Opioid prescribing in the Netherlands during the COVID-19 pandemic: a national register-based study.

OBJECTIVES: The COVID-19 pandemic and related lockdown measures disrupted global healthcare provision, including opioid prescribing. In North America, opioid sales declined while opioid-related deaths increased. In Europe, the effect of the pandemic on prescribing is not yet known. Given the ongoing increase in opioid-related harm and mortality, it is crucial to analyse the impact of the COVID-19 crisis and lockdown measures on opioid prescribing. Therefore, the objective of this study was to characterise opioid prescribing in the Netherlands during the COVID-19 pandemic. DESIGN: A nationwide register-based study characterising opioid prescribing using aggregated insurance reimbursement data. SETTING: Dutch healthcare during the first 2 years of the COVID lockdown. PARTICIPANTS: The whole Dutch population. PRIMARY AND SECONDARY OUTCOME MEASURES: Comparing the number of opioid prescriptions during the pandemic with a prepandemic period using a risk ratio (RR), with separate analysis on the prescription type (first-time or repeat prescription), patients' sex, age and socioeconomic status. We also explored lockdown effects. RESULTS: During the first lockdown, the total number of new opioid prescriptions and prescriptions to young patients (briefly) decreased (RR 0.88, 95% CI 0.88 to 0.89 and RR 0.73, 95% CI 0.70 to 0.75, respectively), but the overall number of opioid prescriptions remained stable throughout the pandemic compared with prepandemic. Women, older patients and patients living in lower socioeconomic areas received more opioids per capita, but the pandemic did not amplify these differences. CONCLUSIONS: The pandemic appears to have had a limited impact on opioid prescribing in the Netherlands. Yet, chronic use of opioids remains an important public health issue.

Perioperative pain management models in four European countries: A narrative review of differences, similarities and future directions.

There is general agreement that acute pain management is an important component of perioperative medicine. However, there is no consensus on the best model of care for perioperative pain management, mainly because evidence is missing in many aspects. Comparing the similarities and differences between countries might reveal some insights into different organisational models and how they work. Here, we performed a narrative review to describe and compare the structures, processes and outcomes of perioperative pain management in the healthcare systems of four European countries using Donabedian's framework as a guide. Our comparison revealed many similarities, differences and gaps. Different structures of acute pain services in the four countries with no common definition and standards of care were found. Protocols have been implemented in all countries and guidelines in some. If outcome is assessed, it is mainly pain intensity, and many patients experiencing more intense pain than others have common risk factors (e.g. preoperative pain, preoperative opioid intake, female sex and young age). Outcome assessment beyond pain intensity (such as pain-related physical function, which is important for early rehabilitation and recovery) is currently not well implemented. Developing common quality indicators, a European guideline for perioperative pain management (e.g. for patients at high risk for experiencing severe pain and other outcome parameters) and common criteria for acute pain services might pave the way forward for improving acute pain management in Europe. Finally, the education of general and specialist staff should be aligned in Europe, for example, by using the curricula of the European Pain Federation (EFIC).

3. Pain originating from the lumbar facet joints.

INTRODUCTION: Pain originating from the lumbar facets can be defined as pain that arises from the innervated structures comprising the joint: the subchondral bone, synovium, synovial folds, and joint capsule. Reported prevalence rates range from 4.8% to over 50% among patients with mechanical low back pain, with diagnosis heavily dependent on the criteria employed. In well-designed studies, the prevalence is generally between 10% and 20%, increasing with age. METHODS: The literature on the diagnosis and treatment of lumbar facet joint pain was retrieved and summarized. RESULTS: There are no pathognomic signs or symptoms of pain originating from the lumbar facet joints. The most common reported symptom is uni- or bilateral (in more advanced cases) axial low back pain, which often radiates into the upper legs in a non-dermatomal distribution. Most patients report an aching type of pain exacerbated by activity, sometimes with morning stiffness. The diagnostic value of abnormal radiologic findings is poor owing to the low specificity. SPECT can accurately identify joint inflammation and has a predictive value for diagnostic lumbar facet injections. After "red flags" are ruled out, conservatives should be considered. In those unresponsive to conservative therapy with symptoms and physical examination suggesting lumbar facet joint pain, a diagnostic/prognostic medial branch block can be performed which remains the most reliable way to select patients for radiofrequency ablation. CONCLUSIONS: Well-selected individuals with chronic low back originating from the facet joints may benefit from lumbar medial branch radiofrequency ablation.

Mindfulness-based cognitive therapy for chronic noncancer pain and prescription opioid use disorder: A qualitative pilot study of its feasibility and the perceived process of change.

BACKGROUND: Mindfulness-based interventions have a positive impact on pain, craving, and well-being in both patients with chronic pain and those with opioid use disorder (OUD). Although data are limited, mindfulness-based cognitive therapy (MBCT) might be a promising treatment for patients with chronic noncancer pain combined with OUD. The aim of this qualitative study was to explore the feasibility and process of change during MBCT in this particular population. METHODS: In this qualitative pilot study, 21 patients who were hospitalized for rotation to buprenorphine/naloxone as agonist treatment for chronic pain and OUD were offered MBCT. Semistructured interviews were conducted to explore experienced barriers and facilitators to MBCT. Patients who participated in MBCT were also interviewed on their perceived process of change. RESULTS: Of 21 patients invited to participate in MBCT, 12 initially expressed interest but only four eventually participated in MBCT. The timing of the intervention, group format, somatic complaints, and practical difficulties were identified as the main barriers to participation. Facilitating factors included having a positive attribution toward MBCT, an intrinsic motivation to change, and practical support. The four MBCT participants mentioned several important mechanisms of change, including reduction of opioid craving and improved coping with pain. CONCLUSIONS: MBCT offered in the current study was not feasible for the majority of patients with pain and OUD. Changing the timing of MBCT by providing it at an earlier stage of the treatment and offering MBCT in an online format may facilitate participation.

Pain predict genetics: protocol for a prospective observational study of clinical and genetic factors to predict the development of postoperative pain.

INTRODUCTION: Postoperative pain remains a challenging medical condition impacting the quality of life of every patient. Although several predictive factors for postoperative pain have been identified, an adequate prediction of postoperative pain in patients at risk has not been achieved yet.The primary objective of this study is to identify specific genetic risk factors for the development of acute and chronic postoperative pain to construct a prediction model facilitating a more personalised postoperative pain management for each individual. The secondary objectives are to build a databank enabling researchers to identify other risk factors for postoperative pain, for instance, demographic and clinical outcome indicators; provide insight into (genetic) factors that predict pharmacological pain relief; investigate the relationship between acute and chronic postoperative pain. METHODS AND ANALYSIS: In this prospective, observational study, patients who undergo elective surgery will be recruited to a sample size of approximately 10 000 patients. Postoperative acute and chronic pain outcomes will be collected through questionnaires at different time points after surgery in the follow-up of 6 months. Potential genetic, demographic and clinical risk factors for prediction model construction will be collected through blood, questionnaires and electronic health records, respectively.Genetic factors associated with acute and/or chronic postoperative pain will be identified using a genome-wide association analysis. Clinical risk factors as stated in the secondary objectives will be assessed by multivariable regression. A clinical easy-to-use prediction model will be created for postoperative pain to allow clinical use for the stratification of patients. ETHICS AND DISSEMINATION: The Institutional Review Board of the Radboud university medical centre approved the study (authorisation number: 2012/117). The results of this study will be made available through peer-reviewed scientific journals and presentations at relevant conferences, which will finally contribute to personalised postoperative pain management. TRIAL REGISTRATION NUMBER: NCT02383342.

Buprenorphine/naloxone versus methadone opioid rotation in patients with prescription opioid use disorder and chronic pain: study protocol for a randomized controlled trial.

BACKGROUND: Opioids are effective in pain-management, but long-term opioid users can develop prescription opioid use disorder (OUD). One treatment strategy in patients with OUD is rotating from a short-acting opioid to a long-acting opioid (buprenorphine/naloxone (BuNa) or methadone). Both BuNa and methadone have been shown to be effective strategies in patients with OUD reducing opioid misuse, however data on head-to-head comparison in patients with chronic non-malignant pain and prescription OUD are limited. METHODS: This two-armed open-label, randomized controlled trial aims to compare effectiveness between BuNa and methadone in patients with chronic non-malignant with prescription OUD (n = 100). Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen. The primary outcome is opioid misuse 2 months after rotation. Secondary outcomes include treatment compliance, side effects, analgesia, opioid craving, quality of life, mood symptoms, cognitive and physical functioning over 2- and 6 months follow-up. Linear mixed model analysis will be used to evaluate change in outcome parameters over time between the treatment arms. DISCUSSION: This is one of the first studies comparing buprenorphine/naloxone and methadone for treating prescription OUD in a broad patient group with chronic non-malignant pain. Results may guide future treatment for patients with chronic pain and prescription OUD. Trial registration https://www.trialregister.nl/ , NL9781.

[Tapering of opioid use in primary care]. / Opioïden afbouwen in de eerstelijnszorg.

Although opioids are frequently used as treatment for chronic non-cancer related pain, the long term benefits on pain intensity and physical functioning are rather limited. Prolonged use of opioids is accompanied by multiple risks and side effects. It is important to regularly evaluate the effectiveness and the possibility of tapering of an opioid therapy. Tapering opioid use may improve physical function. Structured counselling by a healthcare professional facilitates successful tapering. In most cases, it will be possible to taper opioids in a primary care setting. If the treating physician feels incompetent to manage the tapering process, referral to specialized psychiatric care or a pain specialist can be considered. We propose a tapering rate between 10-35% of the previous dose per week in the primary care setting. Both pharmacological and non-pharmacological interventions can be used to ease the tapering.

Prevalence and Risk Factors for Acute Postoperative Pain After Elective Orthopedic and General Surgery at a Tertiary Referral Hospital in Tanzania.

BACKGROUND: In Africa, postoperative pain management is still a major problem with a prevalence of postoperative pain in up to 95.2% of the patients. There are little data on the prevalence and potential risk factors for postoperative pain in Tanzania. Therefore, we aimed to investigate these at Kilimanjaro Christian Medical Centre in Northern Tanzania. Our goal is to optimize pain management. METHODS: A prospective cohort study was carried out from December 2016 to April 2017. Patients ≥18 years admitted for elective general or orthopedic surgery were included in the study. Demographic data were collected during a pre-operative visit, and pain was assessed with a numerical rating scale (NRS 0-10) at 4, 24, 36 and 48 hours postoperatively. A NRS >3 was considered as moderate to severe postoperative pain. Potential risk factors for postoperative pain were identified using univariate and multivariable binary logistic regression analyses. RESULTS: A total of 281 patients were included in the study. The prevalence of postoperative pain was 61%, 73%, 67% and 58% at 4, 24, 36 and 48 hours after surgery, respectively. Pethidine was the most frequently prescribed analgesic for postoperative pain management (85.1%) in the first 24 hours postoperatively; only 1% received paracetamol or diclofenac, and 13% received tramadol. In the multivariable model, general anesthesia and intra-operative analgesia (OR = 3.70, 95% CI 1.70-8.04) were significant risk factors for postoperative pain. CONCLUSION: Pain is still inadequately managed at Kilimanjaro Christian Medical Centre leading to a high prevalence (73% on the first day after surgery) of reported postoperative pain in this study. It reflects the need for adequate postoperative analgesia, especially in low- and middle-income countries. Further research identifying risk factors in larger cohorts can be performed if adequate analgesia is given.

Acute Cytokine Response During Breast Cancer Surgery: Potential Role of Dexamethasone and Lidocaine and Relationship with Postoperative Pain and Complications - Analysis of Three Pooled Pilot Randomized Controlled Trials.

PURPOSE: An imbalance in perioperative cytokine response may cause acute pain and postoperative complications. Anesthetic drugs modulate this cytokine response, but their role in non-major breast cancer surgery is unclear. In an exploratory study, we investigated whether intravenous lidocaine and dexamethasone could modulate the cytokine response into an anti-inflammatory direction. We also evaluated interrelationships between cytokine levels, pain scores and postoperative complications. Our goal is to develop multimodal analgesia regimens optimizing outcome after breast cancer surgery. PATIENTS AND METHODS: Forty-eight patients undergoing a lumpectomy were randomly assigned to placebo or lidocaine (1.5 mg⋅kg-1 followed by 2 mg⋅kg-1⋅hour-1) supplemented by dexamethasone zero, 4 or 8 mg, yielding six groups of eight patients. Interleukin (IL)-1ß, IL-1Ra, IL-6, IL-10 levels and pain scores were measured at baseline and four hours postoperatively. We assessed postoperative complications occurring within 30 days. We noted persistent pain and infections as potential immune-related complications (PIRC). We used multiple regression to disentangle the effects of the individual study drugs (given by their partial regression coefficients (b)). Odds ratios (OR) estimated the link between pain scores and complications. RESULTS: Dexamethasone 8 mg increased IL-10 (b=12.70 (95% CI=8.06-17.34), P<0.001). Dexamethasone 4 mg and 8 mg decreased the ratio IL-6/IL-10 (b=-2.60 (-3.93 to -1.26), P<0.001 and b=-3.59 (-5.04 to -2.13), P<0.001, respectively). We could not show modulatory effects of lidocaine on cytokines. High pain scores were linked to the occurrence of PIRC's (OR=2.028 (1.134-3.628), P=0.017). Cytokine levels were not related either to acute pain or PIRC. CONCLUSION: Dexamethasone modulated the perioperative cytokine response into an anti-inflammatory direction. An overall lidocaine effect was not found. Patients with higher pain scores suffered from more 30-day PIRCs. Cytokine levels were not associated with pain or more postoperative complications, even not with PIRC. Larger studies in breast cancer surgery are needed to confirm these explorative results.

A systematic summary and comparison of animal models for chemotherapy induced (peripheral) neuropathy (CIPN).

Despite the large amount of human and experimental studies no effective (prophylactic) treatment exists for chemotherapy induced peripheral neuropathy (CIPN), a disabling side effect of many cancer treatments. One of the underlying reasons for this could be that often the preclinical animal models used are not the best representation of the clinical situation. We therefore present a systematic summary and comparison of all animal models currently described in literature for CIPN focusing on stimulus evoked pain-like behaviour and neurophysiological alterations in nerve function (650 included papers, and a comparison of 183 models), that resulted in a clear overview of the most effective and robust CIPN models using an administration route used in clinical practice. Using our three-step approach (step 1: efficacy; step; 2 robustness and step 3: mimicking the clinical situation) we show that all mice CIPN models treated with either paclitaxel or cisplatin using an administration route used in clinical practice seem suitable models. Three specific models using paclitaxel or cisplatin that stand out are 1) C57BL/6 female mice receiving paclitaxel and 2) CD1 male mice receiving paclitaxel and 3) C57BL/6 male mice receiving cisplatin. This overview may help scientists selecting suitable CIPN models for their research. We hypothesize that by using effective and robust animal models that mimic the clinical situation as much as possible, the translational value of preclinical study results with respect to the potential of identifying promising treatments for CIPN in the future, will prove. The methodology described in this paper, aimed at comparing animal models, is novel and can be used by scientist in other research fields as well.

Pulsed radiofrequency or anterior neurectomy for anterior cutaneous nerve entrapment syndrome (ACNES) (the PULSE trial): study protocol of a randomized controlled trial.

BACKGROUND: Some patients with chronic abdominal pain suffer from an anterior cutaneous nerve entrapment syndrome (ACNES). This somewhat illusive syndrome is thought to be caused by the entrapment of end branches of the intercostal nerves residing in the abdominal wall. If ACNES is suspected, a local injection of an anesthetic agent may offer relief. If pain is recurrent following multiple-injection therapy, an anterior neurectomy entailing removal of the entrapped nerve endings may be considered. After 1 year, a 70% success rate has been reported. Research on minimally invasive alternative treatments is scarce. Pulsed radiofrequency (PRF) treatment is a relatively new treatment for chronic pain syndromes. An electromagnetic field is applied around the nerve in the hope of leading to pain relief. This randomized controlled trial compares the effect of PRF treatment and neurectomy in patients with ACNES. METHODS: Adult ACNES patients having short-lived success following injections are randomized to PRF or neurectomy. At the 8-week follow-up visit, unsuccessful PRF patients are allowed to cross over to a neurectomy. Primary outcome is pain relief after either therapy. Secondary outcomes include patient satisfaction, quality of life, use of analgesics and unanticipated adverse events. The study is terminated 6 months after receiving the final procedure. DISCUSSION: Since academic literature on minimally invasive techniques is lacking, well-designed trials are needed to optimize results of treatment for ACNES. This is the first large, randomized controlled, proof-of-concept trial comparing two therapy techniques in ACNES patients. The first patient was included in October 2015. The expected trial deadline is December 2017. If effective, PRF may be incorporated into the ACNES treatment algorithm, thus minimizing the number of patients requiring surgery. TRIAL REGISTRATION: Nederlands Trial Register (Dutch Trial Register), NTR5131 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5131 ). Registered on 15 April 2015.

Intravenous Lidocaine: Old-School Drug, New Purpose-Reduction of Intractable Pain in Patients with Chemotherapy Induced Peripheral Neuropathy.

Background. Treatment of intractable pain due to chemotherapy induced peripheral neuropathy (CIPN) is a challenge. Intravenous (iv) lidocaine has shown to be a treatment option for neuropathic pain of different etiologies. Methods. Lidocaine (1.5 mg/kg in 10 minutes followed by 1.5 mg/kg/h over 5 hours) was administered in nine patients with CIPN, and analgesic effect was evaluated during infusion and after discharge. The immediate effect of lidocaine on pressure pain thresholds (PPT) and the extent of the stocking and glove distribution of sensory abnormalities (cold and pinprick) were assessed. Results. Lidocaine had a significant direct analgesic effect in 8 out of 9 patients (P = 0.01) with a pain intensity difference of >30%. Pain reduction persisted in 5 patients for an average of 23 days. Lidocaine did not influence mean PPT, but there was a tendency that the extent of sensory abnormalities decreased after lidocaine. Conclusion. Iv lidocaine has direct analgesic effect in CIPN with a moderate long-term effect and seems to influence the area of cold and pinprick perception. Additional research is needed, using a control group and larger sample sizes to confirm these results.