Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO

A prospective, multicenter, randomized trial was undertaken to compare the efficacy and toxicity of adriamycin with mitoxantrone within a 6-drug combination chemotherapy regimen for elderly patients (older than 60 years) with high-grade non-Hodgkin lymphoma (HGL) given for a minimum of 8 weeks. A total of 516 previously untreated patients aged older than 60 years were randomized to receive 1 of 2 anthracycline-containing regimens: adriamycin, 35 mg/m2 intravenously (IV) on day 1 (n = 259), or mitoxantrone, 7 mg/m2 IV on day 1 (n = 257); with prednisolone, 50 mg orally on days 1 to 14; cyclophosphamide, 300 mg/m2 IV on day 1; etoposide, 150 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 8; and bleomycin, 10 mg/m2 IV on day 8. Each 2-week cycle was administered for a minimum of 8 weeks in the absence of progression. Forty-three patients were ineligible for analysis. The overall and complete remission rates were 78% and 60% for patients receiving PMitCEBO and 69% and 52% for patients receiving PAdriaCEBO (P = .05, P = .12, respectively). Overall survival was significantly better with PMitCEBO than PAdriaCEBO (P = .0067). However, relapse-free survival was not significantly different (P = .16). At 4 years, 28% of PAdriaCEBO patients and 50% of PMitCEBO patients were alive (P = .0001). Ann Arbor stage III/IV, World Health Organization performance status 2-4, and elevated lactate dehydrogenase negatively influenced overall survival from diagnosis. In conclusion, the PMitCEBO 8-week combination chemotherapy regimen offers high response rates, durable remissions, and acceptable toxicity in elderly patients with HGL

Public acceptability of financial incentives for smoking cessation in pregnancy and breastfeeding

Objective To survey public attitudes about incentives for smoking cessation in pregnancy and for breast feeding to inform trial design. Design Cross-sectional survey. Setting and participants British general public. Methods Seven promising incentive strategies had been identified from evidence syntheses and qualitative interview data from service users and providers. These were shopping vouchers for: (1) validated smoking cessation in pregnancy and (2) after birth; (3) for a smoke-free home; (4) for proven breast feeding; (5) a free breast pump; (6) payments to health services for reaching smoking cessation in pregnancy targets and (7) breastfeeding targets. Ipsos MORI used area quota sampling and home-administered computer-assisted questionnaires, with randomised question order to assess agreement with different incentives (measured on a five-point scale). Demographic data and target behaviour experience were recorded. Analysis used multivariable ordered logit models. Results Agreement with incentives was mixed (ranging from 34% to 46%) among a representative sample of 1144 British adults. Mean agreement score was highest for a free breast pump, and lowest for incentives for smoking abstinence after birth. More women disagreed with shopping vouchers than men. Those with lower levels of education disagreed more with smoking cessation incentives and a breast pump. Those aged 44 or under agreed more with all incentive strategies compared with those aged 65 and over, particularly provider targets for smoking cessation. Non-white ethnic groups agreed particularly with breastfeeding incentives. Current smokers with previous stop attempts and respondents who had breast fed children agreed with providing vouchers for the respective behaviours. Up to £40/month vouchers for behaviour change were acceptable (>85%). Conclusions Women and the less educated were more likely to disagree, but men and women of childbearing age to agree, with incentives designed for their benefit. Trials evaluating reach, impact on health inequalities and ethnic groups are required prior to implementing incentive interventions

Perspectives on financial incentives to health service providers for increasing breast feeding and smoking quit rates during pregnancy: a mixed methods study

Objective: To explore the acceptability, mechanisms and consequences of provider incentives for smoking cessation and breast feeding as part of the Benefits of Incentives for Breastfeeding and Smoking cessation in pregnancy (BIBS) study. Design: Cross-sectional survey and qualitative interviews. Setting: Scotland and North West England. Participants: Early years professionals: 497 survey respondents included 156 doctors; 197 health visitors/maternity staff; 144 other health staff. Qualitative interviews or focus groups were conducted with 68 pregnant/postnatal women/family members; 32 service providers; 22 experts/decision-makers; 63 conference attendees. Methods: Early years professionals were surveyed via email about the acceptability of payments to local health services for reaching smoking cessation in pregnancy and breastfeeding targets. Agreement was measured on a 5-point scale using multivariable ordered logit models. A framework approach was used to analyse free-text survey responses and qualitative data. Results: Health professional net agreement for provider incentives for smoking cessation targets was 52.9% (263/497); net disagreement was 28.6% (142/497). Health visitors/maternity staff were more likely than doctors to agree: OR 2.35 (95% CI 1.51 to 3.64; p<0.001). Net agreement for provider incentives for breastfeeding targets was 44.1% (219/497) and net disagreement was 38.6% (192/497). Agreement was more likely for women (compared with men): OR 1.81 (1.09 to 3.00; p=0.023) and health visitors/maternity staff (compared with doctors): OR 2.54 (95% CI 1.65 to 3.91; p<0.001). Key emergent themes were 'moral tensions around acceptability', 'need for incentives', 'goals', 'collective or divisive action' and 'monitoring and proof'. While provider incentives can focus action and resources, tensions around the impact on relationships raised concerns. Pressure, burden of proof, gaming, box-ticking bureaucracies and health inequalities were counterbalances to potential benefits. Conclusions: Provider incentives are favoured by non-medical staff. Solutions which increase trust and collaboration towards shared goals, without negatively impacting on relationships or increasing bureaucracy are required

Applying psychological theory to evidence-based clinical practice : identifying factors predictive of managing upper respiratory tract infections without antibiotics

Background: Psychological models can be used to understand and predict behaviour in a wide range of settings. However, they have not been consistently applied to health professional behaviours, and the contribution of differing theories is not clear. The aim of this study was to explore the usefulness of a range of psychological theories to predict health professional behaviour relating to management of upper respiratory tract infections (URTIs) without antibiotics. Methods: Psychological measures were collected by postal questionnaire survey from a random sample of general practitioners (GPs) in Scotland. The outcome measures were clinical behaviour (using antibiotic prescription rates as a proxy indicator), behavioural simulation (scenario-based decisions to managing URTI with or without antibiotics) and behavioural intention (general intention to managing URTI without antibiotics). Explanatory variables were the constructs within the following theories: Theory of Planned Behaviour (TPB), Social Cognitive Theory (SCT), Common Sense Self-Regulation Model (CS-SRM), Operant Learning Theory (OLT), Implementation Intention (II), Stage Model (SM), and knowledge (a non-theoretical construct). For each outcome measure, multiple regression analysis was used to examine the predictive value of each theoretical model individually. Following this 'theory level' analysis, a 'cross theory' analysis was conducted to investigate the combined predictive value of all significant individual constructs across theories. Results: All theories were tested, but only significant results are presented. When predicting behaviour, at the theory level, OLT explained 6% of the variance and, in a cross theory analysis, OLT 'evidence of habitual behaviour' also explained 6%. When predicting behavioural simulation, at the theory level, the proportion of variance explained was: TPB, 31%; SCT, 26%; II, 6%; OLT, 24%. GPs who reported having already decided to change their management to try to avoid the use of antibiotics made significantly fewer scenario-based decisions to prescribe. In the cross theory analysis, perceived behavioural control (TPB), evidence of habitual behaviour (OLT), CS-SRM cause (chance/bad luck), and intention entered the equation, together explaining 36% of the variance. When predicting intention, at the theory level, the proportion of variance explained was: TPB, 30%; SCT, 29%; CS-SRM 27%; OLT, 43%. GPs who reported that they had already decided to change their management to try to avoid the use of antibiotics had a significantly higher intention to manage URTIs without prescribing antibiotics. In the cross theory analysis, OLT evidence of habitual behaviour, TPB attitudes, risk perception, CS-SRM control by doctor, TPB perceived behavioural control and CS-SRM control by treatment entered the equation, together explaining 49% of the variance in intention. Cnclusion: The study provides evidence that psychological models can be useful in understanding and predicting clinical behaviour. Taking a theory-based approach enables the reation of a replicable methodology for identifying factors that predict clinical behaviour. Hwever, a number of conceptual and methodological challenges remain

Neurotropic viruses and cerebral palsy: population based case-control study

Objective: To investigate the association between cerebral palsy and direct evidence for perinatal exposure to neurotropic viruses. Design: Population based case-control study. Setting: Adelaide Women's and Children's Hospital Research Laboratory. Participants and main outcome measures: Newborn screening cards of 443 white case patients with cerebral palsy and 883 white controls were tested for viral nucleic acids from enteroviruses and herpes viruses by using polymerase chain reaction. Herpes group A viruses included herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 8 (HHV-8), and herpes group B viruses included varicella zoster virus (VZV) and human herpes viruses 6 and 7 (HHV-6 and HHV-7). Results: The prevalence of viral nucleic acids in the control population was high: 39.8% of controls tested positive, and the prevalence was highest in preterm babies. The detection of herpes group B viral nucleic acids increased the risk of developing cerebral palsy (odds ratio 1.68, 95% confidence interval 1.09 to 2.59). Conclusions: Perinatal exposure to neurotropic viruses is associated with preterm delivery and cerebral palsy.Catherine S. Gibson, Alastair H. MacLennan, Paul N. Goldwater, Eric A. Haan, Kevin Priest and Gustaaf A. Dekker

Seminars may increase recruitment to randomised controlled trials: lessons learned from WISDOM

Background: Recruiting patients to large randomised controlled trials (RCTs) in the primary care setting can be challenging. Research teams need to identify and utilise strategies that both maximise the efficiency of recruitment and minimise the burden on general practitioners. Purpose: To describe our methods for identifying, approaching and recruiting female patients aged 50–69 years to a long-term double-blind RCT of hormone therapy (HT) – the Women's International Study of long Duration Oestrogen after Menopause (WISDOM). The effectiveness of conducting group seminars with patients prior to one-to-one screening is discussed. Methods: Female patients aged between 50 and 69 years were sent letters from participating general practitioners in Adelaide inviting them to participate in WISDOM and attend an initial seminar providing information about HT and the trial prior to a screening interview with a trial nurse. Recruitment rates for those who did or did not attend group seminars were compared. Results: Women who attended a group seminar conducted by the research team were twice as likely to attend an initial screening visit and enrol to participate in WISDOM than women who did not attend a seminar (p &lt; 0.001). In addition, it was estimated that the time required to randomise a woman in the trial, and the number and duration of telephone calls to screen out uninterested women, was reduced for the seminar group. Conclusion: Conducting group seminars with potential participants may be a useful strategy for maximising recruitment from general practice, by increasing patient information and reducing a research team's workload.Bronwen J. Paine, Nigel P. Stocks and Alastair H. MacLenna

Effects of present-day deglaciation in Iceland on mantle melt production rates

Ongoing deglaciation in Iceland not only causes uplift at the surface but also increases magma production at depth due to decompression of the mantle. Here we study glacially induced decompression melting using 3‐D models of glacial isostatic adjustment in Iceland since 1890. We find that the mean glacially induced pressure rate of change in the mantle increases melt production rates by 100–135%, or an additional 0.21–0.23 km3 of magma per year beneath Iceland. Approximately 50% of this melt is produced underneath central Iceland. The greatest volumetric increase is found directly beneath Iceland's largest ice cap, Vatnajökull, colocated with the most productive volcanoes. Our models of the effect of deglaciation on mantle melting predict a significantly larger volumetric response than previous models which only considered the effect of deglaciation of Vatnajökull, and only mantle melting directly below Vatnajökull. Although the ongoing deglaciation significantly increases the melt production rate, the increase in melt supply rate at the base of the lithosphere is delayed and depends on the melt ascent velocity through the mantle. Assuming that 25% of the melt reaches the surface, the upper limit on our deglaciation‐induced melt estimates for central Iceland would be equivalent to an eruption the size of the 2010 Eyjafjallajökull summit eruption every seventh year

Structures and orientational transitions in thin films of tilted hexatic smectics

We present detailed systematic studies of structural transformations in thin liquid crystal films with the smectic-C to hexatic phase transition. For the first time all possible structures reported in the literature are observed for one material (5 O.6) at the variation of temperature and thickness. In unusual modulated structures the equilibrium period of stripes is twice with respect to the domain size. We interpret these patterns in the frame work of phenomenological Landau type theory, as equilibrium phenomena produced by a natural geometric frustration in a system having spontaneous splay distortion.Comment: 7 pages, 6 figure

Front propagation into unstable and metastable states in Smectic C* liquid crystals: linear and nonlinear marginal stability analysis

We discuss the front propagation in ferroelectric chiral smectics (SmC*) subjected to electric and magnetic fields applied parallel to smectic layers. The reversal of the electric field induces the motion of domain walls or fronts that propagate into either an unstable or a metastable state. In both regimes, the front velocity is calculated exactly. Depending on the field, the speed of a front propagating into the unstable state is given either by the so-called linear marginal stability velocity or by the nonlinear marginal stability expression. The cross-over between these two regimes can be tuned by a magnetic field. The influence of initial conditions on the velocity selection problem can also be studied in such experiments. SmC$^*$ therefore offers a unique opportunity to study different aspects of front propagation in an experimental system