Progress and pitfalls with the use of image-guided personalised approaches in lymphoma

The use of 18F-FDG PET CT has become an essential part of the management of patients with lymphoma. The last decade has seen unrivalled progress in research efforts to personalise treatment approaches using PET as a predictive imaging biomarker. Critical to this success has been the standardisation of PET methods and reporting, including the 5-point Deauville scale, which has enabled the delivery of robust clinical trial data to develop response-adapted treatment approaches.(1, 2) The utility of PET as a predictive imaging biomarker in assessing treatment success or failure has been investigated extensively in malignant lymphomas. Considerable progress has been made over the last decade, in using PET to direct more personalised “risk-adapted” approaches, as well as an increased understanding of some of the limitations. Arguably the greatest success has been in Hodgkin Lymphoma (HL) where PET was initially demonstrated to be a powerful predictive biomarker (3) and is now routinely used in both early-stage and advanced HL to reduce or escalate the use of chemotherapy as well as guiding the delivery of more selective radiotherapy to patients.

The CloudUPDRS smartphone software in Parkinson’s study: cross-validation against blinded human raters

Digital assessments of motor severity could improve the sensitivity of clinical trials and personalise treatment in Parkinson’s disease (PD) but have yet to be widely adopted. Their ability to capture individual change across the heterogeneous motor presentations typical of PD remains inadequately tested against current clinical reference standards. We conducted a prospective, dual-site, crossover-randomised study to determine the ability of a 16-item smartphone-based assessment (the index test) to predict subitems from the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) as assessed by three blinded clinical raters (the reference-standard). We analysed data from 60 subjects (990 smartphone tests, 2628 blinded video MDS-UPDRS III subitem ratings). Subject-level predictive performance was quantified as the leave-one-subject-out cross-validation (LOSO-CV) accuracy. A pre-specified analysis classified 70.3% (SEM 5.9%) of subjects into a similar category to any of three blinded clinical raters and was better than random (36.7%; SEM 4.3%) classification. Post hoc optimisation of classifier and feature selection improved performance further (78.7%, SEM 5.1%), although individual subtests were variable (range 53.2–97.0%). Smartphone-based measures of motor severity have predictive value at the subject level. Future studies should similarly mitigate against subjective and feature selection biases and assess performance across a range of motor features as part of a broader strategy to avoid overly optimistic performance estimates.

Will we ever cure nasal polyps?

BACKGROUND Nasal polyposis is a benign hyperplastic growth of nasal mucosa. There is a paucity of evidence on the prevalence and incidence of nasal polyposis. Although nasal polyps can be asymptomatic, they can cause a spectrum of nasal problems including nasal obstruction, rhinorrhoea, nasal congestion, anosmia resulting in ageusia. Nasal polyps are mostly associated with chronic rhinosinusitis, The current management of chronic rhinosinusitis with nasal polyps is controversial and is not curative. METHODS A Medline search was conducted, using the keywords ‘rhinosinusitis’, ‘sinusitis’, ‘classification’ and ‘’aetiology. FINDINGS The current treatment of nasal polyposis in chronic rhinosinusitis with nasal polyps is still challenging. Emerging research through endotypes profiling aims to better understand the complexities of this heterogeneous disease to personalise treatment and provide a cure. Randomised controlled trials aim to provide robust evidence for current management options.

Inhaled antibiotics: dry or wet?

Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment ofPseudomonas aeruginosain cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser. The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching.In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics. The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed.

Focusing on drug versus disease mechanisms and on clinical subgrouping to advance personalised medicine in psychiatry

Personalised medicine has finally been featured in psychiatric journals, but psychiatrists have mainly focused on the promise of using disease mechanisms to personalise treatment. Psychiatric disorders such as schizophrenia and depression are not diseases, in the medical sense, and are probably more like syndromes. Instead of spending much time and effort focusing on the mechanisms of diseases that may instead be syndromes, the author believes that psychiatrists should (1) learn more about personalising prescription via drug mechanisms, a pharmacological approach to personalised medicine; and (2) reconsider prior attempts by traditional clinical psychopharmacologists to use sophisticated clinical approaches that try to subdivide psychiatric syndromes into groups that may be more homogenous for treatment response.

Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial

BackgroundAntidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).AimsTo test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants.MethodIn an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163).ResultsAltogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score at 6 weeks was 0.50 (95% CI −2.04 to 3.03, P = 0.70), which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype.ConclusionsIt is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.