Adherence therapy for people with Parkinson's disease

Introduction: Medication non-adherence is prevalent in Parkinson’s disease (PD). However, factors associated with non-adherence are unknown. Despite interventions to improve medication adherence being investigated in long-term conditions, few studies have focused on PD. Adherence Therapy (AT) is a novel, patient-centred approach to maximising adherence that has shown benefit in other chronic conditions. Aim: To investigate the efficacy of AT for improving medication adherence and quality of Life (QoL) in people with PD. Methods: To achieve the above aim I conducted a systematic review to identify factors associated with medication non-adherence, followed by a Cochrane systematic review on interventions for improving medication adherence in PD. I then tested the efficacy of AT in PD in a randomised controlled trial (RCT). Semistructured interviews were used to explore patients’ experiences of receiving AT. Results: Mood disorders, cognition, poor symptom control/QoL, younger age/longer disease duration, regimen complexity/polypharmacy, risk taking behaviours, poor knowledge of PD/education, lack of spouse/partner, low income, desire to maintain employment and gender were identified as factors associated with non-adherence in PD. Only one study previously investigated an intervention (didactic educational material) for improving medication adherence in PD, according to my Cochrane systematic review. Seventy-six patients and 46 spouse/carers completed the RCT (CAAT-PARK). At week-12 follow-up the active treatment group significantly improved in adherence and QoL compared to the treatment as usual group. Thematic analysis of interviews from 10 patients and 3 spouse/carers suggested that positive effects and attributes of AT may be important for the success of AT. Furthermore, the findings suggested that the mechanism of AT may be bi-directional and associated with improved confidence and self-efficacy. Conclusions: Adherence Therapy improved medication adherence and QoL in PD. A larger pragmatic trial to test the efficacy and cost effectiveness of Adherence Therapy with a control group placebo intervention is required. ISRCTN0783095

Protocol evaluating the effectiveness of a school-based group programme for parents of children at risk of ADHD: The 'PArents, Teachers and CHildren WORKing together (PATCHWORK)' cluster RCT protocol

Introduction Early intervention for childhood behavioural problems may help improve health and educational outcomes in affected children and reduce the likelihood of developing additional difficulties. The National Institute for Health and Clinical Excellence guidelines for attention deficit/hyperactivity disorder (ADHD), a common childhood behavioural disorder, recommend a stepped care approach for the identification and management of these problems. Parents of children with high levels of hyperactivity and inattention may benefit from intervention programmes involving behavioural management and educational approaches. Such interventions may be further enhanced by providing training and feedback to teachers about the strategies discussed with parents. In relation to children with high levels of hyperactivity, impulsiveness and inattention, we aim to test the feasibility and effectiveness of a parenting programme (with and without an accompanying teacher session) in primary schools. Methods and analysis This clustered (at the level of school) randomised controlled trial (RCT) focuses on children in their first four school years (ages 4–8 years) in the East Midlands area of England. Parents will complete a screening measure, the Strengths and Difficulties Questionnaire, to identify children with high levels of hyperactivity/inattention. Three approaches to reducing hyperactivity and attention problems will be compared: a group programme for parents (parent-only intervention); group programme for parents combined with feedback to teachers (combined intervention); and waiting list control (no intervention). Differences between arms on the short version of Conners’ Parent and Teacher Rating Scales Revised will be compared and also used to inform the sample size required for a future definitive cluster RCT. A preliminary cost-effectiveness analysis will also be conducted. Ethics and dissemination The outcomes of this study will inform policy makers about the feasibility, acceptability and effectiveness of delivering targeted behavioural interventions within a school setting. The study has received ethical approval from the University of Nottingham Medical School Ethics Committee

Barriers to colorectal cancer screening among American Indian men aged 50 or older, Kansas and Missouri, 2006-2008

American Indian (AI) men have some of the highest rates of colorectal cancer (CRC) in the United States but among the lowest screening rates. Our goal was to better understand awareness and discourse about colorectal cancer in a heterogeneous group of AI men in the Midwestern United States. Focus groups were conducted with AI men (N = 29); data were analyzed using a community-participatory approach to qualitative text analysis. Several themes were identified regarding knowledge, knowledge sources, and barriers to and facilitators of screening. Men in the study felt that awareness about colorectal cancer was low, and people were interested in learning more. Education strategies need to be culturally relevant and specific

Views, Barriers, and Suggestions for Colorectal Cancer Screening Among American Indian Women Older Than 50 Years in the Midwest

OBJECTIVE: Although colorectal cancer (CRC) mortality rates in the US population have shown a decline, American Indian (AI) CRC mortality rates appear to be increasing. CRC screening rates of AIs remain low when compared with other ethnic groups. The research team explored women's perceptions toward CRC screening, existing barriers, and suggestions to promote education and screening among AI women in Kansas and Missouri. METHODS: Using a community-based participatory research approach, the authors conducted 7 focus groups with AI women older than 50 years (N = 52) to better understand their perceptions of and attitudes toward CRC screening. RESULTS: Women recognized barriers to screening, such as embarrassment, privacy issues, fear, insurance, and cost. They countered perceived barriers through inventive suggestions for education and awareness via social support systems and intergenerational relationships. DISCUSSION: CRC screening interventions for AI must be culturally tailored

Study protocol for a randomized controlled trial comparing the efficacy of a specialist and a generic parenting programme for the treatment of preschool ADHD

BACKGROUND: The New Forest Parenting Programme (NFPP) is a home-delivered, evidence-based parenting programme to target symptoms of attention-deficit/hyperactivity disorder (ADHD) in preschool children. It has been adapted for use with 'hard-to-reach' or 'difficult-to-treat' children. This trial will compare the adapted-NFPP with a generic parenting group-based programme, Incredible Years (IY), which has been recommended for children with preschool-type ADHD symptoms.METHODS/DESIGN: This multicentre randomized controlled trial comprises three arms: adapted-NFPP, IY and treatment as usual (TAU). A sample of 329 parents of preschool-aged children with a research diagnosis of ADHD enriched for hard-to-reach and potentially treatment-resistant children will be allocated to the arms in the ratio 3:3:1. Participants in the adapted-NFPP and IY arms receive an induction visit followed by 12 weekly parenting sessions of 1½ hours (adapted-NFPP) or 2½ hours (IY) over 2.5 years. Adapted-NFPP will be delivered as a one-to-one home-based intervention; IY, as a group-based intervention. TAU participants are offered a parenting programme at the end of the study. The primary objective is to test whether the adapted-NFPP produces beneficial effects in terms of core ADHD symptoms. Secondary objectives include examination of the treatment impact on secondary outcomes, a study of cost-effectiveness and examination of the mediating role of treatment-induced changes in parenting behaviour and neuropsychological function. The primary outcome is change in ADHD symptoms, as measured by the parent-completed version of the SNAP-IV questionnaire, adjusted for pretreatment SNAP-IV score. Secondary outcome measures are: a validated index of behaviour during child's solo play; teacher-reported SNAP-IV (ADHD scale); teacher and parent SNAP-IV (ODD) Scale; Eyberg Child Behaviour Inventory - Oppositional Defiant Disorder scale; Revised Client Service Receipt Inventory - Health Economics Costs measure and EuroQol (EQ5D) health-related quality-of-life measure. Follow-up measures will be collected 6 months after treatment for participants allocated to adapted-NFPP and IY.DISCUSSION: This trial will provide evidence as to whether the adapted-NFPP is more effective and cost-effective than the recommended treatment and TAU. It will also provide information about mediating factors (improved parenting and neuropsychological function) and moderating factors (parent and child genetic factors) in any increased benefit.TRIAL REGISTRATION: Current Controlled Trials, ISRCTN39288126.</p

Reversible Resistance Induced by FLT3 Inhibition: A Novel Resistance Mechanism in Mutant FLT3-Expressing Cells

Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML) are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors.MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression.We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance

The occupation of a box as a toy model for the seismic cycle of a fault

We illustrate how a simple statistical model can describe the quasiperiodic occurrence of large earthquakes. The model idealizes the loading of elastic energy in a seismic fault by the stochastic filling of a box. The emptying of the box after it is full is analogous to the generation of a large earthquake in which the fault relaxes after having been loaded to its failure threshold. The duration of the filling process is analogous to the seismic cycle, the time interval between two successive large earthquakes in a particular fault. The simplicity of the model enables us to derive the statistical distribution of its seismic cycle. We use this distribution to fit the series of earthquakes with magnitude around 6 that occurred at the Parkfield segment of the San Andreas fault in California. Using this fit, we estimate the probability of the next large earthquake at Parkfield and devise a simple forecasting strategy.Comment: Final version of the published paper, with an erratum and an unpublished appendix with some proof

The impact of a computerised test of attention and activity (QbTest) on diagnostic decision-making in children and young people with suspected ADHD: single-blind randomised controlled trial

Background: Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision making in children with suspected ADHD. Methods: Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6-17 years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within six-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). Results: One hundred and thirty two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (Hazard Ratio 1.44, 95% CI 1.04 to 2.01). At six-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (Time Ratio 0.85, 95% CI 0.77 to 0.93), increased clinicians’ confidence in their diagnostic decisions (Odds Ratio 1.77, 95% CI 1.09 to 2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance, however cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as ‘cost neutral’. Conclusion: QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy