Results of a phase II multicenter trial of pentostatin and rituximab in patients with low grade B-cell non-Hodgkin's lymphoma: an effective and minimally toxic regimen

This study explored the efficacy and toxicity of the combination of pentostatin and rituximab, effective single agents in low-grade non-Hodgkin's lymphoma (NHL). Sixty patients with previously treated low-grade NHL were enrolled. Except for day 1, both drugs were administered weekly for 4 weeks, with week 5 off. During week 1 (day 1) only rituximab was given; subsequent weekly treatments included both drugs. Patients received a minimum of 2 five-week cycles in order to be evaluable for efficacy. Responses were evaluated on week 5 of cycle 2. If partial response (PR) or stable disease (SD) responses were noted, 2 additional cycles were administered. Final evaluations were done on week 5 of cycle 4. Of 60 patients, 58.3% had an Eastern Cooperative Oncology Group performance status (PS) of 0, and 41.7% had PS of 1; 31.7% and 51.7% had stage III or stage IV disease, respectively. Histology included follicular center, follicular, grade I (45%), II (21.7%), III (1.7%), and small lymphocytic (31.7%). Seventeen patients had prior chemotherapy, but no patients had received prior pentostatin or rituximab. Median age was 60.3 years (range, 32.5-84.7 years). Among 57 evaluable patients, 77% responded (22.3% complete response [CR], 3.5% unconfirmed CR, 35.1% PR, and 10.5% unconfirmed PR); 19.3% had SD, and 8.8% progressive disease (PD). Response rate among previously untreated patients was 83% versus 63% in previously treated patients. Median duration of response was 11 months (range, 2.3-22.2 months); median time to progression was 15 months (range, < 1-25 months). Neutropenia was the only adverse event experienced by >/= 10% of patients. Six deaths were caused by PD, and one death each was caused by acute respiratory distress, possibly related respiratory failure, and cardiac toxicity. These results suggest the combination of pentostatin/rituximab is well tolerated and active in low-grade lymphoma.     

Study of the Impact of Deltamethrin Impregnated Mosquito Nets on Malaria Incidence at a Military Station

Deltamethrin impregnated mosquito nets have been successfully used all over the world to combat malaria. To study the efficacy of these mosquito nets in the service conditions of Armed Forces, a field trial of Deltamethrin impregnated mosquito nets was carried out at Military Stations ‘A’ (trial station) and B (control station) between July 96 to June 99. July 96-June 97 was the pretrial year during which base line data was collected for malaria incidence. Three rounds of Deltamethrin impregnation of the mosquito nets were done in the trial station for the actual trial duration (July 97-June 99) in lieu of residual spraying. Antimalaria measures including residual spray were continued as usual in the control station. The intervention led to a significant decline in slide positivity rate and malaria incidence in the trial station. Malaria cases declined by 87% in the trial station whereas the control station noticed an increase by 75% at the end of the trial.Key Words: Deltamethrin impregnated mosquito nets, Malaria control     

What are appropriate rates of invasive procedures following acute myocardial infarction? A systematic review

OBJECTIVE: To assess the evidence that higher rates of coronary angiography (CA) and revascularisation (RV) in the subacute phase of acute myocardial infarction (AMI) improve patient outcomes. DATA SOURCES: MEDLINE 1990 - December 1999, Current Contents 1990-1999, Cochrane Library (Issue 4, 1999), HealthSTAR 1990-1999, selected websites and bibliographies of retrieved articles. STUDY SELECTION AND DATA EXTRACTION: Studies selected were (1) randomised trials comparing outcomes of "invasive" versus "conservative" use of CA and RV following AMI; (2) observational studies with formal methods comparing outcomes of high versus low rates of use of these procedures; and (3) clinical practice guidelines (CPGs), expert panel statements and decision analyses which met critical appraisal criteria, and which specified procedural indications. Outcome measures were rates of mortality, re-infarction and limiting or unstable angina. DATA SYNTHESIS: 56 articles were identified; 24 met inclusion criteria. Pooled data from nine RCTs of "invasive" (CA rate 96%; RV rate 66%) versus "conservative" (CA rate 28%; RV rate 19%) strategies showed no significant differences in mortality or re-infarction rates. Pooled results from 12 observational studies showed no mortality differences, but an excess reinfarction rate (8.0% vs 6.4%; P<0.001) in high- versus low-rate populations. Evidence of survival benefit from procedural intervention was strongest for patients with recurrent ischaemia combined with left ventricular dysfunction. CONCLUSIONS: In the subacute phase of AMI, rates of CA and RV in excess of 30% and 20%, respectively, may not confer additional benefit in preventing death or re-infarction. However, variability between studies in design, patient selection, and extent of cross-over from medical to procedural groups, as well as limited data on symptom status, limits generalisability of results.     

Portfolio assessment in medical students' final examinations

The introduction of an outcome-based approach to education at Dundee Medical School in Scotland instigated a search for assessment methods that would appropriately assess the students' achievements in terms of the learning outcomes. Portfolio assessment has been developed for this purpose and has been adopted for the summative assessment of students in their final examination in Dundee. The contents of the portfolio and the assessment process have been defined and the first cohort of students to be assessed in this way has been studied. The evaluation of the approach demonstrated strong staff support. Students were also positive although with some reservations. It is concluded that portfolio assessment is a powerful approach to assessing a range of curriculum outcomes not easily assessed by other methods and is worthy of inclusion in the assessor's toolkit.     

Polymorphisms in glutathione S-transferases are associated with altered risk of nonmelanoma skin cancer in renal transplant recipients: a preliminary analysis

Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity and mortality among renal transplant recipients, with tumors behaving more aggressively than those in nontransplant patients. Not all immunosuppressed patients develop NMSC, however, and in those that do, the rate of accrual and numbers of lesions vary considerably. Though ultraviolet light is critical, it is unlikely that this alone explains the observed phenotypic diversity, suggesting the possible involvement of genetic factors. Furthermore, although twin studies in nontransplant patients with NMSC suggest a low genetic component, several genes associated with susceptibility and outcome in these patients have been identified. Thus, having previously shown that polymorphism in members of the glutathione S-transferase (GST) supergene family is associated with altered NMSC risk in nontransplant patients, we examined allelism in GSTM1, GSTP1, GSTM3, and GSTT1 in 183 renal transplant recipients. GSTM1 null was associated with increased squamous cell carcinoma (SCC) risk (p = 0.042, OR = 3.1). This remained significant after correction for age, gender, and ultraviolet light exposure (p = 0.012, OR = 8.4) and was particularly strong in patients with higher ultraviolet light exposure (e.g., sunbathing score > 3, p = 0.003, OR = 11.5) and in smokers (p = 0.021, OR = 4.8). Analysis of the interaction between GSTM1 null and sunbathing score showed that the two factors were synergistic and individuals with both risk parameters demonstrated a shorter time from transplantation to development of the first SCC (p = 0.012, hazard ratio = 7.1). GSTP1*Ile homozygotes developed larger numbers of SCC (p = 0.002, rate ratio = 7.6), particularly those with lower ultraviolet light exposure and cigarette consumption. GSTM3 and GSTT1 also demonstrated significant associations, though some genotype frequencies were low. These preliminary data suggest that genetic factors mediating protection against oxidative stress are important in NMSC development in immunosuppressed patients and may be useful in identifying high-risk individuals.     

Treatment of localized carcinoma of the penis: a survey of current practice in the UK

Consensus opinion from published reports on the management of localized carcinoma of the penis recommends that patients with small, distal, non-poorly differentiated lesions should be offered penis-conserving treatment, while those with larger or more advanced lesions should be considered for amputative surgery. A questionnaire survey was sent to 289 urologists and 237 oncologists in the UK to assess their practice for the treatment of localized carcinoma of the penis. Consultants were asked to choose between penis-conserving surgery, amputation or radiotherapy as their preferred treatment for four examples of localized disease. Oncologists were also asked to indicate their preferred radiation modality (external beam radiotherapy or brachytherapy). For treating a small lesion situated distally on the glans penis, 56.7% of urologists and 94.5% of oncologists preferred penis-conserving methods; 28.8% of urologists and one oncologist preferred partial or total amputation. In total, 43.2% of urologists would consider amputative surgery for this lesion compared with only 5.5% of oncologists. Only 23.3% of oncologists considered using brachytherapy. For a 4 cm lesion situated distally, the majority of urologists surveyed (82.0%) preferred amputative surgery, while the majority of oncologists (68.5%) preferred conservative treatment. For a 1.5 cm lesion extending on to the penile shaft, 68.5% of urologists preferred amputative surgery while 85.0% of oncologists preferred penis-conserving options. For a 4 cm lesion extending on to the shaft, the vast majority of urologists (86.5%) preferred amputation as treatment compared with only 36.9% of oncologists. The results of the survey suggested that clinicians tended to favour the treatment modality of which they have most experience. As such, urologists tended to prefer surgery while clinical oncologists tended to prefer radiotherapy, irrespective of the size and position of the primary tumour or consensus opinion. These results emphasize the importance of multidisciplinary clinics and site specialization, so that both clinicians and patients can make informed choices about optimal treatment, based on the knowledge of all available treatment options.