Weeks Of Initial Diagnosis Research Articles

Prescription patterns and symptom relief of antitussives and expectorants in patients with cough: a nationwide study in Korea.

Limited data are available on the prescription patterns and efficacy of antitussives and expectorants for patients with acute and chronic cough. This study examined the use and efficacy of these medications in a nationally representative sample of Korean patients. We examined 4,206,016 individuals from the National Health Insurance Service (NHIS)-National Health Information Database (NHID) between 2015 and 2017. Among them, a sample of 10% (n=420,602) was retrieved for the diagnosis of respiratory diseases using the International Classification of Diseases, 10th edition (ICD-10; J00-J99), or the prescription of antitussives and expectorants for cough (ICD-10; R05). The acute cough group included those who were prescribed medications within 4 weeks of initial diagnosis (prescription within 14 days), whereas the chronic cough group included patients who were prescribed medications within 16 weeks of initial diagnosis (prescription within 56 days). If the prescription was discontinued or not changed to an alternative drug after the initial prescription, these cases were considered to have achieved symptom relief. This study included 288,460 patients (971,065 cases) with acute cough and 5,888 patients (15,399 cases) with chronic cough. 'Expectorants, excluding combinations with cough suppressants' had the highest prescription rates in both groups (acute cough, 63.8%; chronic cough, 61.7%), and showed the highest symptom relief regardless of the number of medications prescribed (acute cough, 84.3%; chronic cough, 70.4%). 'Expectorants, excluding combinations with cough suppressants' were the most prescribed and effective medications for relieving cough symptoms in Korea patients. Further studies are needed to determine the optimal duration for using antitussives and expectorants in cough management.

Surgical management of complicated Descemet’s membrane detachment in corneas without prior endothelial keratoplasty

PurposeTo provide insights into morphologic and functional features of eyes with complicated Descemet's membrane detachment (DMD) and report clinical outcomes after surgical intervention.MethodsRetrospective study of 18 eyes with complicated DMD between 2010 and 2022. Complicated DMD was defined if any of the following criteria applied: prior penetrating keratoplasty (PKP), corneal thinning, total DMD or persistent DMD after Air/Gas-Descemetopexy. Causes, surgical management, and clinical outcomes were analyzed. Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT) and histologic examination were performed to characterize corneas with DMD.ResultsFourteen eyes with prior PKP developed spontaneous DMD after 24.2 ± 12.9 years (range = 18 months – 47 years, median = 25.7 years). Complicated DMD without prior PKP was associated in three eyes after cataract surgery and in one eye after infectious keratitis. In cases with previous PKP, AS-OCT demonstrated rupture of Descemet’s membrane (DM) in five eyes and spontaneous reattachment was found in four eyes within 8 weeks of initial diagnosis, with no rupture of DM in any of the cases. There was no rupture of DM in corneas without previous PKP. After prior keratoplasty, definitive surgical treatment was repeat PKP in 13 eyes and Air/Gas-Descemetopexy in one eye. In corneas without prior keratoplasty, three eyes underwent PKP and one eye Air/Gas-Descemetopexy. Histological examination of two corneal explants revealed a severely thinned graft-host junction and a disrupted DM close to the graft-host junction. Visual acuity improved from 1.80 ± 0.58 logMAR to 0.75 ± 0.69 logMAR after prior PKP and from 1.45 ± 0.65 logMAR to 0.85 ± 1.13 logMAR without prior PKP. The postoperative course was uneventful in 16 of 18 eyes.ConclusionPKP is an effective treatment option for complicated DMD, especially in ectatic corneas, whereas Air/Gas-Descemetopexy or Descemet Membrane Endothelial Keratoplasty do not address the primary issue of the curvature anomaly.

P16 Orthoptic led eye screening co-located within the paediatric rheumatology clinic for safer management of children with JIA

Abstract Background Juvenile idiopathic arthritis (JIA) affects 1 in 1000 children. Around 10% to 30% of children with JIA develop anterior uveitis. Particularly in the oligoarticular subtype, this uveitis is chronic and therefore asymptomatic, without the classical red eye and pain of acute uveitis. This leads to insidious but progressive visual loss if unrecognised. Although young age, oligoarticular disease and positive ANA are risk factors for uveitis, these factors are not required, and it can occur at any point in disease course. Hence, it is essential that patients who are diagnosed with JIA have prompt and regular eye screening. Diagnosis of uveitis by slit-lamp examination is essential. Both British Society for Rheumatology and Royal College of Ophthalmologists guidelines recommend initial slit-lamp screening in asymptomatic patients within 6 weeks of initial diagnosis, and then every 3-4 months until the age of 12. A 2014 audit of paediatric rheumatology services in the East of England revealed significant variation between trusts (between 9%-100%) with an average 35.4% of patients with first visit within 6 weeks. In our hospital, less than 25% met this standard. These results showed the need for a more robust pathway. Methods The poor performance at Southend in 2012 was due to lack of capacity in general paediatric ophthalmology clinic, despite a prompt referral process, with delays and frequent non-attendance for follow-up screening in existing patients. A slit lamp was obtained to be kept in the Paediatric outpatient department. JIA eye screening clinic was set up in December 2017, running weekly alongside the Rheumatology clinic. This ensures that patients received timely and convenient eye screening as a ‘one-stop’ visit. It also frees capacity in the Eye Unit. New and follow-up patients with JIA are reviewed, with assessment of visual acuity, orthoptic assessment, followed by slit-lamp examination. Exclusions for this clinic include children under 3 years old, uncooperative youngerchildren, and those with uveitis, who are reviewed in the eye unit as previously. Results In the initial 18-month period (2017-2019), 41 separate patients were seen across 108 attended appointments. 75% new referrals were reviewed within 6 weeks, 66.6% were seen at 2 monthly intervals for the first 6 months post diagnosis. 7.3% were referred to paediatric ophthalmology consultant. Delays were mainly seen early on as the process was being established. Conclusion Issues with capacity in Ophthalmology resulted in significant delays to eye-screening appointments. The orthoptic-led clinic has improved our compliance with national guidelines, allowed for improved communication between the two specialities, ensured timely follow-ups, reduced school time missed and improved patient experience. Multi-disciplinary input is made easier by reviewing in one session, minimising non-attendances. Disclosures A. Bouraoui: None. L. roberts: None. A. Landells: None. E. Law: None. V. geh: None. A. Shrivastava: None. F. Borg: None.

2057 Refractory Fulminant Ulcerative Colitis With Concurrent Clostridioides difficile Colitis Challenging Modern Guideline-Directed Medical Therapy to Failure

INTRODUCTION: Guidelines on treatment of ulcerative colitis (UC) follow a stepwise approach of escalating medical therapy. Similarly, treatment guidelines for Clostridioides difficile infection (CDI) are well-established based on severity. The combination of fulminant UC & CDI especially patients with treatment naïve pancolitis is challenging with concerns for safety & efficacy of various therapies in concurrent conditions. CASE DESCRIPTION/METHODS: A 21-year-old male presented with 3 weeks of diarrhea, hematochezia & abdominal pain. Stool cultures & CD were negative & antibiotics were started. Subsequent colonoscopy showed pancolitis & UC on biopsy. IV steroids & probiotics were initiated with modest improvement & he was discharged. However, he was readmitted with worsening symptoms, started on IV steroids. Repeated colonoscopy with biopsies confirmed moderate active chronic colitis with focal ulceration & no granulomas or dysplasia. CD testing was positive. Hence, PO vancomycin was started. He had IBD-related arthritis & was started on sulfasalazine then methotrexate (MTX). Response to IV steroids (10 days) & PO vancomycin (14 days) was limited, therefore with infliximab was started. Vancomycin was switched to fidaxomicin with IVIG (3 doses). Colonoscopy was repeated revealing ongoing severe pancolitis with pseudomembrane, Mayo grade 3. Fecal microbiota transplant (FMT) was done. Biopsies were negative for CMV. Follow up CD testing was negative, yet, he progressed to fulminant UC within 6 weeks of initial diagnosis despite 4 doses of infliximab & steroids. He remained hemodynamically stable with supportive care. He was reluctant to have colectomy & hence tofacitinib was started. Despite IV steroids, infliximab, & tofacitinib; sulfasalazine & MTX; parallel PO vancomycin, fidaxomicin, IVIG & FMT, along with lactobacillus acidophilus, bloody diarrhea continued; patient was dependent on fluid support & blood transfusions. Finally, total colectomy was done as a last resort. DISCUSSION: Guidelines are lacking on treatment of concurrent refractory fulminant UC with CDI especially in patients who do not want colectomy. Potential success of biologic therapy & risk of progression to fulminant CDI in this setting is unknown. Safety & efficacy of the various treatments including immunosuppressants & FMT in cases of concurrent UC & CDI is a grey zone. Further case-reports & studies are needed to establish the optimal stepwise approach & guide therapeutic choice & decision making.

Leptomeningeal Carcinomatosis From Gastric Signet Ring Cell Carcinoma Presenting With SIADH and Neurological Symptoms

Introduction: Leptomeningeal carcinomatosis (LMC) is a rare but ominous complication of metastatic gastric cancer. LMC is found in 3-8% of all solid cancers and is generally a manifestation of advanced disease usually discovered late in the treatment phase. We report the case of a young man with LMC in the form of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and seizures as presenting findings of metastatic gastric signet ring cell carcinoma. Case: 47-year old Hispanic man presented with transient episodes of blank stares and gaze deviation followed by loss of consciousness and post-ictal confusion. There was no significant medical history reported; however, review of systems was remarkable for two-month history of occipital headaches, nausea, loss of appetite and a forty-pound weight loss. Laboratory results were significant for hyponatremia (sodium level 122) and urine studies suggested SIADH. CT scan of the abdomen revealed a thickened gastric wall with extensive lymphadenopathy. Esophagogastroduodenoscopy was concerning for linitis plastica (Figure 1). Biopsies confirmed high grade invasive signet ring cell adenocarcinoma. Hospital course was complicated by worsening headaches and nuchal rigidity. MRI of the brain showed findings suggestive of LMC. CSF cytology depicted malignant cells similar in morphology to concurrent gastric surgical pathology specimen (Figure 2). Given advanced intra-abdominal involvement and spread to the leptomeninges, systemic chemotherapy was not offered. Patient and his family opted for palliative therapy, and within two weeks of initial diagnosis, he passed away due to deteriorating neurological function.Figure: Esophagogastroduodenoscopy showing diffuse infiltrating gastric cancer (linitis plastica).Figure: Above: CSF cytology with clusters of signet ring cells. Below: Gastric biopsy showing diffuse sheets of signet ring cells.Discussion: LMC is a rare but devastating complication of advanced cancer. Patients present relatively acutely, with symptoms emerging over days to weeks. Its incidence due to gastric cancer is approximately 0.14-0.24%; with signet ring type morphology having greatest tendency for metastasis to the brain. It has been hypothesized that tumor cells spread via arterial circulation, Batson's venous plexus, perineural spaces or lymphatics, and direct infiltration. Overall prognosis remains poor with median survival of 3-4 months. Hence, palliative care remains mainstay of management. Our case highlights not only the occult nature of this type of gastric cancer but also provides insight into the importance of comprehensive assessment for underlying malignancy in patients with SIADH neurological symptoms.

PD51-11 FACTORS PREDICTING SURGICAL INTERVENTION IN PEDIATRIC NEPHROLITHIASIS PATIENTS

INTRODUCTION AND OBJECTIVES: Nephrolithiasis is an increasingly common disease process often requiring extensive followup and care with significant economic ramifications. Computed tomography (CT) remains the preferred initial diagnostic modality due to its excellent sensitivity and specificity for stone disease. Medical expulsive therapy is a reasonable course of treatment for many patients but often results in a protracted clinical course. Concern regarding overutilization of CT with respect to increased radiation exposure and health care costs has been expressed. We sought to identify patients with known urinary tract calculi who undergo additional CT imaging between initial diagnosis and stone passage or intervention to determine if their management is altered by the additional imaging study. METHODS: Retrospective chart review of all urinary stone patients (by ICD-9 code) between January 2009 and January 2012 was performed. We identified those patients who had repeat CT imaging performed within six weeks of the initial urinary stone diagnosis for the same indication. Charts were examined to determine if additional information was gained through repeat CT imaging and if the repeat CT scan altered course of stone management. RESULTS: 1119 patients were identified. 128 patients (11%) met inclusion criteria with repeat CT scan. Repeat CT scan (within 6 weeks of initial diagnosis) resulted in a change in planned management in 9/128 patients (7%). Average additional radiation dose per patient was 36.9 mSv. Thirty-six patients underwent CT imaging for flank pain even after a ureteral stent had previously been placed. CONCLUSIONS: Many patients undergo unnecessary repeat CT imaging for kidney stones leading to increased cost and radiation exposure. Only 7% of patients who underwent repeat CT imaging had an alteration in the previously planned management for known kidney stones. Repeat imaging with CT is rarely necessary in the short-term management of nephrolithiasis. Following a diagnosis of nephrolithiasis, additional follow-up information and progress may be acquired through physical exam, laboratory values, and possibly ultrasound examination limiting cost and cumulative radiation exposure.

PD51-10 OVERUTILIZATION OF CT IMAGING IN PATIENTS WITH KNOWN URINARY TRACT CALCULI

INTRODUCTION AND OBJECTIVES: Nephrolithiasis is an increasingly common disease process often requiring extensive followup and care with significant economic ramifications. Computed tomography (CT) remains the preferred initial diagnostic modality due to its excellent sensitivity and specificity for stone disease. Medical expulsive therapy is a reasonable course of treatment for many patients but often results in a protracted clinical course. Concern regarding overutilization of CT with respect to increased radiation exposure and health care costs has been expressed. We sought to identify patients with known urinary tract calculi who undergo additional CT imaging between initial diagnosis and stone passage or intervention to determine if their management is altered by the additional imaging study. METHODS: Retrospective chart review of all urinary stone patients (by ICD-9 code) between January 2009 and January 2012 was performed. We identified those patients who had repeat CT imaging performed within six weeks of the initial urinary stone diagnosis for the same indication. Charts were examined to determine if additional information was gained through repeat CT imaging and if the repeat CT scan altered course of stone management. RESULTS: 1119 patients were identified. 128 patients (11%) met inclusion criteria with repeat CT scan. Repeat CT scan (within 6 weeks of initial diagnosis) resulted in a change in planned management in 9/128 patients (7%). Average additional radiation dose per patient was 36.9 mSv. Thirty-six patients underwent CT imaging for flank pain even after a ureteral stent had previously been placed. CONCLUSIONS: Many patients undergo unnecessary repeat CT imaging for kidney stones leading to increased cost and radiation exposure. Only 7% of patients who underwent repeat CT imaging had an alteration in the previously planned management for known kidney stones. Repeat imaging with CT is rarely necessary in the short-term management of nephrolithiasis. Following a diagnosis of nephrolithiasis, additional follow-up information and progress may be acquired through physical exam, laboratory values, and possibly ultrasound examination limiting cost and cumulative radiation exposure.

Outcomes of Fidaxomicin Treatment of Clostridium difficile Infection

Introduction: Fidaxomicin is a narrow spectrum macrocyclic antibiotic used for the treatment of Clostridium difficile infection (CDI). The aim of this study was to evaluate response and recurrence rates of CDI after treatment with fidaxomicin. Methods: All potential cases of CDI treated with fidaxomicin at our institution over a 3-year period were identified using an electronic search of medical records. Criteria for study inclusion included a definite diagnosis of CDI and treatment with fidaxomicin 200 mg twice daily for 10 days. Data collected included demographic information, number of prior CDI episodes, prior CDI treatment, response to fidaxomicin, recurrence after treatment, and medication adverse effects. Response to treatment was defined by the resolution of diarrhea after treatment. In cases where diarrhea did not resolve, a primary non-response was recorded. Recurrent CDI was defined if diagnostic criteria were met within 8 weeks of initial diagnosis after documented symptom resolution. Diarrhea recurring after 8 weeks of resolution was considered a new episode. Results: Twenty-six patients with CDI were treated with fidaxomicin. The median age was 50 years; 62% were female; 31% had concurrent inflammatory bowel disease (IBD). Most patients (85%) had prior episodes of CDI with a median of 2 previous episodes (range: 0-8). All patients had prior treatments for CDI, 89% with metronidazole, and 81% with vancomycin; 70% had previous treatment with both medications. Complete response was noted in 22 patients (85%), while 4 patients (15%) had no response. However, 55% of responders had recurrent CDI within 8 weeks of diarrhea resolution. Responders who did not recur had fewer prior episodes of CDI (median 1; range: 0-3) than patients who recurred (median 2.5; range: 1-8) or had no response to fidaxomicin (median 2; range: 1-8). All patients (n=4) treated with fidaxomicin for a first episode of CDI responded with resolution of diarrhea with no recurrences. All patients with IBD (n=8) responded to fidaxomicin with resolution of diarrhea, although 62% experienced recurrent CDI. There were no adverse events reported with fidaxomicin. Conclusion: Fidaxomicin is effective in treating CDI in clinical practice, including patients with recurrent infection and IBD. All patients treated with fidaxomicin for a first episode of CDI responded with resolution of diarrhea with no recurrences. However, patients with multiple s before treatment with fidaxomicin had a high rate of further recurrences. Disclosure - Dr. Pardi - Served on an advisory board and was paid an honorarium by Cubist.

Outpatient Surveillance Protocol of Isolated Calf Deep-Vein Thrombosis

Objectives This study aims to compare the management of isolated soleal, gastrocnemius, peroneal, and posterior tibial vein thrombosis among outpatients with serial duplex ultrasound (DUS) over 30 days, versus anticoagulation. Methods After obtaining IRB approval, a retrospective chart review was conducted from January 2009 to December 2010. A total of 15, 877 lower extremity DUS were performed. Inpatients, trauma patients, and patients with thrombi in or proximal to the popliteal vein were excluded to focus exclusively on an unprovoked outpatient population. Univariate and multivariate analyses were conducted as well as descriptive statistics of the data. Results The cohort consists of one hundred sixty-eight (n = 168) outpatients with isolated calf deep vein thrombosis (ICDVT). Thrombus was most frequently identified in the soleal vein (45%) followed by the peroneal (39%), gastrocnemius (29%), and the posterior tibial vein (23%). Following diagnosis of ICDVT, thirty-eight patients (n = 38) received anticoagulation. The remaining cohort (n = 130) underwent surveillance with serial DUS at 3, 10, and 30 days. Eleven percent (11%) propagated to the popliteal vein or proximally during surveillance, versus 8% following anticoagulation. Among those that propagated proximally, 85% propagated within two weeks of initial diagnosis. Proximal propagation ( p = 0.8328), pulmonary embolism ( p = 0.0537), and development of new thrombus in additional calf veins ( p = 0.1471) did not differ among those treated with anticoagulation or serial DUS. Conclusions Serial DUS without anticoagulation is safe management of ICDVT in unprovoked ambulatory outpatients.

Effect of valproic acid on the outcome of glioblastoma multiforme

Background. Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor. It is a rapidly progressive, highly recurrent, fatal intracranial neoplasm, and the demand for novel treatment is urgent. Valproic acid (VPA) is a potential anticancer agent that belongs to a class of histone deacetylase (HDAC) inhibitors, targeting the epigenetic control of gene functions in cancer cells. This drug has been administered for the prevention or treatment of seizure disorder in GBM patients; therefore, a retrospective analysis may further our understanding of the effect of VPA on GBM patients. Materials and methods. A retrospective analysis of 102 patients with GBM was conducted to study the effects of VPA on disease outcome. Tumor samples from seven patients receiving VPA treatment between the first and second operations were obtained in order to verify the HDAC inhibitory activity of VPA in these patients. Results. In univariate analysis, administration of VPA within 2 weeks of initial diagnosis seemed to confer a survival benefit. However, stratified analysis according to chemotherapy showed that VPA did not have significant impact on the GBM patients’ overall survival. Analysis of tissue samples from these patients revealed that a small subset of patients had increased histone acetylation after VPA treatment. Conclusion. VPA treatment, when administered according to a protocol targeting seizure control, may result in HDAC inhibition in a small subset of patients, but does not significantly affect overall patient survival. Early administration of VPA as an adjunct to temozolomide chemotherapy may have its merits, but the optimal dosing schedule and target serum level require further investigation.

Predictors of Hospitalization in Community-acquired Clostridium difficile Infection: A Population-based Study

Purpose: Community-acquired Clostridium difficile infection (CA-CDI) is an increasingly recognized cause of diarrhea, including those who were previously thought to be at low risk or lacked traditional risk factors. Outcomes of CA-CDI have not been routinely examined. Therefore, we assessed predictors of hospitalization in a population-based cohort of CA-CDI. Methods: A computerized diagnostic index, which captured all inpatient and outpatient medical encounters for Olmsted County residents, was used to identify CDI cases from 1991-2005. Medical records were reviewed to confirm the diagnosis, document demographic data, and assess treatment outcomes. CDI was defined as community-acquired if symptom onset occurred in the community or within 48 hours of hospital admission, provided symptom onset was more than 4 weeks after the last hospital discharge. Severe CDI was defined by a peripheral white blood cell count ≥ 15,000/uL or a serum creatinine rise of ≥ 50% from baseline. Recurrent CDI was defined if diagnostic criteria were met within 8 weeks of initial diagnosis after documented symptom resolution. Treatment failure was defined as change in treatment within 14 days due to non-response or intolerable drug side effects. Results: Of 157 CA-CDI cases, median age was 50 years and 75.3% were female. Forty percent of CA-CDI cases were subsequently hospitalized for CDI management and the remaining were treated as outpatients. On univariate analysis, patients hospitalized for CA-CDI were significantly older (median age 64 vs 44 years, p<0.001), had higher rates of severe disease (33.3% vs 11.7%, p=0.001), higher Charlson Comorbidity index scores (p=0.001) and less likely to have antibiotic exposure (68.2% vs 85.2%, p=0.01). There were no differences in sex, recent gastrointestinal endoscopy procedures, initial CDI treatment, treatment failure or risk of recurrence in those hospitalized compared to managed as an outpatient. On multivariate logistic regression analysis, increasing age (p=0.02), higher Charlson Comorbidity index (p=0.04), disease severity (p=0.02) and lack of antibiotic exposure (p=0.02) predicted the need for hospitalization in patients with CA-CDI. Conclusion: In this population-based cohort, forty percent of CA-CDI cases were hospitalized for management of CDI. Patients hospitalized were older and had more severe CDI. Interestingly, those hospitalized were less likely to have received prior antibiotics, suggesting that other undefined risk factors associated with CA-CDI were operative, and could be predictors of hospitalization. Future studies are needed to better characterize determinants of infection risk and need for hospitalization in CA-CDI. This research was supported by an industry grant from ViroPharma.

Treatment Outcome with Imatinib-Based Maintenance Therapy in Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukaemia (Ph+ALL) Ineligible for Allogeneic Stem Cell Transplantation (SCT).

Background: The tyrosine kinase inhibitor imatinib (IM), alone or in combination with induction and post-remission chemotherapy, has become the mainstay of front-line treatment for Ph+ ALL, followed by allogeneic SCT as a potentially curative treatment option. However, alloSCT is not feasible in many elderly or comorbid patients. In a prospective, randomized clinical trial of elderly patients with de novo Ph+ ALL, we recently demonstrated that IM induction followed by IM in combination with intensive consolidation chemotherapy of approximately one year duration was feasible in the majority of pts. but associated with a high relapse rate. To assess the impact of IM-based maintenance, we here provide an analysis of maintenance therapy with IM either alone, in combination with low dose interferon-α (LD-IFNα), or with zoledronic acid. In addition, we examined whether determination of minimal residual disease (MRD) and/or BCR-ABL mutation status prior to and during pre-maintenance therapy were predictive of freedom from relapse and remission duration.Patients and Methods: Remission induction and consolidation therapy have been reported previously (Ottmann et al., Cancer 109:2068–76, 2007). As the present analysis focuses entirely on the maintenance phase, patients who failed to achieve a CR, relapsed or died during the consolidation cycles are not included. Following a median of 6 cycles of remission induction and consolidation chemotherapy given concurrently with IM, 33 CR pts. (n=33; median age 69.5 yrs; [58–75 yrs.]) were enrolled either in a clinical trial of IM in combination with low-dose IFN (n=19), or with zoledronic acid (n=4), or received Glivec as a single agent (n=8). Minimal residual disease was serially assessed by quantitative RT-PCR and mutational analyses was performed by D-HPLC and direct sequencing.Results: With a median duration of maintenance of 17 months (range 6–72 mos.), 14 of 33 patients (42%) are in ongoing CR, with a median maintenance duration of 46 mos. (20–72 mos.). Median overall survival of all patients is 28 mos. (range: 9–81 mos.). Detection of a BCR-ABL mutation at or within 4 weeks of initial diagnosis was associated with inferior remission duration, 18 mos. versus 27 mos. (p=0.06). Remission was independent of the MRD response during induction and consolidation: 24 mos. and 26 mos. in pts. who did or did not achieve MRD negativity at any time; similarly, detection of MRD at the start of maintenance had no impact on time to progression.Conclusions: Among elderly Ph+ALL pts. who did not undergo SCT, treatment outcome with IM-based maintenance therapy is encouraging, but remissions are not sustained in the majority of patients. Surprisingly, persistent MRD positivity during consolidation or at the start of maintenance were not associated with an inferior outcome; conversely, relapses occurred even in patients who had achieved prolonged MRD negativity.

A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease

Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD. Fifty-five children (age, 13+/-2 years) were randomized to treatment with 6-MP (1.5 mg x kg(-1) x day(-1)) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months. Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P<0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P<0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group. Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.

Intelligence in epilepsy: a prospective study in children.

A prospective study tested the stability of the IQ in children with seizure disorders. Seventy-two children with epilepsy underwent psychological evaluations within two weeks of initial diagnosis and yearly thereafter for an average of 4 years. Forty-five of the patients also had a nonepileptic sib evaluated in parallel. The mean IQ for all the children with epilepsy was 99.7 (+/- 20.2, standard deviation) at the time of the initial test, not significantly different from the siblings. This score did not change appreciably with time. Eight of the 72 epileptic patients (11.1%), however, had a persistent decrease in IQ of 10 points or more. These patients had a higher incidence of drug levels in the toxic range (p less than 0.001), their epilepsy was more difficult to control (p less 0.005), and their seizures began at an earlier age (p less than 0.05). Discriminant analysis is revealed that the number of drugs to which the patient became toxic and the age at seizure onset were the two best predictors of ultimate IQ. These two predictors correctly classified 71% of all patients as to whether their IQ would drop by 10 or more points during the test period, remain within 10 points of the initial test score, or increase by more than 10 points. Total number of seizures and seizure control were less good predictors, according to this method of analysis. The findings suggest that, in younger children in particular, total seizure control should not be achieved at the price of repeated episodes of drug toxicity.