BACKGROUND Human papilloma virus(HPV)-associated oropharyngeal cancer(OPC) treated with chemoradiation has an excellent prognosis leading to the question of whether de-escalated radiotherapy can result in a similar outcome. Hypoxia is a known negative prognostic factor for OPC. A prospective multi-arm IRB #)-070 study using functional imaging to assess pre/intra-treatment hypoxia for all head and neck cancer is currently on-going. A subset study of this large multi-arm study was designed to test functional imaging response as a selection criteria for de-escalation to gross nodal disease in HPV-associated OPC patients receiving concurrent chemoradiation. METHODS Patients with HPV-positive oropharyngeal carcinoma were enrolled on an IRB approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment 18F-FDG (Fluorodeoxyglucose) and dynamic 18F-FMISO(fluoromisonidazole) positron emission PET were performed. For patients with pretreatment hypoxia on18F-FMISO PET(defined >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done one week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10 Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis(DM)-free, and overall survival(OS) rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image-guidance. RESULTS 33 HPV+ OPC patients were enrolled in this pilot study. 100% showed pre-treatment hypoxia[at primary site and/or node(s)] and among these, 48% resolved[at primary site and/or node(s)] 30% met criteria and received 10Gy reduction to the lymph node(s). At the median follow-up of 32 months[21–61 months], the 2-year locoregional control was 100%. One patient failed distantly with persistence of hypoxia on 18F-FMISO PET. The 2-year DM-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically. CONCLUSIONS Hypoxia is present in HPV+ tumors, but resolves within 1 week of treatment in 48% of cases either at the primary site and/or Lymph node(s). Our 100% locoregional control suggests that intra-treatment functional imaging used to selectively de-escalate node(s) to 60Gy was confirmed safe using our stringent imaging criteria. Intra-treatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

BackgroundDiagnostic accuracy might be improved by algorithms that searched patients’ clinical notes in the electronic health record (EHR) for signs and symptoms of diseases such as multiple sclerosis (MS). The focus this study was to determine if patients with MS could be identified from their clinical notes prior to the initial recognition by their healthcare providers.MethodsAn MS-enriched cohort of patients with well-established MS (n = 165) and controls (n = 545), was generated from the adult outpatient clinic. A random sample cohort was generated from randomly selected patients (n = 2289) from the same adult outpatient clinic, some of whom had MS (n = 16). Patients’ notes were extracted from the data warehouse and signs and symptoms mapped to UMLS terms using MedLEE. Approximately 1000 MS-related terms occurred significantly more frequently in MS patients’ notes than controls’. Synonymous terms were manually clustered into 50 buckets and used as classification features. Patients were classified as MS or not using Naïve Bayes classification.ResultsClassification of patients known to have MS using notes of the MS-enriched cohort entered after the initial ICD9[MS] code yielded an ROC AUC, sensitivity, and specificity of 0.90 [0.87-0.93], 0.75[0.66-0.82], and 0.91 [0.87-0.93], respectively. Similar classification accuracy was achieved using the notes from the random sample cohort. Classification of patients not yet known to have MS using notes of the MS-enriched cohort entered before the initial ICD9[MS] documentation identified 40% [23–59%] as having MS. Manual review of the EHR of 45 patients of the random sample cohort classified as having MS but lacking an ICD9[MS] code identified four who might have unrecognized MS.ConclusionsDiagnostic accuracy might be improved by mining patients’ clinical notes for signs and symptoms of specific diseases using NLP. Using this approach, we identified patients with MS early in the course of their disease which could potentially shorten the time to diagnosis. This approach could also be applied to other diseases often missed by primary care providers such as cancer. Whether implementing computerized diagnostic support ultimately shortens the time from earliest symptoms to formal recognition of the disease remains to be seen.

Aims Although systemic embolism is a potential complication in transthyretin amyloid cardiomyopathy (ATTR‐CM), data about its incidence and prevalence are scarce. We studied the incidence, prevalence and factors associated with embolic events in ATTR‐CM. Additionally, we evaluated embolic events according to the type of oral anticoagulation (OAC) and the performance of the CHA2DS2‐VASc score in this setting. Methods and results Clinical characteristics, history of atrial fibrillation (AF) and embolic events were retrospectively collected from ATTR‐CM patients evaluated at four international amyloid centres. Overall, 1191 ATTR‐CM patients (87% men, median age 77.1 years [interquartile range‐IQR 71.4–82], 83% ATTRwt) were studied. A total of 162 (13.6%) have had an embolic event before initial evaluation. Over a median follow‐up of 19.9 months (IQR 9.9–35.5), 41 additional patients (3.44%) had an embolic event. Incidence rate (per 100 patient‐years) was 0 among patients in sinus rhythm with OAC, 1.3 in sinus rhythm without OAC, 1.7 in AF with OAC, and 4.8 in AF without OAC. CHA2DS2‐VASc did not predict embolic events in patients in sinus rhythm whereas in patients with AF without OAC, only those with a score ≥4 had embolic events. There was no difference in the incidence rate of embolism between patients with AF treated with vitamin K antagonists (VKAs) (n = 322) and those treated with direct oral anticoagulants (DOACs) (n = 239) (p = 0.66). Conclusions Embolic events were a frequent complication in ATTR‐CM. OAC reduced the risk of systemic embolism. Embolic rates did not differ with VKAs and DOACs. The CHA2DS2‐VASc score did not correlate well with clinical outcome in ATTR‐CM and should not be used to assess thromboembolic risk in this population.

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OBJECTIVE: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care.SETTING: Thirteen districts across three South African provinces.DESIGN: This descriptive study examined laboratory and healthcare facility records of 194 patients diagnosed with RR-TB in the third quarter of 2016.RESULTS: The median age was 35 years; 120/194 (62%) of patients were male. Previous TB treatment was documented in 122/194 (63%) patients and 56/194 (29%) had a record of fluoroquinolone and/or second-line injectable resistance. Of 134 (69%) HIV-positive patients, viral loads were available for 68/134 (51%) (36/68 [53%] had viral loads of >1000 copies/ml) and CD4 counts were available for 92/134 (69%) (20/92 [22%] had CD4 <50 cells/mm3). Patients presented with varying other comorbidities, including hypertension (13/194, 7%) and mental health conditions (11/194, 6%). Of 194 patients, 44 (23%) were reported to be employed. Other socio-economic challenges included substance abuse (17/194, 9%) and ill family members (17/194, 9%). Respectively 13% and 42% of patients were estimated to travel more than 20 km to reach their diagnosing and treatment-initiating healthcare facility.CONCLUSIONS: RR-TB patients had diverse medical and social challenges highlighting the need for integrated, differentiated and patient-centred healthcare to better address specific needs and underlying vulnerabilities of individual patients.