Elizabeth C. Reed

Treatment of Cytomegalovirus Pneumonia with Ganciclovir and Intravenous Cytomegalovirus Immunoglobulin in Patients with Bone Marrow Transplants

STUDY OBJECTIVE To determine if the combination of ganciclovir and intravenous cytomegalovirus immunoglobulin is effective in patients with cytomegalovirus pneumonia after bone marrow transplant. DESIGN Consecutive entry trial with treatment for a minimum of 14 days. PATIENTS Consecutive sample of 25 patients with bone marrow transplants and cytomegalovirus pneumonia after transplant proven by open lung biopsy or bronchoalveolar lavage. Patients with abnormal renal function or concomitant infectious causes of pneumonia, or who were respirator-dependent at diagnosis, were not eligible. INTERVENTIONS Induction treatment consisted of ganciclovir, 2.5 mg/kg body weight every 8 hours for 14 days, and cytomegalovirus immunoglobulin, 400 mg/kg on days 1, 2, and 7 and 200 mg/kg on day 14. Ganciclovir dosage was adjusted for renal function. Patients who were improved but still symptomatic after 14 days were given maintenance treatment consisting of ganciclovir, 5 mg/kg once daily for an additional 14 days, and immunoglobulin, 200 mg/kg on day 21. Patients with clinical deterioration continued to receive induction doses. Ganciclovir therapy was discontinued if the neutrophil count fell below 500 X 10(6)/L for 2 consecutive days. MEASUREMENT AND MAIN RESULTS Serial tests of renal and liver function, blood counts, and viral cultures of blood, throat, and urine were obtained 3 times a week. Thirteen of twenty-five (52%) patients (95% CI, 31 to 72) survived the initial episode of pneumonia. Viral excretion ceased in 17 of 23 (74%) patients treated more than 96 hours. Proven recurrences of pneumonia occurred in 3 patients and possible recurrences in 2 after treatment was stopped. Three patients developed neutropenia during induction therapy and 6 patients during maintenance therapy. CONCLUSIONS Survival of 13 (52%) of 25 patients from the initial episode of cytomegalovirus pneumonia with the regimen of ganciclovir and cytomegalovirus immunoglobulin is significantly better (P less than 0.001) than the survival of 13 of 89 (15%) patients using previous antiviral regimens.

Acyclovir for Prevention of Cytomegalovirus Infection and Disease after Allogeneic Marrow Transplantation

Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.

Treatment of Handwriting Problems in Beginning Writers: Transfer from Handwriting to Composition.

Almost 700 children were screened to identify 144 1st graders at risk for handwriting problems who were randomly assigned to 1 of 6 treatment conditions. Treatment was delivered to groups of 3 that met twice a week in 20-min sessions until they completed 24 lessons. Five groups received 10 min of different kinds of handwriting instruction. The contact control group received 10 min of phonological awareness training. All 6 groups composed and shared their writing for 10 min. Converging evidence across multiple measures showed that combining numbered arrows and memory retrieval was the most effective treatment for improving both handwriting and compositional fluency (composing with time limits). Thus instruction aimed at improving transcription transfers to improved text generation in beginning writers.

Early intervention for spelling problems: Teaching functional spelling units of varying size with a multiple-connections framework.

Poor spellers in 2nd grade (n = 128) participated in 24 20-min sessions that included (a) direct instruction in the alphabet principle (most frequent phoneme-spelling connections); (b) modeling of different approaches, singly and in combination, for developing connections between spoken and written words for 48 words ordered by sound-spelling predictability; and (c) practice in composing. Results of this multilayered intervention showed that (a) more than 1 way of developing sound-spelling connections is effective in teaching spelling but that after training in the alphabet principle, combining whole word and onset-rime training is most effective in achieving transfer of the alphabet principle across word contexts; (b) functional spelling units of not only a single letter but also 2 or more letters are important in beginning spelling; and (c) training in spelling transfers to composition and word recognition.

Ganciclovir for the Treatment of Cytomegalovirus Gastroenteritis in Bone Marrow Transplant Patients: A Randomized, Placebo-Controlled Trial

STUDY OBJECTIVE To determine the efficacy of ganciclovir for the treatment of cytomegalovirus enteritis after bone marrow transplant. DESIGN A randomized, double-blind, placebo-controlled trial. SETTING Inpatient units of a cancer center. PATIENTS Consecutive patients with biopsy-documented cytomegalovirus infection of the gastrointestinal tract. Cytomegalovirus was identified by culture or by immunohistologic or standard histologic analysis. INTERVENTIONS Ganciclovir, 2.5 mg/kg body weight every 8 hours for 14 days, or placebo, with dosage adjusted for decreases in renal function. Therapy was discontinued if the neutrophil count or creatinine clearance fell below preset criteria. MEASUREMENTS AND MAIN RESULTS Virus cultures of throat, urine, and blood specimens were done before, 3 times weekly during, and weekly for 3 weeks after therapy. Endoscopy was repeated after treatment. Patients were examined, and blood counts, electrolytes, and renal and hepatic function were monitored during therapy. Ganciclovir recipients had cessation of oropharyngeal (P = 0.001) and urinary (P = 0.004) cytomegalovirus excretion and negative cultures of repeat esophageal specimens (P = 0.002) more often than placebo recipients. No difference existed in either clinical symptoms or endoscopic appearance between the groups after treatment. Cytomegalovirus pneumonia occurred in four patients who received ganciclovir and in six who received placebo. One ganciclovir recipient and four placebo recipients were withdrawn from treatment because of neutropenia, but there was no overall difference in the proportional decrease in leukocyte counts between groups. CONCLUSIONS Although ganciclovir suppressed cytomegalovirus replication, 2 weeks of treatment was not associated with clinical or endoscopic improvement when compared with supportive care.

Teaching Spelling to Children with Specific Learning Disabilities: The Mind's Ear and Eye Beat the Computer or Pencil.

Children with only spelling (n=24) or handwriting and spelling disabilities (n=24) were randomly assigned to a pencil or computer response mode. They were taught 48 words of varying orders of sound-spelling predictability using a method that emphasized hearing the word in the minds ear and seeing the word in the minds eye and making connections between the phonological and orthographic representations at the whole word and subword levels. Although no main effects were found for response mode, at posttest the pencil was superior to the computer for easy orders (single-letter spelling units with high sound-spelling predictability), but the computer was superior to the pencil for moderate and difficult orders (multiletter spelling units with intermediate or low sound-spelling predictability). Prior to and in response to treatment, children with handwriting and spelling problems spelled less well than children with only spelling problems. Multiletter spelling units of moderate or difficult orders of sound-spelling predictability explained unique increments of variance in spelling achievement, whereas single-letter spelling units of easy order of sound-spelling predictability did not. Based on these findings, instructional recommendations are to provide explicit instruction in the correspondence between sound and multiletter spelling units.

Year-Long Balanced Reading/Writing Tutorial: A Design Experiment Used for Dynamic Assessment

Sixteen children referred for severe reading problems in first grade participated in a year-long individual tutorial. The tutorial, which was designed to bring children up to expected level based on ability and grade in reading and writing, lasted from the end of first grade to the end of second grade. Growth curve analyses for the group on measures of orthographic and phonological coding, word identification of real words, word attack of pseudowords, reading comprehension, letter automaticity, and spelling showed that gains were significantly greater than chance. Growth curves for the group were marginally significant for written composition. Individual subject analysis revealed that most children were treatment responders (i.e., growth significantly greater than chance) on most of the measures and all reached expected levels, based on ability or grade, on some of the measures. Results have implications for analysis of response to intervention in reading and writing as a form of dynamic assessment.