Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Pre-registered controlled comparison of auditory function reveals no difference between hospitalised adults with and without COVID-19.

OBJECTIVE: Several viruses are known to have a negative impact on hearing health. The global prevalence of COVID-19 means that it is crucial to understand whether and how SARS-CoV2 affects hearing. Evidence to date is mixed, with studies frequently exhibiting limitations in the methodological approaches used or the populations sampled, leading to a substantial risk of bias. This study addressed many of these limitations. DESIGN: A comprehensive battery of measures was administered, including lab-based behavioural and physiological measures, as well as self-report instruments. Performance was thoroughly assessed across the auditory system, including measures of cochlear function, neural function and auditory perception. Hypotheses and analyses were pre-registered. STUDY SAMPLES: Participants who were hospitalised as a result of COVID-19 (n = 57) were compared with a well-matched control group (n = 40) who had also been hospitalised but had never had COVID-19. RESULTS: We find no evidence to support the hypothesis that COVID-19 is associated with deficits in auditory function on any auditory test measure. Of all the confirmatory analyses, only the self-report measure of hearing decline indicated any difference between groups. CONCLUSION: Results do not support the hypothesis that COVID-19 infection has a significant long-term impact on the auditory system.

Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients.

Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07-5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45-2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.

Survey of the use of oesophageal and precordial stethoscopes in current paediatric anaesthetic practice.

BACKGROUND: The aim of the study was to examine the use of oesophageal and precordial stethoscopes for monitoring in current paediatric anaesthetic practice in the UK and Ireland. METHODS: A postal survey of members of the Association of Paediatric Anaesthetist of Great Britain and Ireland was undertaken. RESULTS: One hundred and forty-five questionnaires were returned with a response rate of 67.4%. Some 35.2% of anaesthetists never use an oesophageal or precordial stethoscope and the majority of the remaining 64.8% use one in less than one-third of their practice. CONCLUSION: Use of the stethoscope as a continuous monitor has decreased and most anaesthetists feel it has been superseded by other monitoring. However, almost one-third of anaesthetists recorded critical incidents they had been involved with where an oesophageal or precordial stethoscope detected the incident early. Complications of these monitoring devices were rare and the main factors limiting their use was the presence of better monitoring, such as pulse oximetry and capnography, and lack of availability.

Patient-controlled alfentanil. Target-controlled infusion for postoperative analgesia.

We have compared the opioid effects of a patient-demand, target-controlled infusion of alfentanil (n = 10), with patient-controlled bolus administration of morphine (n = 10) following major spinal surgery in Chinese patients aged from 11 to 67 years. The same general anaesthesia regimen was used in all patients. One group of patients were given intra-operative morphine analgesia followed by postoperative intravenous morphine patient-controlled analgesia, while the other group received an intra-operative target-controlled infusion of alfentanil. Following surgery, the alfentanil group were given control of a handset and were able to increase the target alfentanil plasma level in 5 ng.ml-1 increments with a 2-min lockout interval. If analgesia was not demanded within a 15-min period, the computer reduced the target concentration by 5 ng.ml-1. All patients had continuous pulse oximetry monitoring and hourly recording of pain, sedation, nausea scores and respiratory rate. Patients receiving alfentanil had the target concentration noted hourly and four blood samples taken during the first 24 h for measurement of plasma alfentanil concentrations by high performance liquid chromatography. The alfentanil infusion system was equally effective as an analgesic technique when compared with morphine patient-controlled analgesia. There were no hypoxaemic episodes (oxygen saturation < 94%), no difference in sedation scores and the incidence of nausea (30%) was the same in both groups. There was a significantly (p < 0.001) lower respiratory rate in the alfentanil group compared with patients receiving morphine at, clinically assessed, equianalgesia. The predicted plasma alfentanil concentrations increased rapidly from about 30 ng.ml-1 during the first 4 h to around 100 ng.ml-1 at the end of the 24-h study period. The precision of the target-controlled infusion system was 75.4% and the mean prediction error (bias) 58.1%, suggesting an underestimation of the measured alfentanil concentrations by the alfentanil infusion system in these Chinese patients.

Peri-operative administration of rectal diclofenac sodium. The effect on renal function in patients undergoing minor orthopaedic surgery.

In a randomized, double-blind study, we administered placebo and diclofenac sodium 100 mg suppositories 1 h pre-operatively and on the first post-operative morning to 22 adult patients undergoing minor orthopaedic surgery. A standardized post-operative intravenous fluid regimen was instituted until oral fluids were tolerated. Renal function was assessed pre-operatively, and on the first and second post-operative days by the measurement of urine output, creatinine, urea, sodium, potassium and NAG (N-acetyl-b-D-glucosaminidase) levels and serum creatinine, urea, sodium and potassium concentrations. On the first post-operative day, the diclofenac group demonstrated a reduced urinary sodium excretion. On the second post-operative day, a reduced urinary NAG/creatinine ratio was observed in the diclofenac group when compared to placebo. We conclude that peri-operative administration of diclofenac causes changes in renal function consistent with prostaglandin inhibition on the first post-operative day but had no lasting adverse effects in this group of patients. Our results reinforce the need for caution when administering this drug in the context of pre-existing renal impairment.

Premedication with oral midazolam in children--an assessment of psychomotor function, anxiolysis, sedation and pharmacokinetics.

We studied 30 children, aged 4 to 12 years, undergoing elective circumcision, premedicated with midazolam 0.5 mg.kg-1 and atropine 0.02 mg.kg-1 by mouth. A modified postbox test and the coding component of the Wechsler intelligence scale (WISC-R) was used to assess the preoperative effect of premedication on psychomotor function. Mood and sedation were also scored and related to serum midazolam concentrations. The children showed a significant decline in psychomotor performance 30 and 60 minutes after premedication when compared with their best unmedicated performance recorded the previous evening. This decline in psychomotor performance was only weakly associated with serum midazolam concentrations (r = 0.1). The postbox toy ratio is a suitable measurement of psychomotor performance in children because of its simplicity and ease of use in the clinical environment, although it may suffer the "test-retest" limitations of similar types of assessment. The sedative and anxiolytic effects of midazolam provide a quiet environment for a smooth induction of anaesthesia.

A comparison of three induction agents in paediatric anaesthesia--cardiovascular effects and recovery.

We studied 30 children undergoing circumcision randomly allocated to receive either thiopentone 4 mg.kg-1, propofol 2.5 mg.kg-1 or midazolam 0.5 mg.kg-1 (n = 10) IV over 30 seconds at induction of anaesthesia. Blood pressure and pulse rate during the first 15 minutes of induction were recorded by a Finapres 2300e and a Cardiocap CM-104, and changes from preinduction baseline compared between the three induction agents and the two recording instruments. Postoperatively, blood levels of the induction agents were measured and recovery from anaesthesia was assessed by clinical criteria, mood and sedation scores and psychomotor performance. The Cardiocap data revealed no statistically significant haemodynamic differences between the three induction agents. Finapres data demonstrated that propofol caused a greater decrease in mean arterial pressure when compared to thiopentone at one minute (P = 0.01) and the MAP remained significantly lower than midazolam at five minutes (P = 0.02), illustrating an advantage of continuous over intermittent non-invasive blood pressure monitoring. The midazolam group took longer to identify themselves compared to both the propofol (P = 0.005) and the thiopentone groups (P = 0.02), but there was no difference in the groups in time to eye-opening. Psychomotor performance on awakening was significantly worse in the midazolam group compared to the propofol (P < 0.03) and thiopentone groups (P < 0.02). Most children had recovered to 80% of their best, practised, unmedicated, preoperative performance four hours after awakening, irrespective of the induction agent administered. Drug blood levels correlated weakly with both methods of psychomotor assessment (r > or = 0.6). Of the three induction agents, thiopentone caused the least haemodynamic perturbation on induction, and anaesthesia induced with midazolam caused the greatest psychomotor impairment on awakening. Within one hour patients in all drug groups were equally awake, co-operative and co-ordinated.

A patient's experience of a new post-operative patient-controlled analgesic technique.

A patient underwent major spinal surgery, twice within a 3 week period. On the first occasion his post-operative pain was managed by conventional morphine patient-controlled analgesia (PCA). After the second procedure his pain was managed by a patient-controlled computer-assisted titration of alfentanil. This provided the opportunity to compare the efficacy of these two drug regimens in the same subject. The results showed comparable quality of analgesia and sedation and similar effects on respiration. However, the patient expressed a preference for morphine PCA.

The effect of premedication on oxygen saturation during the post-premedication period in 20 Chinese children undergoing elective surgery.

Peri-operative continuous pulse oximetric data were studied in healthy Chinese children randomly allocated to receive either pethidine 1 mg kg-1 and atropine 0.02 mg kg-1 intramuscularly 90 min prior to surgery (n = 10), or midazolam 0.5 mg kg-1 and atropine 0.02 mg kg-1 orally, 120 min before surgery (n = 10). Data were collected during the night before surgery, after premedication and for 8 h post-operatively. The pulse oximeter (Nellcor N-200E) output was retrospectively evaluated using Satmaster, a computer programme which permits storage, retrieval, signal evaluation and compilation of oximetric data. There was no significant difference in the frequency, duration, or magnitude ofdesaturation episodes recorded during the post-premedication period compared to the desaturation episodes which occurred in the same child during normal sleep, on the night before surgery. Furthermore, there was no significant difference in the desaturation data between the two premedicant regimens. No child recorded a genuine desaturation less than 80% for longer than 15 s at any time during the study. Neither regimen significantly depressed saturation in otherwise healthy children presenting for minor surgical procedures.

Preoperative and postoperative oxygen saturation in the elderly following spinal or general anaesthesia--an audit of current practice.

We have compared the incidence of preoperative and postoperative oxygen desaturation in 20 elderly patients undergoing dynamic hip screw insertion for fractured neck of femur, allocated randomly to two groups to receive subarachnoid anaesthesia (SA, n = 10) or a general anaesthetic (GA, n = 10). Oximetry data were recorded during the preoperative night and the first 48 hours after surgery using Satmaster. Data associated with zero amplitude signal were automatically invalidated by the software and decreases in SpO2 which were preceded by contemporaneous changes in signal amplitude which conformed to a previously described template were assumed to be artefactual and were discarded from final data analysis. Data demonstrated a wide interpatient variability. However, those patients who desaturated preoperatively continued to do so in the postoperative period. The differences between the preoperative and postoperative oximetry profiles were examined for each patient and demonstrated a significantly longer time spent with SpO2 < 90% in the GA group compared with the SA group, in all the recorded time periods, except on the day of surgery. The SA group showed an improvement in oxygen saturation postoperatively when compared to the preoperative night, spending less time with an SpO2 < 85%. We conclude that the subarachnoid anaesthetic technique was associated with a lower incidence of postoperative oximetry desaturation when compared with general anaesthetic for these elderly patients undergoing repair of fractured neck of femur.

Use of two oximeters to investigate a method of movement artefact rejection using photoplethysmographic signals.

Oxygen haemoglobin saturations and plethysmograph signal amplitudes were recorded from two oximeters placed on the fingers and toes of 10 patients undergoing oesophagectomy, to assess a method of removing motion artefact from saturation recordings. By examining changes in the plethysmograph amplitude that preceded changes in saturation, episodes of desaturation caused by movement artefacts were removed from the data. The reliability of the method was then determined by scrutinizing two concurrent oximetric profiles from each patient. A total of 1600 h of data were evaluated. Desaturations occurring contemporaneously in both oxygen saturation profiles were presumed genuine, whereas a desaturation occurring in only one of the profiles was classified as artefactual. Our method had a sensitivity of 96%, a positive predictive power of 98% and a specificity of 60%. We modified the method to increase specificity and re-evaluated our data. We found that a useful increase in specificity was associated with a considerable decline in sensitivity.

The Finapres 2300e finger cuff. The influence of cuff application on the accuracy of blood pressure measurement.

Blood pressure measurements associated with malapplication of a finger cuff were compared with contemporaneous intra-arterial pressure data in seven volunteers to determine the influence of cuff application on the accuracy of the Finapres 2300e. Systolic readings in all cuff positions differed from arterial line data by more than the recommended standard and tight and loose cuff applications under and over-read respectively, in all subjects. The results show the Finapres to be sensitive to small degrees of finger cuff malapplication which contribute to the bias on direct arterial comparison and limit the reliability of the instrument in clinical practice.