Services for young people with attention deficit/hyperactivity disorder transitioning from child to adult mental health services: a national survey of mental health trusts in England.

Transition from child to adult mental health services is considered to be a difficult process, particularly for individuals with neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD). This article presents results from a national survey of 36 mental health National Health Service (NHS) trusts across England, the findings indicate a lack of accurate data on the number of young people with ADHD transitioning to, and being seen by, adult services. Less than half of the trusts had a specialist adult ADHD service and in only a third of the trusts were there specific commissioning arrangements for adult ADHD. Half of the trusts reported that young people with ADHD were prematurely discharged from child and adolescent mental health services (CAMHS) because there were no suitable adult services. There was also a lack of written transition protocols, care pathways, commissioned services for adults with ADHD and inadequate information sharing between services. The findings advocate the need to provide a better transition service underpinned by clear, structured guidelines and protocols, routine data collection and information sharing across child and adult services. An increase in the commission of specialist adult ADHD clinics is needed to ensure individuals have access to appropriate support and care

The challenges of implementing ADHD clinical guidelines and research best evidence in routine clinical care settings: a Delphi survey and mixed-methods study

Background The landmark US Multimodal Treatment of ADHD (MTA) study established the benefits of individualised medication titration and optimisation strategies to improve short- to medium-term outcomes in attention-deficit hyperactivity disorder (ADHD). This individualised medication management approach was subsequently incorporated into the National Institute for Health and Care Excellence (NICE) ADHD Clinical Guidelines (NICE CG78). However, little is known about clinicians’ attitudes towards implementing these medication management strategies for ADHD in routine care. Aims To examine National Health Service (NHS) healthcare professionals’ consensus on ADHD medication management strategies. Method Using the Delphi method, we examined perceptions on the importance and feasibility of implementing 103 ADHD treatment statements from sources including the UK NICE ADHD guidelines and US medication management algorithms. Results Certain recommendations for ADHD medication management were judged as important and feasible to implement, including a stepwise titration of stimulant medication. Other recommendations were perceived as important but not feasible to implement in routine practice, such as weekly clinic follow-up with the family during titration and collection of follow-up symptom questionnaires. Conclusions Many of the key guideline recommendations for ADHD medication management are viewed by clinicians as important and feasible to implement. However, some recommendations present significant implementation challenges within the context of routine NHS clinical care in England

Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study.

OBJECTIVE: Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome "resistance" in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. METHODS: Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. RESULTS: Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. CONCLUSIONS: Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment

Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier.

BACKGROUND: TP53 and BRCA1/2 mutations are the main drivers in high-grade serous ovarian carcinoma (HGSOC). We hypothesise that combining tissue phenotypes from image analysis of tumour sections with genomic profiles could reveal other significant driver events. RESULTS: Automatic estimates of stromal content combined with genomic analysis of TCGA HGSOC tumours show that stroma strongly biases estimates of PTEN expression. Tumour-specific PTEN expression was tested in two independent cohorts using tissue microarrays containing 521 cases of HGSOC. PTEN loss or downregulation occurred in 77% of the first cohort by immunofluorescence and 52% of the validation group by immunohistochemistry, and is associated with worse survival in a multivariate Cox-regression model adjusted for study site, age, stage and grade. Reanalysis of TCGA data shows that hemizygous loss of PTEN is common (36%) and expression of PTEN and expression of androgen receptor are positively associated. Low androgen receptor expression was associated with reduced survival in data from TCGA and immunohistochemical analysis of the first cohort. CONCLUSION: PTEN loss is a common event in HGSOC and defines a subgroup with significantly worse prognosis, suggesting the rational use of drugs to target PI3K and androgen receptor pathways for HGSOC. This work shows that integrative approaches combining tissue phenotypes from images with genomic analysis can resolve confounding effects of tissue heterogeneity and should be used to identify new drivers in other cancers.This work was supported by Cancer Research UK [grant numbers A15601, A17197,A16561, A10124]; the University of Cambridge; National Institute for Health Research Cambridge Biomedical Research Centre and Academic Clinical Fellowship scheme (FCM); Cambridge Experimental Cancer Medicine Centre and Hutchison Whampoa Limited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://genomebiology.com/2014/15/12/526

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

‘Mind the gap’ - mapping services for young people with ADHD transitioning from child to adult mental health services

Background: Once considered to be a disorder restricted to childhood, Attention Deficit/Hyperactivity Disorder (ADHD) is now recognised to persist into adult life. However, service provision for adults with ADHD is limited. Additionally, there is little guidance or research on how best to transition young people with ADHD from child to adult services. Method: We report the findings of a survey of 96 healthcare professionals working in children’s (Child and Adolescent Mental Health Services and Community Paediatrics) and adult services across five NHS Trusts within the East Midlands region of England to gain a better understanding of the current provision of services for young people with ADHD transitioning into adult mental health services. Results: Our findings indicate a lack of structured guidelines on transitioning and little communication between child and adult services. Child and adult services had differing opinions on what they felt adult services should provide for ADHD cases. Adult services reported feeling ill-prepared to deal with ADHD patients, with clinicians in these services citing a lack of specific knowledge of ADHD and a paucity of resources to deal with such cases. Conclusions: We discuss suggestions for further research, including the need to map the national provision of services for adults with ADHD, and provide recommendations for commissioned adult ADHD services. We specifically advocate an increase in ADHD-specific training for clinicians in adult services, the development of specialist adult ADHD clinics and greater involvement of Primary Care to support the work of generic adult mental health services in adult ADHD management

We need timely access to mental health data: implications of the Goldacre review

The Goldacre review, published in April, 2022, 1 is a landmark evaluation of the use, availability, and safety of National Health Service (NHS) data across all four nations of the UK. The review underscores the necessary role of data in driving health-care improvement and innovation, and the potential risks inherent in using data routinely contributed by health service users. The review recommends a radical overhaul in NHS data curation, access, and analysis, and, crucially, argues that substantial new resources must be marshalled to make this aspiration a reality

A qualitative process evaluation of electronic session-by-session outcome measurement in child and adolescent mental health services

Background: Regular monitoring of patient progress is important to assess the clinical effectiveness of an intervention. Recently, initiatives within UK child and adolescent mental health services (CAMHS) have advocated the use of session-by-session monitoring to continually evaluate the patient’s outcome throughout the course of the intervention. However, the feasibility and acceptability of such regular monitoring is unknown. Method: Semi-structured qualitative interviews were conducted with clinicians (n= 10), administrative staff (n=8) and families (n= 15) who participated in a feasibility study of an electronic session-by-session outcome monitoring tool, (SxS), which is based on the Strengths and Difficulties Questionnaire (SDQ). This study took place in three CAMHS clinics in Nottinghamshire. The interview transcripts were thematically analysed. Results: We found clinicians accepted the need to complete outcome measures, particularly valuing those completed by the patient. However, there were some difficulties with engaging clinicians in this practice and in the training offered. Generally, patients were supportive of completing SxS in the waiting room prior to the clinic session and assistance with the process from administrative staff was seen to be a key factor

Exploratory Analysis of <i>TP53</i> Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

<div><p>Background</p><p>Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic <i>TP53</i> mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP).</p><p>Methods and Findings</p><p>We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific <i>TP53</i> assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The <i>TP53</i> mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP.</p><p>The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%–22%) compared to 0.7% (IQR 0.3%–2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson <i>r =</i> 0.59, <i>p <</i> 0.001), and this correlation improved when patients with ascites were excluded (<i>r =</i> 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm³) than in untreated patients (0.0008% per cm³, <i>p =</i> 0.004). In nearly all relapsed patients with disease volume > 32 cm³, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28–54) compared with a median time to nadir of 84 d (IQR 42–116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07–0.67, <i>p =</i> 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%–92%) and 88% specificity (95% CI 64%–99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort.</p><p>Conclusions</p><p>In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.</p></div