The Added Value of Radiographs in Diagnosing Knee Osteoarthritis Is Similar for General Practitioners and Secondary Care Physicians; Data from the CHECK Early Osteoarthritis Cohort

Objective: The purpose of this study was to evaluate the added value of radiographs for diagnosing knee osteoarthritis (KOA) by general practitioners (GPs) and secondary care physicians (SPs). Methods: Seventeen GPs and nineteen SPs were recruited to evaluate 1185 knees from the CHECK cohort (presenters with knee pain in primary care) for the presence of clinically relevant osteoarthritis (OA) during follow-up. Experts were required to make diagnoses independently, first based on clinical data only and then on clinical plus radiographic data, and to provide certainty scores (ranging from 1 to 100, where 1 was “certainly no OA” and 100 was “certainly OA”). Next, experts held consensus meetings to agree on the final diagnosis. With the final diagnosis as gold standard, diagnostic indicators were calculated (sensitivity, specificity, positive/negative predictive value, accuracy and positive/negative likelihood ratio) for all knees, as well as for clinically “certain” and “uncertain” knees, respectively. Student paired t-tests compared certainty scores. Results: Most diagnoses of GPs (86%) and SPs (82%) were “consistent” after assessment of radiographic data. Diagnostic indicators improved similarly for GPs and SPs after evaluating the radiographic data, but only improved relevantly in clinically “uncertain” knees. Radiographs added some certainty to “consistent” OA knees (GP 69 vs. 72, p < 0.001; SP 70 vs. 77, p < 0.001), but not to the consistent no OA knees (GP 21 vs. 22, p = 0.16; SP 20 vs. 21, p = 0.04). Conclusions: The added value of radiographs is similar for GP and SP, in terms of diagnostic accuracy and certainty. Radiographs appear to be redundant when clinicians are certain of their clinical diagnosi

Age Does Matter in Adolescents and Young Adults versus Older Adults with Advanced Melanoma; A National Cohort Study Comparing Tumor Characteristics, Treatment Pattern, Toxicity and Response

Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults (AYAs, 15-39 years of age). However, AYAs are underrepresented in clinical trials investigating new therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively collected nation-wide data from the Dutch Melanoma Treatment Registry (DMTR), we compared baseline characteristics, mutational profiles, treatment strategies, grade 3-4 adverse events (AEs), responses and outcomes in AYAs (n = 210) and older adults (n = 3775) who were diagnosed with advanced melanoma between July 2013 and July 2018. Compared to older adults, AYAs were more frequently female (51% versus 40%, p = 0.001), and had a better Eastern Cooperative Oncology Group performance status (ECOG 0 in 54% versus 45%, p = 0.004). BRAF and NRAS mutations were age dependent, with more BRAF V600 mutations in AYAs (68% versus 46%) and more NRAS mutations in older adults (13% versus 21%), p < 0.001. This finding translated in distinct first-line treatment patterns, where AYAs received more initial targeted therapy. Overall, grade 3-4 AE percentages following first-line systemic treatment were similar for AYAs and older adults; anti-PD-1 (7% versus 14%, p = 0.25), anti-CTLA-4 (16% versus 33%, p = 0.12), anti-PD-1 + anti-CTLA-4 (67% versus 56%, p = 0.34) and BRAF/MEK-inhibition (14% versus 23%, p = 0.06). Following anti-CTLA-4 treatment, no AYAs experienced a grade 3-4 colitis, while 17% of the older adults did (p = 0.046). There was no difference in response to treatment between AYAs and older adults. The longer overall survival observed in AYAs (hazard ratio (HR) 0.7; 95% CI 0.6-0.8) was explained by the increased cumulative incidence of non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5-4.9), calculated by competing risk analysis. The results of our national cohort study show that baseline characteristics and mutational profiles differ between AYAs and older adults with advanced melanoma, leading to different treatment choices made in daily practice. Once treatment is initiated, AYAs and older adults show similar tumor responses and melanoma-specific survival

The PLANES study: a protocol for a randomised controlled feasibility study of the placental growth factor (PlGF) blood test-informed care versus standard care alone for women with a small for gestational age fetus at or after 32 + 0 weeks' gestation.

BackgroundStillbirth remains a major concern across the globe and in some high-resource countries, such as the UK; efforts to reduce the rate have achieved only modest reductions. One third of stillborn babies are small for gestational age (SGA), and these pregnancies are also at risk of neonatal adverse outcomes and lifelong health problems, especially when delivered preterm. Current UK clinical guidance advocates regular monitoring and early term delivery of the SGA fetus; however, the most appropriate regimen for surveillance of these babies remains unclear and often leads to increased intervention for a large number of these women. This pilot trial will determine the feasibility of a large-scale trial refining the risk of adverse pregnancy outcome in SGA pregnancies using biomarkers of placental function sFlt-1/PlGF, identifying and intervening in only those deemed at highest risk of stillbirth.MethodsPLANES is a randomised controlled feasibility study of women with an SGA fetus that will be conducted at two tertiary care hospitals in the UK. Once identified on ultrasound, women will be randomised into two groups in a 3:1 ratio in favour of sFlt-1/PlGF ratio led management vs standard care. Women with an SGA fetus and a normal sFlt-1/PlGF ratio will have a repeat ultrasound and sFlt-1/PlGF ratio every 2 weeks with planned birth delayed until 40 weeks. In those women with an SGA fetus and an abnormal sFlt-1/PlGF ratio, we will offer birth from 37 weeks or sooner if there are other concerning features on ultrasound. Women assigned to standard care will have an sFlt-1/PlGF ratio taken, but the results will be concealed from the clinical team, and the woman's pregnancy will be managed as per the local NHS hospital policy. This integrated mixed method study will also involve a health economic analysis and a perspective work package exploring trial feasibility through interviews and questionnaires with participants, their partners, and clinicians.DiscussionOur aim is to determine feasibility through the assessment of our ability to recruit and retain participants to the study. Results from this pilot study will inform the design of a future large randomised controlled trial that will be adequately powered for adverse pregnancy outcome. Such a study would provide the evidence needed to guide future management of the SGA fetus.Trial registrationISRCTN58254381 . Registered on 4 July 2019