Individualized 6‐mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial

Objectives

This randomized controlled trial tested the hypothesis that children with non‐high‐risk acute lymphoblastic leukemia could benefit from individualized 6‐mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation minimal residual disease (MRD) positivity and event‐free survival.

Methods

392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6‐mercaptopurine (25 mg/m²/day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25 mg/m²/day beginning on days 50 and/or 71 unless dose‐limiting myelosuppression had occurred.

Results

In the experimental arm, 166 patients (42%) received one dose increment, and 62 (16%) received two. Fifty‐seven of 387 (15%) patients in the experimental arm were MRD positive at end of consolidation vs 77 of 389 (20%) in the control arm (P = .08). Five‐year probability of event‐free survival was 0.89 (95% CI: 0.85‐0.93) in the experimental arm vs 0.93 (0.90‐0.96) in the control arm (P = .13). The median accumulated length of 6‐mercaptopurine treatment interruptions was 7 (IQR 2‐12) in the experimental arm vs 4 (IQR 0‐10) in the control arm (P = .002).

Conclusion

This study found no benefit from individualized 6‐mercaptopurine increments compared to standard therapy.     

Starch-encapsulated chlorpyrifos: release rate,insecticidal activity and degradation in soil

Incorporation of chlorpyrifos into starch matrices was achieved by thermal gelatinization. The level of amylose content in the starch matrices (10 and 52%) and the addition of auxiliary agents, i.e. solvent, emulsifiers or both, were varied and eight different formulations were prepared. According to differential scanning calorimetry (DSC) and X-ray diffraction measurements, chlorpyrifos was partly present in a crystalline form in all the starch formulations. The formulations had controlled release properties, and the release rate into water could be described by a linear model. In a bioassay, the formulations killed all larvae of the cabbage root fly at a dosing of 1.4 kg a.i. per ha. The degradation of chlorpyrifos in soil from the starch formulations could be described in a nonlinear logistic model and the half-life was predicted to be 88 days. Differences in the amount of amylose in the starch as well as the addition of solvent and emulsifiers in the preparation procedure had no systematic influence on the release rate, the insecticidal effect and the degradation rate. No correlation between release rate into water and degradation in soil could be established. Two commercial chlorpyrifos formulations Lorsban#174; 15 G (granular) and Cyfos#174; 500 gl -1 (emulsifiable concentrate), were included in the study for comparison.     

Mental health care professionals' accounts of actions and responsibilities related to managing physical health among people with severe mental illness

Background

Life expectancy of people with severe mental illness (SMI) is greatly shortened compared to the general population, and despite extensive research, this issue is unsolved. Although it is widely recognised that people with SMI need support from health care services to manage health related issues, profound health inequalities exist within provision of health care. The aim of this study was to examine how mental health care professionals accounted for their actions and responsibilities related to managing physical health issues among people with SMI.

Predictive value of combined analysis of pro‐NPY and ERG in localized prostate cancer

This study aimed to investigate if combined analysis of pro‐Neuropeptide Y (NPY) and ERG expression in tumor tissue are associated with biochemical failure (BF), castration‐based treatment, castration‐resistant prostate cancer (CRPC), and prostate cancer (PCa)‐specific death for men undergoing radical prostatectomy (RP) for PCa. This study included 315 patients, who underwent RP from 2002 to 2005. Both pro‐NPY and ERG expression were analyzed using immunohistochemistry and were scored as low or high and negative or positive, respectively. Risk of BF, castration‐based treatment, CRPC, and PCa‐specific death were analyzed with multiple cause‐specific Cox regression analyses and stratified cumulative incidences using competing risk assessment. Median follow‐up was 13.0 years (95% CI: 12.7–13.2). In total, 85.7% were pro‐NPY high and 14.3% were pro‐NPY low. The combined analyses of pro‐NPY and ERG expression was not associated with risk of BF (p = 0.7), castration‐based treatment (p = 0.8), CRPC (p = 0.4) or PCa‐specific death (p = 0.5). In the multiple cause‐specific Cox regression analysis, pro‐NPY high and ERG positivity was not associated with BF (HR: 1.02; 95% CI 0.6–1.7; p = 0.94). In conclusion the combination of pro‐NPY and ERG expression did not show association with risk of BF, castration‐based treatment, CRPC, and PCa‐specific death following RP.     

Communication skills training for health care professionals improves the adult orthopaedic patient’s experience of quality of care

Rationale: Despite the fact that communication has become a core topic in health care, patients still experience the information provided as insufficient or incorrect and a lack of involvement. Objective: To investigate whether adult orthopaedic patients’ evaluation of the quality of care had improved after a communication skills training course for healthcare professionals. Design and methods: The study was designed as an intervention study offering professionals training in communicating with patients and colleagues. The outcome was measured by assessing patients’ experience of quality of care. Data were collected by means of a questionnaire and analysed using a linear regression model. Approval was obtained from the Danish Data Protection Agency. Results: A total of 3133 patients answered the questionnaire, 1279 before staff had attended courses and 1854 in the postcourse period, with response rates of 67.8 and 77.8%, respectively. After the course period, significant increases in responses indicating ‘considerable’ improvement were recorded for 15/19 questions, nonsignificant increases were registered for 3/19 questions and a statistically significant decrease for one question. Study limitations: This being an effectiveness study, it is deemed that the organizational changes taking place during the study period constitute no serious limitation. Response rates were comparable to those of other studies. Conclusion: Patients show increased satisfaction with the quality of health care after professionals have attended a communication skills training course, even when implemented in an entire department. Practice implications: We recommend that healthcare professionals are trained in patient‐centred communication and that training is extended to the entire organization.     

ALIS‐FLP: Amplified ligation selected fragment‐length polymorphism method for microbial genotyping

A DNA fingerprinting method known as ALIS‐FLP (amplified ligation selected fragment‐length polymorphism) has been developed for selective and specific amplification of restriction fragments from TspRI restriction endonuclease digested genomic DNA. The method is similar to AFLP, but differs in that only one specific restriction enzyme (TspRI) is used. The cohesive ends of the DNA fragments are ligated with two types of oligonucleotide. A long oligonucleotide containing the primer site and the specific 9 nt 3 prime end, which is complementary to specific 9 nt, cohesive 3 prime end of the TspRI genomic DNA fragment, and a short, degenerated, oligonucleotide covering the remaining TspRI cohesive ends. Other cohesive ends are covered by a short degenerated oligonucleotide lacking the primer site. The ligation mixture is used as a template for amplification using a single primer corresponding to the 5 prime end of the long, specific oligonucleotide. The selection of TspRI digested genomic DNA fragments for amplification is achieved by sequence selective ligation of the specific long oligonucleotide carrying the primer site to both ends of the specific target fragment. This technique allows for differentiation of the organisms without previous knowledge of their DNA sequence. The usefulness of the method is confirmed by genotyping of 70 previously characterized clinical E. coli isolates. The grouping obtained was identical to the results of REA‐PFGE. Versatility of the method is highlighted, i.e. its combining the advantages of the AFLP technique with a simple, rapid and cheap polymerase chain reaction product detection method.     

Reliability of Infrared Thermometric Measurements of Skin Temperature in the Hand

Study DesignClinical measurement study.IntroductionSkin temperature asymmetries (STAs) are used in the diagnosis of complex regional pain syndrome (CRPS), but little evidence exists for reliability of the equipment and methods.PurposeThis study examined the reliability of an inexpensive infrared (IR) thermometer and measurement points in the hand for the study of STA.MethodsST was measured three times at five points on both hands with an IR thermometer by two raters in 20 volunteers (12 normals and 8 CRPS).ResultsST measurement results using IR thermometers support inter-rater reliability: intraclass correlation coefficient (ICC) estimate for single measures 0.80; all ST measurement points were also highly reliable (ICC single measures, 0.83–0.91).ConclusionsThe equipment demonstrated excellent reliability, with little difference in the reliability of the five measurement sites. These preliminary findings support their use in future CRPS research.Level of EvidenceNot applicable.