Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership

Objectives: The Acne Priority Setting Partnership (PSP) was set up to identify and rank treatment uncertainties by bringing together people with acne, and professionals providing care within and beyond the National Health Service (NHS). Setting: The UK with international participation. Participants: Teenagers and adults with acne, parents, partners, nurses, clinicians, pharmacists, private practitioners. Methods: Treatment uncertainties were collected via separate online harvesting surveys, embedded within the PSP website, for patients and professionals. A wide variety of approaches were used to promote the surveys to stakeholder groups with a particular emphasis on teenagers and young adults. Survey submissions were collated using keywords and verified as uncertainties by appraising existing evidence. The 30 most popular themes were ranked via weighted scores from an online vote. At a priority setting workshop, patients and professionals discussed the 18 highest-scoring questions from the vote, and reached consensus on the top 10. Results: In the harvesting survey, 2310 people, including 652 professionals and 1456 patients (58% aged 24 y or younger), made submissions containing at least one research question. After checking for relevance and rephrasing, a total of 6255 questions were collated into themes. Valid votes ranking the 30 most common themes were obtained from 2807 participants. The top 10 uncertainties prioritised at the workshop were largely focused on management strategies, optimum use of common prescription medications and the role of nondrug based interventions. More female than male patients took part in the harvesting surveys and vote. A wider range of uncertainties were provided by patients compared to professionals. Conclusions: Engaging teenagers and young adults in priority setting is achievable using a variety of promotional methods. The top 10 uncertainties reveal an extensive knowledge gap about widely used interventions and the relative merits of drug versus non-drug based treatments in acne management

Prognostic Impact of KRAS Mutation Subtypes in 677 Patients with Metastatic Lung Adenocarcinomas

BackgroundWe previously demonstrated that patients with metastatic KRAS mutant lung cancers have a shorter survival compared with patients with KRAS wild-type cancers. Recent reports have suggested different clinical outcomes and distinct activated signaling pathways depending on KRAS mutation subtype. To better understand the impact of KRAS mutation subtype, we analyzed data from 677 patients with KRAS mutant metastatic lung cancer.MethodsWe reviewed all patients with metastatic or recurrent lung cancers found to have KRAS mutations over a 6-year time period. We evaluated the associations among KRAS mutation type, clinical factors, and overall survival in univariate and multivariate analyses. Any significant findings were validated in an external multi-institution patient dataset.ResultsAmong 677 patients with KRAS mutant lung cancers (53 at codon 13, 624 at codon 12), there was no difference in overall survival for patients when comparing KRAS transition versus transversion mutations (p = 0.99), smoking status (p = 0.33), or when comparing specific amino acid substitutions (p = 0.20). In our dataset, patients with KRAS codon 13 mutant tumors (n = 53) had shorter overall survival compared with patients with codon 12 mutant tumors (n = 624) (1.1 versus 1.3 years, respectively; p = 0.009), and the findings were confirmed in a multivariate Cox model controlling for age, sex, and smoking status (hazard ratio: 1.52, 95% confidence interval: 1.11–2.08; p = 0.008). In an independent validation set of tumors from 682 patients with stage IV KRAS mutant lung cancers, there was no difference in survival between patients with KRAS codon 13 versus codon 12 mutations (1.0 versus 1.1 years, respectively; p = 0.41).ConclusionsAmong individuals with KRAS mutant metastatic lung cancers treated with conventional therapy, there are no apparent differences in outcome based on KRAS mutation subtype

A new anisotropy index on trabecular bone radiographic images using the fast Fourier transform

BACKGROUND: The degree of anisotropy (DA) on radiographs is related to bone structure, we present a new index to assess DA. METHODS: In a region of interest from calcaneus radiographs, we applied a Fast Fourier Transform (FFT). All the FFT spectra involve the horizontal and vertical components corresponding respectively to longitudinal and transversal trabeculae. By visual inspection, we measured the spreading angles: Dispersion Longitudinal Index (DLI) and Dispersion Transverse Index (DTI) and calculated DA = 180/(DLI+DTI). To test the reliability of DA assessment, we synthesized images simulating radiological projections of periodic structures with elements more or less disoriented. RESULTS: Firstly, we tested synthetic images which comprised a large variety of structures from highly anisotropic structure to the almost isotropic, DA was ranging from 1.3 to 3.8 respectively. The analysis of the FFT spectra was performed by two observers, the Coefficients of Variation were 1.5% and 3.1 % for intra-and inter-observer reproducibility, respectively. In 22 post-menopausal women with osteoporotic fracture cases and 44 age-matched controls, DA values were respectively 1.87 ± 0.15 versus 1.72 ± 0.18 (p = 0.001). From the ROC analysis, the Area Under Curve (AUC) were respectively 0.65, 0.62, 0.64, 0.77 for lumbar spine, femoral neck, total femoral BMD and DA. CONCLUSION: The highest DA values in fracture cases suggest that the structure is more anisotropic in osteoporosis due to preferential deletion of trabeculae in some directions

Data from: Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership

Objectives: The Acne Priority Setting Partnership (PSP) was set up to identify and rank treatment uncertainties by bringing together people with acne and professionals providing care within and beyond the NHS. Setting: The UK with international participation. Participants: Teenagers and adults with acne, parents, partners, nurses, clinicians, pharmacists, private practitioners. Methods: Treatment uncertainties were collected via separate online harvesting surveys, embedded within the PSP website, for patients and professionals. A wide variety of approaches were used to promote the surveys to stakeholder groups with a particular emphasis on teenagers and young adults. Survey submissions were collated using keywords and verified as uncertainties by appraising existing evidence. The 30 most popular themes were ranked via weighted scores from an online vote. At a priority setting workshop, patients and professionals discussed the 18 highest-scoring questions from the vote and reached consensus on the top ten. Results: In the harvesting survey, 2,310 people including 652 professionals and 1,456 patients (58% aged 24 y or younger) made submissions containing at least one research question. After checking for relevance and rephrasing, a total of 6,255 questions were collated into themes. Valid votes ranking the 30 most common themes were obtained from 2,807 participants. The top ten uncertainties prioritised at the workshop were largely focused on management strategies, optimum use of common prescription medications and the role of non-drug based interventions. More female than male patients took part in the harvesting surveys and vote. A wider range of uncertainties were provided by patients compared to professionals. Conclusions: Engaging teenagers and young adults in priority setting is achievable using a variety of promotional methods. The top ten uncertainties reveal an extensive knowledge gap about widely used interventions and the relative merits of drug versus non-drug based treatments in acne management

Acne PSP harvesting survey professional version no identifiers 220315

The raw unedited submissions to the Acne PSP harvesting survey for the collection of treatment uncertainties are contained in the following Excel files: Acne PSP harvesting survey patient version no identifiers 230315 Acne PSP harvesting survey professional version no identifiers 230315 All potential personal identifiers have been removed (age range, gender, ethnicity, first part of postcode) but could be made available on request for anyone who wishes to use them in their analyses and has the necessary ethical and, if required, NHS governance approvals. For each data set, null entries (i.e. those submissions which did not contain any entries in the columns to collect treatment uncertainties) have been removed. The submissions are listed in the order they were received. In the patient version, treatment uncertainties could be entered into any of columns D through to K. In the professional version, treatment uncertainties could be entered into any of columns B, D, F, H and J. At the close of the survey, submitted text was rephrased as required in order to separate out individual questions. Many submissions were not written as questions; where one or more questions could reasonably be inferred from the submitted text, they were extracted and included in totals. The total number of questions in the journal article refers to the number of questions in scope after rephrasing. An unlimited number of keywords (MesH descriptors wherever possible) were added to each separate question to enable collation by theme and/or by intervention type. Further information can be obtained from: Dr E Anne Eady, [email protected] Tel: 01943 608823 OR Dr Alison Layton, [email protected] Tel: 01423 553364 Fax: 01423 55340

Acne PSP harvesting survey patient version no identifiers 230315

Acne PSP harvesting survey patient version no identifiers 23031

Monitoring therapeutic response and resistance: analysis of circulating tumor DNA in patients with ALK+ lung cancer.

INTRODUCTION: Despite initial effectiveness of ALK tyrosine kinase inhibitors (TKIs) in patients with ALK+ non-small cell lung cancer (NSCLC), therapeutic resistance will ultimately develop. Serial tracking of genetic alterations detected in circulating tumor DNA (ctDNA) can be an informative strategy to identify response and resistance. This study evaluated the utility of analyzing ctDNA as a function of response to ensartinib, a potent second-generation ALK TKI. METHODS: Pre-treatment plasma was collected from 76 patients with ALK+ NSCLC who were ALK TKI naïve or had received prior ALK TKI, and analyzed for specific genetic alterations. Longitudinal plasma samples were analyzed from a subset (N=11) of patients. Analysis of pre-treatment tumor biopsies from 22 patients was compared with plasma. RESULTS: Disease-associated genetic alterations were detected in 74% (56/76) of patients, the most common being EML4-ALK. Concordance of ALK fusion between plasma and tissue was 91% (20/22). Twenty-four ALK kinase domain mutations were detected in 15 patients, all had previously received an ALK TKI; G1269A was the most prevalent (4/24). Patients with a detectable EML4-ALK variant 1 (V1) fusion had improved response (9/17, 53%) to ensartinib compared to patients with EML4-ALK V3 fusion (1/7, 14%). Serial changes in ALK alterations were observed during therapy. CONCLUSIONS: Clinical utility of ctDNA was demonstrated, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients that may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs