What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis.

Background: Our prior Systemic Treatment Options for Cancer of the Prostate systematic reviews showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (Doc), but not zoledronic acid (ZA), were added to androgen-deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (Cel) with ZA and ADT. To establish the optimal treatments, a network meta-analysis (NMA) was carried out based on aggregate data (AD) from all available studies. Methods: Overall survival (OS) and failure-free survival data from completed Systemic Treatment Options for Cancer of the Prostate reviews of Doc, ZA and AAP and from recent trials of ZA and Cel contributed to this comprehensive AD-NMA. The primary outcome was OS. Correlations between treatment comparisons within one multi-arm, multi-stage trial were estimated from control-arm event counts. Network consistency and a common heterogeneity variance were assumed. Results: We identified 10 completed trials which had closed to recruitment, and one trial in which recruitment was ongoing, as eligible for inclusion. Results are based on six trials including 6204 men (97% of men randomised in all completed trials). Network estimates of effects on OS were consistent with reported comparisons with ADT alone for AAP [hazard ration (HR) = 0.61, 95% confidence interval (CI) 0.53-0.71], Doc (HR = 0.77, 95% CI 0.68-0.87), ZA + Cel (HR = 0.78, 95% CI 0.62-0.97), ZA + Doc (HR = 0.79, 95% CI 0.66-0.94), Cel (HR = 0.94 95% CI 0.75-1.17) and ZA (HR = 0.90 95% CI 0.79-1.03). The effect of ZA + Cel is consistent with the additive effects of the individual treatments. Results suggest that AAP has the highest probability of being the most effective treatment both for OS (94% probability) and failure-free survival (100% probability). Doc was the second-best treatment of OS (35% probability). Conclusions: Uniquely, we have included all available results and appropriately accounted for inclusion of multi-arm, multi-stage trials in this AD-NMA. Our results support the use of AAP or Doc with ADT in men with metastatic hormone-naive prostate cancer. AAP appears to be the most effective treatment, but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials. To fully account for patient variability across trials, changes in prognosis or treatment effects over time and the potential impact of treatment on progression, a network meta-analysis based on individual participant data is in development.

Use of strategies to improve retention in primary care randomised trials: a qualitative study with in-depth interviews.

OBJECTIVE: To explore the strategies used to improve retention in primary care randomised trials. DESIGN: Qualitative in-depth interviews and thematic analysis. PARTICIPANTS: 29 UK primary care chief and principal investigators, trial managers and research nurses. METHODS: In-depth face-to-face interviews. RESULTS: Primary care researchers use incentive and communication strategies to improve retention in trials, but were unsure of their effect. Small monetary incentives were used to increase response to postal questionnaires. Non-monetary incentives were used although there was scepticism about the impact of these on retention. Nurses routinely used telephone communication to encourage participants to return for trial follow-up. Trial managers used first class post, shorter questionnaires and improved questionnaire designs with the aim of improving questionnaire response. Interviewees thought an open trial design could lead to biased results and were negative about using behavioural strategies to improve retention. There was consensus among the interviewees that effective communication and rapport with participants, participant altruism, respect for participant's time, flexibility of trial personnel and appointment schedules and trial information improve retention. Interviewees noted particular challenges with retention in mental health trials and those involving teenagers. CONCLUSIONS: The findings of this qualitative study have allowed us to reflect on research practice around retention and highlight a gap between such practice and current evidence. Interviewees describe acting from experience without evidence from the literature, which supports the use of small monetary incentives to improve the questionnaire response. No such evidence exists for non-monetary incentives or first class post, use of which may need reconsideration. An exploration of barriers and facilitators to retention in other research contexts may be justified.

Substantial improvement in UK cervical cancer survival with chemoradiotherapy: results of a Royal College of Radiologists' audit.

AIMS: To compare survival and late complications between patients treated with chemoradiotherapy and radiotherapy for locally advanced cervix cancer. MATERIALS AND METHODS: A Royal College of Radiologists' audit of patients treated with radiotherapy in UK cancer centres in 2001-2002. Survival, recurrence and late complications were assessed for patients grouped according to radical treatment received (radiotherapy, chemoradiotherapy, postoperative radiotherapy or chemoradiotherapy) and non-radical treatment. Late complication rates were assessed using the Franco-Italian glossary. RESULTS: Data were analysed for 1243 patients from 42 UK centres. Overall 5-year survival was 56% (any radical treatment); 44% (radical radiotherapy); 55% (chemoradiotherapy) and 71% (surgery with postoperative radiotherapy). Overall survival at 5 years was 59% (stage IB), 44% (stage IIB) and 24% (stage IIIB) for women treated with radiotherapy, and 65% (stage IB), 61% (stage IIB) and 44% (stage IIIB) for those receiving chemoradiotherapy. Cox regression showed that survival was significantly better for patients receiving chemoradiotherapy (hazard ratio=0.77, 95% confidence interval 0.60-0.98; P=0.037) compared with those receiving radiotherapy taking age, stage, pelvic node involvement and treatment delay into account. The grade 3/4 late complication rate was 8% (radiotherapy) and 10% (chemoradiotherapy). Although complications continued to develop up to 7 years after treatment for those receiving chemoradiotherapy, there was no apparent increase in overall late complications compared with radiotherapy alone when other factors were taken into account (hazard ratio=0.94, 95% confidence interval 0.71-1.245; P=0.667). DISCUSSION: The addition of chemotherapy to radiotherapy seems to have improved survival compared with radiotherapy alone for women treated in 2001-2002, without an apparent rise in late treatment complications.

Uso de transfusao de concentrados de leucocitos polimorfonucleares em sepse neonatal. / Use of transfusion of polymorphonuclear leukocytes concentrates in neonatal sepsis

Os autores relatam sua experiencia com o uso de transfusoes de concentrados de leucocitos polimorfonucleares (TPMN) em 21 casos de sepse neonatal (SNN) admitidos no bercario do Hospital de Base do Distrito Federal (HBDF), no perido de junho de 1982 a maio de 1983. Tentam fazer correlacao da incidencia da SNN com fatores perinatais e usam como indicadores laboratoriais de infeccao a bacteriologia, presenca de leucocitose ou leucopenia, morfologia dos leucocitos, relacao bastao (e formas imaturas)/neutrofilos totais e a proteina C reativa positiva. Mostram ainda os achados clinicos mais frequentes bem como os agentes bacterianos isolados no Servico.Terminam por admitir a real validade dessa nova terapia na reducao da taxa de mortalidade por SNN no bercario do HBDF, visto ter havido apenas um obito no grupo estudado