Predicting primary treatment failure using interim FDG-PET scanning in diffuse large B-cell lymphoma.

Interim FDG-PET (iPET) in diffuse large B-cell lymphoma (DLBCL) is increasingly practised and used in clinical trials to adapt further therapy. However, the optimum timing and methodology of iPET remains controversial. We retrospectively analysed the iPET results and outcomes of 200 DLBCL patients where FDG-PET was routinely performed at baseline, after 2 cycles (iPET2) and at completion of chemoimmunotherapy. iPET was also performed after 4 cycles (iPET4) where at iPET2, Deauville score (DS) was ≥4. Scans were assessed by blinded expert lymphoma PET physicians for DS, maximum standard uptake value (SUVmax), total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG). Treatment failure was defined as death, progression or refractory disease. 95.5% of patients received R-CHOP. No baseline PET parameter was predicted for EFS or OS independent of the NCCN-IPI. The multivariable analysis at iPET2 showed DS5 (19.5% of cases) predicted treatment failure (HR 6.29, 95% CI 3.01-13.17, P < .001), but DS4 was equivalent to DS1-3. At iPET4, ΔSUVmax < 66% predicted treatment failure (HR 5.49, 95% CI 3.03-9.99, P < .001). By multivariable analysis of all time points, high NCCN-IPI and DS5 at iPET2 were negative predictors of survival. These findings were independent of novel prognostic markers.

Outpatient Medication Use in Chinese Geriatric Patients Admitted for Falls: A Case-Control Study at an Acute Hospital in Hong Kong.

The study objective was to investigate the association of polypharmacy and medications with patient falls resulting in hip fractures among community-living geriatric patients. A case-control study was conducted at an acute public hospital in Hong Kong. The study population was community-living Chinese patients aged 65 years and above who were admitted for falls resulting in hip fractures during an 18-month study period. Each of these patients was matched to a control patient with the same age and sex, but without falls and fractures. Data were collected from electronic patient record. Data of 170 cases and 170 controls were eventually collected. The following variables associated with increased risk of falls resulting in hip fractures remained statistically significant after multivariate logistic regression, including benign prostatic hyperplasia [odds ratio (OR) = 2.654; 95% confidence interval (CI), 1.105-6.378; P = 0.029], first-generation antihistamines (OR = 3.176; 95% CI, 1.044-9.664; P = 0.042), antiparkinson medications (OR = 3.754; 95% CI, 1.158-12.169; P = 0.027), osteoporosis (OR = 3.159; 95% CI, 1.167-8.552; P = 0.024), and use of walking aids (OR = 2.543; 95% CI, 1.544-4.188; P < 0.001). In conclusion, this study identified various medications and comorbidities, rather than polypharmacy based on the number of medications, as predictors associated with increased risk of falls resulting in hip fractures for local geriatric patients. The findings provided insights into the potential medication-related fall prevention strategies, including clinical medication review, adverse drug event monitoring, and drug optimization.

Acute respiratory distress syndrome precipitated by granulocyte colony-stimulating factor in undiagnosed Pneumocystis jirovecii pneumonia.

We present the case of a 62-year-old man with rheumatoid arthritis who developed a leukaemoid reaction and acute respiratory distress syndrome (ARDS) following granulocyte colony-stimulating factor (G-CSF) administration that had been given to treat neutropenia secondary to methotrexate and leflunomide toxicity. Later it was established that he had Pneumocystis jirovecii pneumonia, which was treated to complete resolution with a course of corticosteroids and antibiotics. This case highlights the potential risk of G-CSF administration in an immune compromised individual in the midst of bone marrow recovery in the context of active infection. Recognition of immune escape syndromes is vital and requires an understanding of potential triggers and risk factors.

Transmission of hepatitis B virus (genotype E) in a haemodialysis unit.

BACKGROUND: The Rosenheim report, published in 1972, was aimed at decreasing the transmission of hepatitis B virus (HBV) in the renal unit. A review in 1996, revealed the non-compliance of some centres with the guidance to vaccinate individuals against HBV. OBJECTIVES: To describe two events of acute hepatitis B virus (HBV) infection within 9 weeks in individuals attending the renal unit and the steps taken to prevent further transmission. STUDY DESIGN: Serological and molecular testing was carried out on the two individuals with acute HBV and other HBV carriers in the unit. Epidemiological information was collected along with information on HBV vaccination and HBsAg screening. RESULTS: There were 15 known HBV carriers in the unit. HBV genotype E was transmitted from a carrier to patient 1 when they were in the same ward. Transmission to patient 2 occurred when he followed patient 1 on the theatre list. Breaks in infection control were identified and steps were taken to prevent further transmission events. CONCLUSIONS: Breaks in infection control procedures were rectified. No further transmission of HBV was identified. This highlights the need for vigilance regarding infection control practices in the renal unit setting.

Procedures that assess inconsistency in meta-analyses can assess the likelihood of response bias in multiwave surveys.

BACKGROUND AND OBJECTIVE: Response bias may affect the result of surveys with <100% response rate. We applied methods commonly used in meta-analysis to ascertain the extent to which response bias affects multiwave survey results. METHODS: To test hypotheses of between-wave similarity, we used the Cochran-Armitage test for trends and the Q-test of heterogeneity across waves in a survey of 2,127 North American clinicians using six e-mail waves and one fax wave and achieving a response rate of 22%. We used the I2 statistic To quantify the extent of inconsistency in survey outcomes across waves not due to within-wave random error (i.e., inconsistency due to response bias). RESULTS: With this survey, tests of heterogeneity and trend were not significant and I2 equaled 0%. These results suggest that the underlying responses did not differ across waves and thus strengthened the inference that response bias was not affecting the interpretation of the survey. CONCLUSION: Researchers can use procedures that assess inconsistency in meta-analyses to evaluate the validity of a multiwave survey with a less than optimal response rate.

Randomized trials stopped early for benefit: a systematic review.

CONTEXT: Randomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown. OBJECTIVE: To evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit. DATA SOURCES: Systematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit. STUDY SELECTION: Randomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria. DATA EXTRACTION: Twelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping. DATA SYNTHESIS: Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73). CONCLUSIONS: RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.

Telecare for patients with type 1 diabetes and inadequate glycemic control: a randomized controlled trial and meta-analysis.

OBJECTIVE: To determine the efficacy of telecare (modem transmission of glucometer data and clinician feedback) to support intensive insulin therapy in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS: Thirty-one patients with type 1 diabetes on intensive insulin therapy and with HbA1c >7.8% were randomized to telecare (glucometer transmission with feedback) or control (glucometer transmission without feedback) for 6 months. The primary end point was 6-month HbA1c. To place our findings in context, we pooled HbA1c change from baseline reported in randomized trials of telecare identified in a systematic review of the literature. RESULTS: Compared with the control group, telecare patients had a significantly lower 6-month HbA1c (8.2 vs. 7.8%, P = 0.03, after accounting for HbA1c at baseline) and a nonsignificant fourfold greater chance of achieving 6-month HbA1c < or =7% (29 vs. 7%; risk difference 21.9%, 95% CI -4.7 to 50.5). Nurses spent 50 more min/patient giving feedback on the phone with telecare patients than with control patients. Meta-analysis of seven randomized trials of adult patients with type 1 diabetes found a 0.4% difference (95% CI 0-0.8) in HbA1c mean change from baseline between the telecare and control groups. CONCLUSIONS: Telecare is associated with small effects on glycemic control in patients with type 1 diabetes on intensive insulin therapy but with inadequate glycemic control.

Rituximab is associated with improved survival for aggressive B cell CNS lymphoma.

BACKGROUND: The optimal treatment strategy in patients with aggressive B cell central nervous system lymphoma suitable to receive intensive therapy is unknown. The benefit of incorporating rituximab in systemic therapy remains unclear. We performed a retrospective study examining the impact of rituximab in the context of concomitant therapies, including methotrexate, cytarabine, and radiotherapy, in patients treated with curative intent at 4 university teaching hospitals during 1996-2011. METHODS: A retrospective study of CNS lymphoma cases treated at the participating institutions was performed in accordance with institutional ethical guidelines. Patients were included if they received a diagnosis of primary diffuse large B cell lymphoma of the CNS, were HIV negative, and were treated with curative intent. RESULTS: One hundred twenty patients aged 21-81 years were identified. Rituximab recipients and nonrecipients were similar, except for rituximab recipients being more likely to have received a diagnosis after 2004. The median follow-up of surviving patients was 30 months. The 5-year overall survival was 46%. Univariate analysis revealed age ≤60 years, ECOG performance status ≤1, normal lactate dehydrogenase, diagnosis after 2004, and treatment with cytarabine and rituximab as predictive of favorable overall survival. Multivariate analysis identified age to be an independent predictor of overall survival, with a trend toward improved survival from the other variables that were significant in univariate analyses. CONCLUSIONS: In this retrospective analysis, the addition of rituximab to high-dose methotrexate-based chemotherapy in patients with aggressive B cell CNS lymphoma was associated with improved overall survival. Further studies are underway to prospectively validate these findings.

Can contraindications compromise evidence-based, patient-centered clinical practice?

BACKGROUND: Despite their often weak evidence base, contraindications convey the unequivocally adverse risk-benefit profile of an intervention in a specific clinical context. However, some patients in that context may nonetheless prefer the contraindicated intervention (with its potential benefits and risks) to the available alternatives. The impact of contraindications on treatment decisions remains unexplored. OBJECTIVE: To provide an estimate of the impact of the "contraindication" label on treatment decisions. METHODS: We conducted an international 6-wave email/internet and fax survey of practicing clinicians who were members of the American Diabetes Association or the College of Physicians and Surgeons of Ontario and had available email addresses and fax numbers. Each participant considered one of two patient scenarios. In each scenario, the patient expressed a strong preference for use of a medication that carried a "contraindication" label despite weak evidence of harm. We designed these scenarios so that respondents who placed greater weight on patient preferences and research evidence than on the label "contraindication" would be ready to prescribe the contraindicated medication. We determined the frequency with which the label "contraindication" dominated participants' treatment decisions despite patient preferences and weak evidence of harm. RESULTS: 466 participants responded (22% response rate). Depending on the group and scenario, contraindications dominated the decisions of 47% to 89% of surveyed clinicians, superseding patient preferences and research evidence. CONCLUSIONS: The label "contraindication" may often dominate clinicians' decisions about treatment and may compromise evidence-based, patient-centered clinical practice. Further research should elucidate the process that leads to the formulation of contraindications and its impact on treatment decision-making.