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Background

This study aimed to examine: (a) characteristics associated with long-term opioid use and (b) characteristics associated with problematic opioid use, here defined as prescription opioid use disorder (P-OUD), in patients referred to specialised pain care.

Methods

This cross-sectional study utilised baseline data from a clinical chronic pain cohort. Eligible participants included adults > 18 years old, not undergoing cancer treatment, had pain > 3 months, and had been referred to a specialised pain care centre in Sweden. Bivariate logistic regression and multivariable logistic regression with forward selection were used to examine the associations between biopsychosocial variables and either long-term opioid use or P-OUD.

Results

Of the 339 patients included, 194 (57%) were using opioids, 159 (47%) had long-term opioid use (> 90 days), and 34 (21% of those with long-term opioid use) had P-OUD. Longer pain duration, unemployment, more pain catastrophising, lower health-related quality of life, and worse balance increased the likelihood of long-term opioid use. Long-term use of high doses was associated with a greater prevalence of psychiatric and cognitive-behavioural problems compared to long-term use at low to moderate doses. Long-term opioid use, younger age, trauma exposure, more pain catastrophising, and fear of movement increased the likelihood of P-OUD.

Conclusions

Our results demonstrate the importance of identifying and treating salient factors that may sustain both the pain condition and long-term opioid use. Many of the biopsychosocial variables associated with long-term opioid use and P-OUD can be addressed within interdisciplinary pain management and rehabilitation programmes.

Significance

This study is part of the U-PAIN cohort study on a clinical sample from a highly specialised pain centre in Sweden. It is based on a deep and thorough characterisation of patients referred to the clinic to evaluate risks and benefits of opioid therapy in chronic pain. It adds valuable information on the complexity of opioid therapy in chronic pain; the results highlight the need for interdisciplinary multimodal evaluation and treatment.

Background: This study aimed to examine: (a) characteristics associated with long-term opioid use and (b) characteristics associated with problematic opioid use, here defined as prescription opioid use disorder (P-OUD), in patients referred to specialised pain care.

Methods: This cross-sectional study utilised baseline data from a clinical chronic pain cohort. Eligible participants included adults > 18 years old, not undergoing cancer treatment, had pain > 3 months, and had been referred to a specialised pain care centre in Sweden. Bivariate logistic regression and multivariable logistic regression with forward selection were used to examine the associations between biopsychosocial variables and either long-term opioid use or P-OUD.

Results: Of the 339 patients included, 194 (57%) were using opioids, 159 (47%) had long-term opioid use (> 90 days), and 34 (21% of those with long-term opioid use) had P-OUD. Longer pain duration, unemployment, more pain catastrophising, lower health-related quality of life, and worse balance increased the likelihood of long-term opioid use. Long-term use of high doses was associated with a greater prevalence of psychiatric and cognitive-behavioural problems compared to long-term use at low to moderate doses. Long-term opioid use, younger age, trauma exposure, more pain catastrophising, and fear of movement increased the likelihood of P-OUD.

Conclusions: Our results demonstrate the importance of identifying and treating salient factors that may sustain both the pain condition and long-term opioid use. Many of the biopsychosocial variables associated with long-term opioid use and P-OUD can be addressed within interdisciplinary pain management and rehabilitation programmes.

Background The transient receptor potential cation channel subfamily V1 (TRPV1) receptor is an important factor in pain transmission. The present Phase 2a study investigated the effect on evoked pain and safety of a topically administered TRPV1-antagonist (ACD440 Gel) in patients with chronic peripheral neuropathic pain (PNP).Methods This was an exploratory, randomized, placebo-controlled double-blind crossover study in patients with probable or definite PNP demonstrating sensory hypersensitivity, assessed as evoked pain on suprathreshold sensory stimulation, i.e. hyperalgesia. The aetiologies included a mix of postherpetic neuralgia, postoperative neuropathic pains, and chemotherapy-induced pain. Patients administered ACD440 Gel twice daily onto the painful area(s) for 7 days. Primary endpoint was hyperalgesia to brush, cold, heat, and pinprick. Secondary endpoints included spontaneous pain and Neuropathic Pain Symptom Inventory Questionnaire (NPSI). Due to a significant period effect, a post hoc analysis was conducted, including only period 1 data, i.e. a parallel group comparison.Results Fourteen patients were enrolled and completed the study. ACD440 Gel reduced pain intensity evoked by a 40 degrees C thermoroller stimulus in heat hyperalgesic patients, by ACD440 from median 6 (IQR 4.75, 7.75) to 1.5 (IQR 0.75, 2.25), i.e. by -5.0 (95%CI -11.2, 1.2) vs placebo from median 4 (IQR 3.5, 5.0) to median 5.0 (IQR 4.5, 6.5), i.e. by 1.3 (95%CI -1.5, 4.2), p = 0.029. There were no adverse events induced by study treatment. Evoked mechanical hyperalgesia and brush allodynia were not significantly affected, p = 0.07.Conclusion ACD440 Gel demonstrated a significant analgesic effect on thermally evoked pain, especially in suprathreshold heat pain. This is congruent with an attenuation of thermal hyperalgesia in chronic neuropathic pain patients with C-fibre mediated pain, while there was no effect on evoked pain related to A beta and A delta stimuli. The results support further clinical development in patients with thermally induced C-fibre mediated pain.

Purpose

To study patient safety in third molar surgery, where two different doses of S-ketamine were administered for pain relief and compared to a placebo (saline). The primary focus was capillary oxygen saturation of the blood (SpO2) and secondarily, alterations in respiratory rate, blood pressure, pulse or adverse events.

Methods

One hundred and sixty-eight subjects were included in a randomised, placebo-controlled, double-blind trial. The two subanaesthetic study drugs were low-dose S-ketamine (0.125 mg/kg) and high-dose S-ketamine (0.25 mg/kg). Every patient was sedated with midazolam prior to infusion of the investigational drug. The teeth were surgically removed according to a routine clinical procedure, under local anaesthesia.

Results

Primary end-point for the safety aspects was capillary oxygen saturation (SpO2) after administration of the investigational drug was finished. A significant difference was found between the placebo and the high-dose group at that point (p = .021), with a decrease of saturation in the high-dose group. The lowest saturation and the number of registrations of SpO2 <90% did not show any difference between groups. Oxygen supplementation was given in circa 40% of the cases with no differences between the intervention groups. No other significant differences between groups regarding saturation or respiratory rate were noted.

Conclusion

In this study, it was safe to use adjunct preoperative single-dose intravenous S-ketamine 0.25 mg/kg body weight for pain relief, in midazolam-sedated patients receiving third molar surgery. There were no serious adverse events or symptoms of overdose nor any clinically relevant effects on circulatory or respiratory parameters.

Current research indicates that spinal cord stimulation (SCS) has a positive short-term impact on outcomes, such as quality of life, pain, and productivity in patients with chronic neuropathic pain. However, there is a need for studies on larger population samples. This study used data from Swedish national registers to analyze change and predictors of sick leave and disability pension 2 years before and after SCS treatment. Patients with SCS implanted between 2006 and 2017, and a reference group consisting of 5 individuals matched to each SCS patient without replacement with respect to age, sex, and region of residence, were included. A difference-in-difference approach was used to compare the average change (2 years after treatment vs 2 years before treatment) in net disability days and indirect cost related to disability days for the SCS group, compared with the average change for the reference group. The results showed that SCS treatment in Sweden is associated with a decrease of 21 disability days and consequent decrease in indirect cost of euro4127 in working age patients. Large work loss prior to index date was also demonstrated (average 214 days before 1 year), indicating a significant burden on the patient, employers, and the society at large. The number of disability days varied considerably depending on age, sex, socioeconomic variables, and comorbidities; however, the effect of SCS seemed to have little association with patient characteristics. This economic benefit needs to be considered, as well as the clinical outcome, when evaluating the full societal value of SCS.

Background

In most cases, a combination of paracetamol and ibuprofen are the optimal treatment for postoperative pain in third molar surgery. If stronger analgesia is required, opioids are traditionally administered. In day-case, surgery; however, opioids should be avoided. Thus, the anaesthetic agent S-ketamine in analgesic doses might be preferred.

Methods

The study was designed as a randomized placebo-controlled double-blind clinical trial. The study enrolled healthy subjects according to the American Society of Anaesthesiologists classification; I or II (ASA), aged 18 to 44 years, with a body weight between 50 and 100 kg. The patients were randomized into three groups where two doses of S-ketamine were compared (high: 0.25 mg/kg or low: 0.125 mg/kg) with placebo (saline).

Results

A primary outcome of the study was that VAS at 4 h postoperatively, showed no significant difference between the placebo and high-dose S-ketamine group or in the low-dose group. We found a significant difference between the groups for the first 24 h, with a lower VAS-score in the high-dose S-ketamine group. The time to when 50% had taken their first rescue medication was 12 min later in the high-dose ketamine group.

Conclusions

Pre-emptive S-ketamine 0.25 mg/kg gave a global significant reduction of pain by VAS during the first 24 h postoperatively. The time from end of surgery to first rescue medication were longer in the high-dose ketamine group compared to both low-dose ketamine and placebo groups.

Objective: To evaluate the construct validity and internal consistency of the Work Ability Index (WAI) in patients with chronic pain in secondary and tertiary care.

Methods: Cross-sectional study based on 200 patients with chronic pain (> 3 months), with a final sample of 118 participants, 18–64-years-old. Construct validity was assessed by exploratory factor analysis for the structural validity of the WAI, and by correlating the WAI with EuroQol EQ-5D, Brief Pain Inventory pain severity and interference, Patient Health Questionnaire and Generalized Anxiety Disorder scales. The study also assessed the discriminant validity of the WAI for occupational status, and the validity of the single-item work ability score. Reliability was assessed by internal consistency.

Results: A single-factor model of WAI was supported. Internal consistency was good. Moderate correlations were found, except for Brief Pain Inventory pain severity, where the correlation was weak; hence, both convergent and divergent validity of the WAI were supported. The work ability score correlated strongly with the total WAI, and the discriminant validity for both was good.

Conclusion: In patients with chronic pain in specialized care, the WAI and the work ability score displayed acceptable construct validity and internal consistency, supporting their use in a clinical context and research.

Introduction: Despite advancements in implanted hardware and development of novel stimulation paradigms in Spinal Cord Stimulation (SCS), real world evidence suggests a large variation in patient reported outcomes and a proportion of patients are later explanted due to loss of analgesia. Possible predictors for outcome have been explored in smaller short-term evaluations, but few clinically applicable robust measures for long term outcome have emerged.

Methods: We performed a comprehensive retrospective study based on an assembled patient-level aggregated database from multiple local and national registries in Sweden. Variables associated with risk of explantation (due to insufficient analgesia) and analgesic effect was analyzed using a Cox regression analysis and an ordered logit regression model, respectively.

Results: We found the accumulated risk of explantation due to loss of analgesia to be 10% and 21% at two and ten years follow up, respectively. The use of 10 kHz spinal cord stimulation (compared with Tonic waveform; p = 0.003), and being 60 years or older (reference 18-40 years; p = 0.003) were associated with an increased risk of explantation.At a mean follow up at 1 year, 48% of patients reported a pain intensity reduction from baseline of at least 30%. Secondary (p = 0.030) and post-secondary (p = 0.001) education (compared with primary education) was associated with an increased probability of successful patient reported outcomes.Results:We found the accumulated risk of explantation due to loss of analgesia to be 10% and 21% at two and ten years follow up, respectively. The use of 10 kHz spinal cord stimulation (compared with Tonic waveform; p = 0.003), and being 60 years or older (reference 18-40 years; p = 0.003) were associated with an increased risk of explantation.At a mean follow up at 1 year, 48% of patients reported a pain intensity reduction from baseline of at least 30%. Secondary (p = 0.030) and post-secondary (p = 0.001) education (compared with primary education) was associated with an increased probability of successful patient reported outcomes.

Conclusion: This study suggests that a higher educational level and being employed are associated with successful treatment outcome in patients with chronic pain treated with SCS in Sweden.

Effective interventions are needed for return-to-work (RTW) for individuals with chronic pain on long-term sick leave. In this study, a behavioral medicine physiotherapy protocol was systematically replicated and added to workplace components. The intervention was evaluated for fidelity and effects on target activities and work ability. A single-case experimental design was used with five participants. Daily and weekly ratings of personalized target activities at work as well as work ability were carried out throughout the study period of 26-28 weeks. Effects of the behavioral medicine physiotherapy intervention were evaluated for each individual using visual analysis of displayed graphs and quantitative non-overlap methods. Goal achievement for target activities was reviewed. Three participants completed the intervention. The results indicated an effect from the behavioral medicine physiotherapy intervention on task-specific self-efficacy for target activities, but no consistent effect on experience of target activities or work ability. All three participants had increased function in target activities in line with pre-defined goals. Fidelity to the intervention manual was good. Behavioral medicine physiotherapy can be successfully adapted to work disability and was here replicated in an RTW context for individuals with chronic pain. The intervention protocol should be further evaluated in large-scale studies.

Valid assessment of pain is essential in daily clinical practice to enhance the quality of care for the patients and to avoid the risk of addiction to strong analgesics. The aim of this paper is to find a method for objective and quantitative evaluation of pain using multiple physiological markers. Data was obtained from healthy volunteers exposed to thermal and ischemic stimuli. Twelve subjects were recruited and their physiological data including skin conductance, heart rate, and skin temperature were collected via a wrist-worn sensor together with their selfreported pain on a visual analogue scale (VAS). Statistically significant differences (p < 0.01) were found between physiological scores obtained with the wearable sensor before and during the thermal test. Test-retest reliability of sensor-based measures was good during the thermal test with intraclass correlation coefficients ranging from 0.22 to 0.89. These results support the idea that a multi-sensor wearable device can objectively measure physiological reactions in the subjects due to experimentally induced pain, which could be used for daily clinical practice and as an endpoint in clinical studies. Nevertheless, the results indicate a need for further investigation of the method in real-life pain settings.