Tolerability of enteric-coated didanosine capsules compared with didanosine tablets in adults with HIV infection.

BACKGROUND: A new enteric-coated (EC) didanosine (ddI) formulation (Videx EC; Bristol-Myers Squibb, Princeton, NJ, U.S.A.) may be better tolerated than the tablet form because it lacks the buffer component thought to be responsible for diarrhea and other gastrointestinal (GI) side effects. OBJECTIVE: To evaluate the frequency and magnitude of GI side effects (nausea, bloating, GI upset, diarrhea, abdominal cramps, gas [flatus]) before and after switching the formulation of ddI, in study subjects who were experiencing one or more GI symptom(s) of at least moderate severity. METHODS: A 6-week open label crossover study of current didanosine tablet users comparing daily symptom scores (7 point scale, 0 = absent to 6 = very severe) during weeks 1 to 2 (on tablets) to weeks 4 and 6 (on EC capsules). Formulation palatability and preference, lifestyle effects, and use of antidiarrheals or other medications for symptom relief were also assessed. RESULTS: GI symptom scores (7-day means) on tablets were diarrhea 2.11, gas 2.00, bloating 1.23, abdominal cramps 0.74, GI upset 0.69, nausea 0.66. After switching to EC (week 4 and week 6), mean scores decreased for diarrhea (mean scores 0.99 week 4, 0.79 week 6), gas (0.95, 0.79), bloating (0.49, 0.32), abdominal cramps (0.21, 0.05), GI upset (0.16, 0.14), and nausea (0.32, 0.22). Severity of all GI symptoms was significantly reduced after 4 weeks on EC capsules ( p <.01 by paired t- test). Negative impact of side effects on routine activities was significantly reduced (41% on tablet vs. 7% on EC; p <.01). All 42 study subjects preferred the EC form. CONCLUSIONS: According to patients' diary scores, switching to ddI in EC form significantly reduces nausea, bloating, GI upset, diarrhea, abdominal cramps, and gas for individuals who experienced GI side effects while taking the buffered tablet form. The striking tolerability advantages appear to support routine switching to EC for such patients and may suggest that widespread preferential selection of the EC form is appropriate to enhance didanosine tolerability and promote treatment adherence.

Patients' perceptions and responses to procedural pain: results from Thunder Project II.

BACKGROUND: Little is known about the painfulness of procedures commonly performed in acute and critical care settings. OBJECTIVE: To describe pain associated with turning, wound drain removal, tracheal suctioning, femoral catheter removal, placement of a central venous catheter, and nonburn wound dressing change and frequency of use of analgesics during procedures. METHODS: A comparative, descriptive design was used. Numeric rating scales were used to measure pain intensity and procedural distress; word lists, to measure pain quality. RESULTS: Data were obtained from 6201 patients: 176 younger than 18 years and 5957 adults. Mean pain intensity scores for turning and tracheal suctioning were 2.80 and 3.00, respectively (scale, 0-5), for 4- to 7-year-olds and 52.0 and 28.1 (scale, 0-100) for 8- to 12-year-olds. For adolescents, mean pain intensity scores for wound dressing change, turning, tracheal suctioning, and wound drain removal were 5 to 7 (scale, 0-10); mean procedural distress scores were 4.83 to 6.00 (scale, 0-10). In adults, mean pain intensity scores for all procedures were 2.65 to 4.93 (scale, 0-10); mean procedural distress scores were 1.89 to 3.47 (scale, 0-10). The most painful and distressing procedures were turning for adults and wound care for adolescents. Procedural pain was often described as sharp, stinging, stabbing, shooting, and awful. Less than 20% of patients received opiates before procedures. CONCLUSIONS: Procedural pain varies considerably and is procedure specific. Because procedures are performed so often, more individualized attention to preparation for and control of procedural pain is warranted.

Translating research into practice. Implications of the Thunder Project II.

The Thunder Project II study described procedural pain in a variety of acute and critical care settings. The procedures studied were turning, tracheal suctioning, wound drain removal, nonburn wound dressing change, femoral sheath removal, and central venous catheter insertion. Turning had the highest mean pain intensity, whereas femoral sheath removal and central venous catheter insertion had the least pain intensity in adults. Nonwound dressing change had the highest pain intensity for teenagers. Pain occurred in procedures that are often repeated several times a day as well as in those that may be single events. There is a wide range of pain responses to any of these procedures; as a result, standardized and thoughtful pain, and distress assessments are warranted. Planning of care, including the use of preemptive analgesic interventions, needs to be individualized. Future studies are needed to describe patient responses to other commonly performed nursing procedures and to identify effective interventions for reducing procedural pain and distress.

Multicenter review of protease inhibitors in 89 pregnancies.

CONTEXT: Despite the success of highly active antiretroviral therapy, the optimal approach for preventing perinatal HIV-1 transmission is not known. OBJECTIVE: A retrospective survey was conducted at six centers in the United States and Puerto Rico from January 1997 to October 1998 to evaluate the effects of protease inhibitor use during pregnancy on maternal and infant safety, prematurity rate, and frequency of perinatal HIV-1 transmission. RESULTS: In the study, 91 live infants, including 3 sets of twins, and 1 neonate who died shortly after birth were born to 89 women. HIV perinatal transmission rate in this series was 0 (95% confidence interval [CI], 0%-3%). Prematurity rate was 19.1%, comparable to rates in earlier reports of HIV-1-infected women. In multiple regression analysis, only cocaine use and premature rupture of membranes were associated with prematurity (p =.03 and.008, respectively). The gestational week during which the protease inhibitors were initiated was not found to be significantly associated with prematurity. Adverse maternal, obstetric, and infant events possibly related to protease inhibitors were uncommon. CONCLUSIONS: Protease inhibitors appeared generally safe in mothers and infants in this series. No perinatal HIV-1 transmission occurred. Further prospective, controlled studies are needed to define the optimal management of HIV-1 in pregnancy.

Versatile, high-speed force transducer using a laser diode beam as an optical lever.

A force transducer with variable sensitivity and speed is described. Its moving element is a cantilever beam that projects vertically into a muscle bath. A brace constrains bending of the beam to a short, proximal "hinge." Rotation of the beam about the hinge is amplified 30-fold by an optical lever consisting of a laser diode beam reflected from a mirror on the cantilever to a photodiode pair. This design places the electrical components at a distance from the damp environment of the muscle bath. Large changes in sensitivity and speed can be obtained by substituting different cantilevers. Smaller changes can be made by varying the length of the hinge. A transducer with a 6-mm cantilever optimized for the study of single, skinned skeletal muscle fibers is described in detail. This device had a resonant frequency of 22 kHz and sensitivity such that the total root-mean-square noise in the circuit was more than 500-fold smaller than the expected maximum force. Variations of this device with orders of magnitude different sensitivities are also described.

Failure to cure Mycobacterium gordonae peritonitis associated with continuous ambulatory peritoneal dialysis.

Nontuberculous mycobacteria are increasingly recognized as important pathogens in peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Mycobacterium gordonae rarely causes human infection and is the least likely mycobacterium to produce clinical infection in CAPD patients. We describe a patient with persistent M. gordonae peritonitis acquired while undergoing CAPD. During 18 months of treatment, clinical improvement occurred but a microbiological cure could not be achieved. Principles of therapy for mycobacterial peritonitis developing during CAPD are reviewed, and potential explanations for our patient's failure to respond to therapy are discussed.

Sinonasal non-Hodgkin's lymphoma in patients infected with human immunodeficiency virus: report of three cases and review.

Non-Hodgkin's lymphoma (NHL) is a frequent complication of human immunodeficiency virus (HIV) infection, but involvement of the sinonasal region has only rarely been reported. We report three cases of AIDS-associated sinonasal NHL that occurred at our institution and review eight cases that were reported in the literature. The epidemiological and clinicopathologic features of these cases are described and compared with those of three other groups of patients: non-HIV-infected patients with sinonasal NHL, HIV-infected patients with NHL of any anatomic site, and HIV-infected patients with infectious sinusitis. Patients with AIDS-associated sinonasal NHL more frequently developed bony erosion and presented with signs and symptoms referable to adjacent structures, such as the orbit, than did HIV-infected patients with sinusitis, and patients with AIDS and NHL less frequently had typical sinus symptoms and diffuse sinus involvement than did patients with sinusitis. However, the clinical manifestations of these conditions overlap; thus a high index of suspicion for NHL is imperative for prompt diagnosis. These lymphomas typically are high-grade and disseminate early, and the prognosis is generally poor.

Use of rifampin in nonstaphylococcal, nonmycobacterial disease.

Rifampin has very broad antimicrobial properties with in vitro activities against many bacteria, mycobacteria, higher bacteria, chlamydia, fungi, parasites, and viruses (Table 1). The clinical use of rifampin is more limited, in part because of the lack of in vivo human clinical studies demonstrating its efficacy. Investigators have valid concerns regarding the emergence of resistance of mycobacteria if widespread use of rifampin becomes common, although this has not been well documented. Because rifampin obtains therapeutic levels intracellularly and is distributed widely throughout the body, the antibiotic potentially could be used on a broader scale, but more studies will be needed to demonstrate its clinical utility.

Gallbladder and biliary tract candidiasis: nine cases and review.

We review biliary tract and gallbladder candidiasis and define patient demographics, risk factors, prognostic factors, and treatment strategies for this infection. This is a 3-year retrospective review of our experience with this disease and a review of the English-language literature. Thirty-one cases of biliary tract and gallbladder candidiasis, including nine in our series, have been examined. The same risk factors that predispose patients to other forms of candidal infection are implicated here. No mortality was found with uncomplicated candidal cholecystitis in nonneutropenic patients treated with cholecystectomy alone. Patients with associated extrabiliary tract candidiasis or candidemia had worse outcomes and required both surgical intervention and antifungal therapy. When risk factors exist for the development of biliary tract or gallbladder candidiasis, the physician should be alert to this possibility. There is no need for antifungal therapy in cases of isolated candidiasis of the gallbladder in nonneutropenic patients.