful and an efficient use of resources. Pharmacists' recommendations for improving care transitions included clear communication among team members, protected time for discharge counseling, patient and family engagement in discharge counseling, and provision of patient education materials.

Pharmacists are well positioned to participate in hospital-based medication reconciliation, identify patients with poor medication understanding or adherence, and provide tailored patient counseling to improve transitions of care. Additional studies are needed to confirm these findings in other settings and to determine the efficacy and cost-effectiveness of different models of pharmacist involvement.

To evaluate the literature on supplemental vitamin C and vitamin E therapy in the prevention and treatment of Alzheimer's disease (AD).

Literature retrieval was accessed through MEDLINE (1966–March 2005) using the key words antioxidants, vitamin C, vitamin E, Alzheimer's disease, and dementia. International Pharmaceutical Abstracts (1970–March 2005), Current Contents (1996–March 2005), Cochrane Database of Systematic Reviews (1994–March 2005), and Ebsco's Academic Search Elite (1975–March 2005) were searched with the same key words.

Articles related to the objective that were identified through PubMed were included.

Oral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E ≥400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses ≥400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted.

In the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the lack of consistent efficacy data for vitamin C in preventing or treating AD should discourage its routine use for this purpose.

To report a case of probable acute venous thrombosis caused by heparin-induced thrombocytopenia (HIT) in a pediatric patient with a normal platelet count after prolonged enoxaparin therapy.

An 11-year-old African American female with Crohn's disease developed extensive vena cava thrombosis. Her deep vein thrombosis (DVT) was treated with intravenous unfractionated heparin followed by extended outpatient warfarin therapy. Four months later, the warfarin was stopped and subcutaneous enoxaparin 1.5 mg/kg once daily was substituted prior to an elective colonoscopy. She was readmitted 6 weeks later with acute DVT with a platelet count of 233 × 10 ³ /mm ³ , significantly lower than the count of 550–700 × 10 ³ /mm ³ 5 months previously and the count of 433 × 10 ³ /mm ³ 3 months earlier. An enzyme-linked immunosorbent assay for heparin-platelet factor 4 antibodies was strongly positive and a d-dimer was elevated at 2.9 mg/L (normal <1.5). She was treated with lepirudin followed by warfarin when repeat d-dimer on day 3 was normal. An ultrasound at that time showed no clot extension, and the platelet count had risen to >300 × 10 ³ /mm ³ . Over the next 4 months, there was no further thrombosis.

HIT appears to be rare in the pediatric population, and only a few cases treated with a direct thrombin inhibitor have been reported. This is the first case report to our knowledge of a pediatric patient developing HIT secondary to enoxaparin. An interesting feature of this case is the development of HIT in the face of a normal platelet count, which is rare but has been reported in adults.

Pediatric patients receiving low-molecular-weight heparin are still at risk for developing HIT. Treatment of HIT should involve the initial use of a direct thrombin inhibitor to manage thrombosis until the platelet count returns to higher values. Once the platelet count returns, warfarin can be used for long-term thrombosis management.

To report a case of acute renal failure associated with the administration of imatinib mesylate.

A 64-year-old man diagnosed with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus taxotere on a protocol that required a run-in period of imatinib mesylate alone. During therapy with imatinib mesylate, the patient developed acute renal failure, requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal failure resolved with cessation of imatinib mesylate.

Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Prostate cancer has been identified as a target for therapy with imatinib mesylate. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment determined that imatinib mesylate was the probable cause of the acute renal failure. The presence of a primary glomerular disease was excluded by biopsy.

Imatinib mesylate–induced acute renal failure has now been linked to toxic effects on renal tubular cells in 3 cases. Renal function should be closely monitored during imatinib mesylate therapy.

To review clinical information on the incidence and causes of hyponatremia (defined as a serum sodium level <130 mEq/L), the most common electrolyte abnormality seen in general hospital patients, and to discuss the diagnosis and treatment of hyponatremia in relation to these factors.

Primary sources and review articles were identified via MEDLINE (1981–July 2003) for entries on hyponatremia. We limited the search to specific topics including incidence, risk factors, diagnosis, treatment, and clinical disorders and medications associated with hypotonic hyponatremia.

All of the articles identified were evaluated, and relevant and representative information was included in this review.

Hyponatremia can result from several disease states, injury, surgery, physical exercise, or the administration of certain drugs (e.g., antidepressants, antiepileptics) and is associated with advanced age. Drug-induced hyponatremia is often asymptomatic and usually resolves following water restriction and monitoring of medication. Symptoms of hyponatremia are primarily neurologic; the principal danger of hyponatremia relates to effects on central nervous system function due to changes in brain size.

Although hyponatremia can be a serious condition, appropriate measures for the management of at-risk and affected patients will lead to full recovery in most cases.

To retrospectively evaluate clinical experiences with argatroban dosing, particularly incremental dosage adjustments, during a clinical trial of argatroban anticoagulation in heparin-induced thrombocytopenia (HIT).

Records of 304 patients with HIT administered argatroban during a prospective study were reviewed to determine each dose, incremental dosage adjustment, and duration of therapy. Dosing information (stratified by patient initial dose) and incremental adjustments (overall, and stratified by dose from which adjustment occurred) were summarized. The relationship between median incremental adjustments and adverse outcomes, including bleeding, was investigated.

Two hundred seventy-one (89%) patients received initial doses of 1.9–2.1 μg/kg/min (group B). Twenty-six (9%) patients were started at a lower dose. Group B's median (5–95th percentile) final dose was 1.6 (0.25–4.0) μg/kg/min. During a median of 6 days of argatroban therapy, patients underwent a median of 3.0 dosage adjustments using a median and mode incremental adjustment of 0.5 μg/kg/min (5–95th percentile, 0.1–2.0 μg/kg/min). Fifty-two (17%) patients required no dosage adjustment. Incremental adjustments decreased with decreasing current dose (e.g., median 0.25 μg/kg/min from doses of 0.26–0.75 μg/kg/min). Outcomes were similar between patients with no adjustment or with median incremental adjustments of ≤0.4, 0.41–0.75, or >0.75 μg/kg/min.

Based on this clinical experience, together with the established linear pharmacokinetics and pharmacodynamics of argatroban, appropriate dosage increments may be proposed for argatroban-treated patients with HIT. Incremental adjustments of 0.5 μg/kg/min are reasonable for most patients. Smaller adjustments (e.g., 0.25 μg/kg/min) should be used when modifying lower doses, such as those recommended for use in hepatically impaired patients.