Development of a rapid and quantitative lateral flow assay for the simultaneous measurement of serum κ and λ immunoglobulin free light chains (FLC): inception of a new near-patient FLC screening tool.

BACKGROUND: Serum free light chains (FLC) are sensitive biomarkers used for the diagnosis and management of plasma cell dyscrasias, such as multiple myeloma (MM), and are central to clinical screening algorithms and therapy response criteria. We have developed a portable, near-patient, lateral-flow test (Seralite®) that quantitates serum FLC in 10 min, and is designed to eliminate sample processing delays and accelerate decision-making in the clinic. METHODS: Assay interference, imprecision, lot-to-lot variability, linearity, and the utility of a competitive-inhibition design for the elimination of antigen-excess ('hook effect') were assessed. Reference ranges were calculated from 91 healthy donor sera. Preliminary clinical validation was conducted by retrospective analysis of sera from 329 patients. Quantitative and diagnostic results were compared to Freelite®. RESULTS: Seralite® gave a broad competitive-inhibition calibration curve from below 2.5 mg/L to above 200 mg/L, provided good assay linearity (between 1.6 and 208.7 mg/L for κ FLC and between 3.5 and 249.7 mg/L for λ FLC) and sensitivity (1.4 mg/L for κ FLC and 1.7 mg/L for λ FLC), and eliminated anomalous results from antigen-excess. Seralite® gave good diagnostic concordance with Freelite® (Roche Hitachi Cobas C501) identifying an abnormal FLC ratio and FLC difference in 209 patients with newly diagnosed MM and differentiating these patients from normal healthy donors with polyclonal FLC. CONCLUSIONS: Seralite® sensitively quantitates FLC and rapidly identifies clinical conditions where FLC are abnormal, including MM.

Multiple myeloma can be accurately diagnosed in acute kidney injury patients using a rapid serum free light chain test.

BACKGROUND: Acute kidney injury (AKI) is common in patients with multiple myeloma (MM). Whether serum free light chain (sFLC) measurements can distinguish between myeloma and other causes of AKI requires confirmation to guide early treatment. A rapid and portable sFLC test (Seralite®) is newly available and could reduce delays in obtaining sFLC results and accelerate diagnosis in patients with unexplained AKI. This study evaluated the accuracy of Seralite® to identify MM as the cause of AKI. METHOD: sFLCs were retrospectively analysed in patients with AKI stage 3 as per KDIGO criteria (i.e. serum creatinine ≥354 µmol/L or those on dialysis treatment) (n = 99); 45/99 patients had a confirmed MM diagnosis. RESULTS: The Seralite® κ:λ FLC ratio accurately diagnosed all MM patients in the presence of AKI: a range of 0.14-2.02 returned 100% sensitivity and specificity for identifying all non-myeloma related AKI patients. The sFLC difference (dFLC) also demonstrated high sensitivity (91%) and specificity (100%): an optimal cut-off of 399 mg/L distinguished between myeloma and non-myeloma AKI patients. We propose a pathway of patient screening and stratification in unexplained AKI for use of Seralite® in clinical practice, with a κ:λ ratio range of 0.14-2.02 and dFLC 400 mg/L as decision points. CONCLUSIONS: Seralite® accurately differentiates between AKI due to MM and AKI due to other causes in patients considered at risk of myeloma. This rapid test can sensitively screen for MM in patients with AKI and help inform early treatment intervention.

Does the structure of the medical consultation align with an educational model of clinical communication? A study of physicians' consultations from a postgraduate examination.

OBJECTIVE: This study examined whether the structure of consultations in which physicians were tasked with sharing information corresponded to the chronological stages proposed by an established educational model of clinical communication. METHOD: Seventy six simulated consultations from a postgraduate examination for general medical hospital physicians were transcribed verbatim and converted into diagrams showing consultation structure. All doctor-patient/relative talk was allocated into six phases: Initiating, Gathering information, Summary, Explanation, Planning and Closing, using the 'communication process skills' from the Calgary-Cambridge Guide to the Medical Interview. RESULTS: The majority of consultations included four or five of the expected phases, with most talk (41-92%) in Explanation and Planning. There was no discernible consistency of structure across the consultations or in consultations from the same scenario. Consultations varied in the presence, sequential order, size, location and reappearance of phases. CONCLUSIONS: The structure of consultations in this standardised setting bore little resemblance to the chronological order of phases predicted by an educational model. PRACTICE IMPLICATIONS: Educational guidance and interventions to support patients in preparing for consultations need to take account of doctors' behaviour in practice. Assumptions about the organisation of medical consultations should be queried in the absence of an evidence base.

What does the structure of a medical consultation look like? A new method for visualising doctor-patient communication.

OBJECTIVE: This project developed an innovative methodology for visualising consultation structure by categorising doctor-patient talk into the phases proposed by an established educational model of clinical communication. METHOD: Consultation phases were identified from verbatim transcripts using the tasks and process skills of the Calgary-Cambridge Guide to the Medical Interview. Seventy-eight simulated consultations from a 'History-taking' station of a postgraduate examination for physicians were analysed by two independent raters. Transcripts were converted into diagrams comprising up to six phases: Initiating, Gathering information, Summary, Explanation, Planning and Closing. RESULTS: The dominant phases were Gathering information, Planning and Explanation (66 %, 10 % and 12 % of talk respectively). While consultations broadly followed the expected chronological sequence, less than a third (23/78) contained all six phases, with Closing and Summary most frequently absent. Half of consultations (40/78) did not include phases in the predicted order, with intertwined phases commonly observed. CONCLUSIONS: In this standardised setting, doctors created variable consultation structures, typically omitting phases involving consolidation and agreement of plans going forward. PRACTICE IMPLICATIONS: The method enables visualisation and comparison of consultation structure. The findings pose questions about the alignment of practice with educational guidance and the opportunities afforded to patients to actively engage in consultations.

Patient autonomy in the consultation: How signalling structure can facilitate patient-centred care.

OBJECTIVE: To identify types and functions of doctors' verbal signalling behaviours used to share consultation structure with patients. METHOD: Doctors' verbal utterances signalling what would happen in the consultation were identified by two independent raters from transcripts of 78 simulated consultations from a postgraduate examination for physicians. In total, 974 behaviours were categorised as informing, inviting or instructing. Principles adopted from Speech Act Theory and Conversation Analysis were used to examine their function from their literal meaning and use in context. RESULTS: Signalling behaviours to inform were most frequent, particularly 'signposts', with less informative signalling behaviours also found ('posts without signs' and 'signs without posts'). Behaviours to invite involvement offered limited choice. Doctors also instructed the patient in what to do (behaviour) or not to do (emotion). Behaviours signalled more 'micro-level' changes than broader consultation aims. Signalling behaviours carried roles beyond their literal meaning ('hyperfunctions') and were combined ('stacked'), often seen deflecting the conversation away from patient concerns. CONCLUSION: Doctors use a variety of verbal signalling behaviours with multiple functions. As well as sharing information, these behaviours regulate patient agency in the consultation. PRACTICE IMPLICATIONS: Doctors' signalling behaviours may play an important role in facilitating or inhibiting patient autonomy.

Development of microdialysis methodology for interstitial insulin measurement in rodents.

INTRODUCTION: Accurate assessment of muscle insulin sensitivity requires measurement of insulin concentration in interstitial fluid (ISF), but has proved difficult. We aimed to optimise measurement of ISF insulin concentrations in rat muscles in vivo using microdialysis. METHODS: Factorial experimental design experiments were performed in vitro to determine optimal conditions for insulin recovery with microdialysis probes. These conditions were tested in vivo, adjusted appropriately and used in lean and obese Zucker rats to compare ISF insulin concentrations basally and during hyperinsulinaemic-euglycaemic (HE) clamp. RESULTS: Optimal conditions in vivo were: a 100kDa microdialysis probe inserted in muscle, perfused with 1% BSA, 1.5mM glucose in 0.9% sodium chloride at 1µl/min. Samples were collected into siliconised glass microvials. As a reference for insulin, we established a protocol of inulin infusion, beginning at -80min and reaching equilibrium within 60min. HE clamp, beginning at 0min, increased ISF insulin concentration from 122±56 basally to 429±180pmol/l (P<0.05) in lean rats and from 643±165 to 1087±243pmol/l (P=0.07) in obese rats; ISF insulin concentrations were significantly higher throughout in obese rats. The difference between ISF and plasma insulin concentration (ISF:plasma ratio) was substantially higher in obese rats, but fell to similar values in obese and lean rats during HE clamp. DISCUSSION: Optimising insulin recovery with microdialysis allowed accurate measurement of basal ISF insulin in muscle of lean and obese Zucker rats and indicates insulin transport across capillaries is impaired in obese rats, basally and during hyperinsulinaemia.