“Opioids are opioids” – a phenomenographic analyses of physicians’ understanding of what makes the initial prescription of opioids become long-term opioid therapy

Abstract Objective: To explore prescribers’ understanding of what makes initial prescription of opioids become long-term-opioid therapy (opioids >90 days). Design: Qualitative study, using phenomenography for data analysis. Methods: Semi-structured interviews conducted by one researcher were used for data collection. Participants were recruited consecutively until categorical saturation was reached. The transcripts were analyzed and categorized by two researchers. A third researcher checked for consistency between the data and the categories. An outcome space was constructed representing the logical relationship between the categories. Setting: Primary, secondary and tertiary care in Sweden. Subjects: Fifteen attending physicians working within the fields of general practice, rehab medicine, orthopedic surgery, neurosurgery, or obstetrics and gynecology. Results: The analysis identified six categories: The addictive opioid, The deserving patient, The ignorant prescriber, The lost patient, The compassionate prescriber, and The exposed prescriber. The differences in conceptions among the categories were clarified through three main contributors related to opioid therapy: prescriber’s characteristics, patient’s characteristics, and the healthcare organization. Conclusion: Opioids were understood as being addictive with long-term use promoting a downward spiral of tolerance and withdrawal driving the pain, leading to continued prescription. Long-term opioid therapy could be justified for patients who improved in function, and who were perceived as trustworthy. Inadequate follow-up of patients, poor training in pain management and addiction medicine, personal attitudes and beliefs about opioids, a perceived professional obligation to treat patients with pain, and lack of collegial support, were factors understood to promote clinically unindicated long-term opioid therapy

A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients

The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest

A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients

The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest

Results from univariate and multivariate analysis of ALS patients compared to controls.

<p>Results from univariate and multivariate analysis of ALS patients compared to controls.</p

ALS Biomarker candidates.

<p>Boxplots showing the CSF levels for follistatin, IL1-alpha and KLK5 for ALS patients and matched controls. The protein levels are compared using the Mann-Whitney U-test and p-values are displayed in the Figures. The limits of detection are indicated by dashed horizontal lines. The y-axes represent Ct-values.</p

Protein variation among the investigated individuals.

<p><b>A) Boxplots showing protein concentrations ranges in CSF from 72 individuals without neurological disorders.</b> The concentration ranges between the upper and lower limits of detection for each marker are shown in grey. The numbers below and above the boxplots show the number of patient samples (out of the total 72) that are outside the detection limits. <b>B) Performance measures for each protein assay.</b> The 1^st, 2^nd (median) and 3^rd quartile values of the robust % CV. The numbers of detectable samples out of a total of 72 samples are found at the bottom line for each marker.</p