A retrospective study evaluating the trend of opioid prescribing in low back pain at a UK teaching hospital

Introduction: Current data suggest that the chronic use of strong opioids in low back pain (LBP) is increasing. There is evidence for the use of opioids in the initial management of LBP, but the efficacy in the long term is unknown. This article intends to examine the use of opioids in patients with chronic LBP over a period of three doctor-led clinics.Methods: Single-center retrospective cohort study following 200 patients through the pain clinic at a UK teaching hospital for more than two clinic visits, up to a maximum of three. Data concerning demographics, pain scores, medication changes, and clinic outcome.Results: Data collected showed that there was a significant correlation between baseline morphine equivalent amount (MEA) and final clinic MEA; initial pain scores and final clinic MEA; cause of LBP and final clinic LBP; and traumatic LBP and absolute change in MEA. There was no association between number of physical interventions and MEA. The sample also showed an average absolute change in MEA by 2.93 ± 57.86 mg. The proportion of patients with a MEA of 50 mg/d increased from 24 to 29 percent. The proportion of patients on opioids at least one opioid increased by 10 percent.Conclusions: Significant predictors of final clinic MEA were initial pain scores, baseline MEA, and the cause of LBP. Duration of pain was a poor predictor of MEA. There was no association between MEA and number of interventions. In this cohort, the trend seems to be increasing the number and dose of opioids in patients with LBP.

Effects of a diuretic regimen on body weight and echocardiographic parameters of the tricuspid valve in patients scheduled for transcatheter tricuspid annuloplasty

Background Echocardiographic severity of tricuspid regurgitation is known to be highly variable and strongly related to the volume status of the individual patient. Interventional therapies for tricuspid valve repair or replacement are dependent on reliable measurements in order to select the appropriate device size. Purpose In patients scheduled for transcatheter tricuspid valve annuloplasty, we sought to evaluate the effects of a diuretic regimen started at the screening visit on body weight and tricuspid valve dimensions at the time point of transcatheter intervention. Methods After successful screening for transcatheter tricuspid annuloplasty, an individualized intensified diuretic regimen was initiated in 15 patients. At baseline and at the timepoint of the intervention, body weight and 3D echocardiographic dimensions of the tricuspid valve were documented and compared. Results The cohort comprised 6 males and 9 females (mean age 77±7 years) with severe or higher degree functional tricuspid regurgitation. In all patients not more than mild pulmonary artery hypertension was present (PaP mean 29±5 mmHg). The interval between the screening visit and the timepoint of the procedure was 64±50 days. At baseline mean body weight was 72±12 kg. In 11 patients a reduction of the body weight could be achieved, with a median weight reduction of 2.2 kg (min/max 1.2/6.4 kg). Overall, the average relative reduction of the tricuspid annulur perimeter was 13% (p<0,001), of the tricuspid valve area 2.7% (n.s.), the anterseptal diameter 3.3% (n.s.), while the bicommissural diameter remained almost unchanged (0.4%; n.s.). The average predicted required band length changed by only 1.5% (n.s.). The strongest correlations were found between the absolute change in body weight and the change of the tricuspid valve area (r=0.48), relative change in body weight and relative change of tricuspid valve area (r=0.52), absolute change in body weight and absolute change in predicted band length (r=0.48), and relative changes of the respective variables (r=0.52). More importantly, in 13 out of 15 patients the band size which would have been selected was identical between the screening and the annuloplasty procedure. Only in two patients a smaller device was implanted than predicted at the screening visit. Conclusion Instituting a diuretic therapy in candidates for transcatheter tricuspid annuloplasty prior to the procedure helps to keep tricuspid valve dimensions in a stable range. Changes in body weight in patients with functional tricuspid regurgitation are correlated to changes of tricuspid valve dimensions. FUNDunding Acknowledgement Type of funding sources: None.

Derivation and validation of a novel 3-hour pathway for the observe-zone of the ESC 0/1h-algorithm

Background The latest non-ST elevation myocardial infarction (NSTEMI) guidelines from the European Society of Cardiology (ESC) recommend a 3h cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-algorithm; however, no specific cut-off for further triage is endorsed. Purpose To derive and internally, as well as externally, validate a novel 3-hour pathway for the observe-zone of the ESC 0/1h-algorithm. Methods In an ongoing multicentre international diagnostic study, we prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of myocardial infarction (MI). Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI, based on complete cardiac work-up including cardiac imaging, serial high sensitivity cardiac troponin T (hs-cTnT) sampling and 90-day follow-up information. High sensitivity-cTnT concentrations were measured at presentation and after 1 and 3 hours. The primary outcome was safety, quantified by the sensitivity and NPV for early rule out of NSTEMI. External validation was performed in an independent multicentre international study. Results Among 2076 eligible patients, application of the ESC 0/1h-algorithm triaged 1512 patients (72.8%) to either rule-out or rule-in of NSTEMI, remaining 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence 120/564 patients, 21.3%). The novel derived 3h-pathway for the observe-zone patients ruled-out NSTEMI with a 3h hs-cTnT concentration <15 ng/L and a 0/3h-hs-cTnT absolute change <4 ng/L, triaging 138 patients (25%) towards rule-out, resulting in a sensitivity of 99.2% (95% CI 96.0–99.9) and a NPV of 99.3% (95% CI 95.4–99.9). A 0/3h-hs-cTnT absolute change ≥6 ng/L ruled-in 63 patients (11.2%), resulting in a specificity of 98% (95% CI 96.2–98.9) and a PPV of 85.7% (95% CI75.0–92.3). The novel 3h-pathway reduced the number of patients in the observe zone by 36%, and the number of T1MI by 50% (Figure 1). Findings were confirmed in both internal and external validation. Conclusions A novel derived pathway combining a 3h hs-cTnT concentration <15 ng/L and a 0/3h absolute change <4 ng/L allowed to very safely rule-out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-algorithm. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Swiss Heart FoundationThe Swiss National Science Foundation Figure 1

Bipolar Radiofrequency Neurotomy of the Genicular Nerves for Chronic Pain Due to Knee Osteoarthritis

Background: The current treatments for chronic knee osteoarthritis (OA), a disabling and costly healthcare condition in the United States, vary in their level of supporting evidence. Although total knee replacement is one of the best-supported interventions, its associated risks should not be taken lightly, especially in older patients with comorbidities. Genicular nerve block with subsequent genicular nerve radiofrequency neurotomy (GN-RFN) has emerged as a promising intervention for refractory pain in knee OA. Purposes/Questions: We sought to assess the pain and functional outcomes of genicular nerve bipolar radiofrequency neurotomy (B-RFN) for the treatment of chronic pain due to knee OA. Methods: A total of 21 patients who underwent unilateral genicular nerve B-RFN after positive diagnostic genicular nerve block (50% or greater pain relief) treated between July 2018 to December 2018 were included. Pain numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were collected at baseline, 3 months, and 6 months post-B-RFN. Changes at each time point were compared to baseline scores using paired sample t tests. Results: At 3 months, 62% of patients had a greater than 50% improvement in NRS scores and 57% of patients had a greater than 50% improvement in WOMAC scores. At 6 months, 81% of patients had a greater than 50% improvement in NRS scores and 67% had a greater than 50% improvement in WOMAC scores. The absolute change in mean NRS (± standard deviation) at 6 months went from 7.5 ± 1.9 to 2.5 ± 1.2. The absolute change in mean WOMAC scores at 6 months went from 46.9 ± 8.0 to 19.0 ± 6.2. Conclusion: Of 21 patients, 14 (67%) saw greater than 50% improvements in both NRS and WOMAC scores at 6 months after genicular nerve B-RFN. Further prospective studies are needed to determine the selection criteria of patients most likely to benefit from this procedure.

Temporal metabolic response to mRNA COVID-19 vaccinations in oncology patients

Background mRNA COVID-19 vaccines are known to provide an immune response seen on FDG PET studies. However, the time course of this metabolic response is unknown. We here present a temporal metabolic response to mRNA COVID-19 vaccination in oncology patients undergoing standard of care FDG PET. Methods 262 oncology patients undergoing standard of care FDG PET were included in the analysis. 231 patients had at least one dose of mRNA COVID-19 vaccine while 31 patients had not been vaccinated. The SUVmax of the lymph nodes ipsilateral to the vaccination was compared to the contralateral to obtain an absolute change in SUVmax (ΔSUVmax). Results ΔSUVmax was more significant at shorter times between FDG PET imaging and COVID-19 mRNA vaccination, with a median ΔSUVmax of 2.6 (0–7 days), 0.8 (8–14 days), and 0.3 (> 14 days), respectively. Conclusion Consideration should be given to performing FDG PET at least 2 weeks after the COVID-19 vaccine.

Novel Criteria for the Observe-Zone of the ESC 0/1h-hs-cTnT Algorithm

Background: The non-ST elevation myocardial infarction (NSTEMI) guidelines of the European Society of Cardiology (ESC) recommend a 3h cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-algorithm; however, no specific cut-off for further triage is endorsed. Recently, a specific cut-off for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7ng/L) was proposed warranting external validation. Methods: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI, based on complete cardiac work-up, cardiac imaging and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1h and 3h. The objective was to externally validate the proposed cut-off, and if necessary, derive and internally as well as externally validate novel 0/3h-criteria for the observe-zone of the ESC 0/1h-hs-cTnT-algorithm in an independent multicenter cohort. Results: Among 2076 eligible patients, application of the ESC 0/1h-hs-cTnT-algorithm triaged 1512 patients (72.8%) to either rule-out or rule-in of NSTEMI, remaining 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of <7ng/L triaged 517 patients (91.7%) towards rule-out, resulting in a sensitivity of 33.3% (95%CI 25.5-42.2), missing 80 patients with NSTEMI, and ≥7ng/L triaged 47 patients towards rule-in (8.3%), resulting in a specificity of 98.4% (95%CI 96.8-99.2). Novel derived 0/3h-criteria for the observe-zone patients ruled-out NSTEMI with a 3h hs-cTnT concentration <15 ng/L and a 0/3h-hs-cTnT absolute change <4 ng/L, triaging 138 patients (25%) towards rule-out, resulting in a sensitivity of 99.2% (95%CI 96.0-99.9), missing 1 patient with NSTEMI. A 0/3h-hs-cTnT absolute change ≥6 ng/L triaged 63 patients (11.2%) towards rule-in, resulting in a specificity of 98% (95%CI 96.2-98.9) Thereby, the novel 0/3h-criteria reduced the number of patients in the observe zone by 36%, and the number of T1MI by 50%. Findings were confirmed in both internal and external validation. Conclusions: A combination of a 3h hs-cTnT concentration (<15 ng/L) and a 0/3h absolute change (<4 ng/L) is necessary to safely rule-out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnT-algorithm. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT00470587

Estimating the minimum important difference in the DEMQOL instrument in people with dementia

Purpose The Dementia-Related Quality of Life (DEMQOL) measure and the DEMQOL-Utility Score (DEMQOL-U) are validated tools for measuring quality of life (QOL) in people with dementia. What score changes translate to a clinically significant impact on patients’ lives was unknown. This study establishes the minimal important differences (MID) for these two instruments. Methods Anchor-based and distribution-based methods were used to estimate the MID scores from patients enrolled in a randomised controlled trial. For the anchor-based method, the global QOL (Q29) item from the DEMQOL was chosen as the anchor for DEMQOL and both Q29 and EQ-5D for DEMQOL-U. A one category difference in Q29, and a 0.07 point difference in EQ-5D score, were used to classify improvement and deterioration, and the MID scores were calculated for each category. These results were compared with scores obtained by the distribution-based methods. Results A total of 490 people with dementia had baseline DEMQOL data, of these 386 had 8-month data, and 344 had 12-month DEMQOL data. The absolute change in DEMQOL for a combined 1-point increase or decrease in the Q29 anchor was 5.2 at 8 months and 6.0 at 12 months. For the DEMQOL-U, the average absolute change at 8 and 12 months was 0.032 and 0.046 for the Q29 anchor and 0.020 and 0.024 for EQ-5D anchor. Conclusion We present MID scores for the DEMQOL and DEMQOL-U instruments obtained from a large cohort of patients with dementia. An anchored-based estimate of the MID for the DEMQOL is around 5 to 6 points; and 0.02 to 0.05 points for the DEMQOL-U. The results of this study can guide clinicians and researchers in the interpretation of these instruments comparisons between groups or within groups of people with dementia. Trial Registration Number and date of registration: ISRCTN17993825 on 11th October 2016.

Modelling Feedback Effects on the Production of Short Time Intervals

People produced time intervals of 500 to 1250 ms, with accurate feedback in ms provided after each production. The mean times produced tracked the target times closely, and the coefficient of variation (standard deviation/mean) declined with increasing target time. The mean absolute change from one trial to another, and its standard deviation, measures of trial-by-trial change, also increased with target time. A model of feedback was fitted to all four measures. It assumed that the time produced resulted from a combination of a scalar timing process and a non-timing process. Although the non-timing process was on average invariant with target time, the timing process was assumed to be sensitive to feedback, in two different ways. If the previous production was close to the target the model repeated it (a repeat process), but if it was further away the next production was adjusted by an amount related to the discrepancy between the previous production and the target (an adjust process). The balance between the two was governed by a threshold, which was on average constant, and it was further assumed that the relative variability of the repeat process was lower than that of the adjust process. The model produced output which fitted three of the four measures well (average deviation of 3 or 4%) but fitted the standard deviation of change less well. Reducing the magnitude of the non-timing process produced output which conformed approximately to scalar timing, and the model could also mimic data resulting from the provision of inaccurate feedback.

Exercise-Induced Alterations in Phospholipid Hydrolysis, Airway Surfactant and Eicosanoids and their Role in Airway Hyperresponsiveness in Asthma

The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (n=18) and bronchoalveolar lavage (BAL) fluid (n=11) were obtained before and after exercise challenge in asthmatic subjects. Samples were analyzed for phospholipid structure, surfactant function and levels of eicosanoid and secreted phospholipase A2 group 10 (sPLA2-X). A primary epithelial cell culture model was used to model effects of osmotic stress on sPLA2-X. Exercise challenge resulted in increased surfactant degradation, phospholipase activity, and eicosanoid production in sputum samples of all patients. Subjects with EIB had higher levels of surfactant degradation and phospholipase activity in BAL fluid. Higher basal sputum levels of cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) were associated with direct AHR and both the post-exercise and absolute change in CysLTs and PGD2 levels were associated with EIB severity. Surfactant function was either abnormal at baseline or became abnormal after exercise challenge. Baseline levels of sPLA2-X in sputum and the absolute change in amount of sPLA2-X with exercise were positively correlated with EIB severity. Osmotic stress ex vivo resulted in movement of water and release of sPLA2-X to the apical surface. In summary, exercise challenge promotes changes in phospholipid structure and eicosanoid release in asthma, providing two mechanisms that promote bronchoconstriction, particularly in individuals with EIB who have higher basal levels phospholipid turnover.