A systematic review of qualitative research exploring patient and health professional perspectives of breakthrough cancer pain.

PURPOSE: Breakthrough cancer pain (BtCP) is a prevalent health issue which is difficult to manage. A plethora of quantitative research in this area exists. There is a paucity of research on the perspectives of health professionals and patients surrounding domains impacting effective treatment, including definitions of BtCP, treatment, and education opportunities. This review aims to identify and synthesize the extent of qualitative research exploring health professional and patient perspectives of BtCP. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach was undertaken. The approach was registered with Prospero. MEDLINE, EMBASE, and Web of Science were searched for peer-reviewed literature published any date prior to May 19, 2022. Eligible sources must have considered health professional and/or patient perspectives of BtCP. A narrative synthesis approach was utilized. RESULTS: Three sources met the review criteria. One source explored nurse perspectives, while two sources explored patient perspectives. Study quality was moderate to high. Overlapping themes across the three studies included communication, defining BtCP, impact of BtCP, management of BtCP, perceptions of BtCP, analgesia and pain relief, and training and professional development. CONCLUSION: Given limited research investigating clinician and patient perspectives of BtCP, a rich understanding informed by exploratory qualitative methods around identification, best management strategies, professional development, and factors promoting and inhibiting best practice remains unclear. Further qualitative inquiry is warranted, and it is expected such research will inform BtCP clinical guidelines.

Knowledge and practice of the management of breakthrough cancer pain among general practitioners providing palliative care in Shanghai, China: a cross-sectional survey.

OBJECTIVE: This study examined knowledge and practice of breakthrough cancer pain (BTcP) management among general practitioners (GPs) providing palliative care in Shanghai. DESIGN: Cross-sectional study using a self-administered questionnaire. SETTING AND PARTICIPANTS: A total of 393 GPs providing palliative care in 32 community health service centres in Shanghai were recruited by stratified cluster random sampling between 1 May and 30 June 2022. OUTCOME MEASURES: Knowledge and practice concerning BTcP management. RESULTS: A total of 375 questionnaires were collected and declared valid. The median knowledge score was 11 out of 21 points. Only 36.3% (n=136) of the participating GPs scored 11 points or more, which was categorised as good knowledge. Only 24.8% (n=93) of the GPs used Davies' adapted diagnostic algorithm as the gold standard for diagnosis. All of the GPs assessed the intensity of BTcP; however, less than a quarter of the GPs evaluated the relationship between background pain and BTcP (22.1%, n=83), the impact of BTcP on activities of daily living (24.0%, n=90), the impact of BTcP on social relationships (14.4%, n=54) and the impact of BTcP on mood (10.1%, n=38). 56.5% (n=212) of the GPs reported that they used pain tools in the assessment of BTcP. All of the GPs prescribed immediate-release morphine as rescue medication for relieving BTcP; however, 60.5% (n=227) prescribed the dose based on their personal experiences, irrespective of the basal opioid dose, and 57.3% (n=215) did not conduct dose titration after providing the initial dose. No GPs reported that they ever administered interventional treatment to their patients. CONCLUSIONS: Insufficient knowledge and inappropriate behaviours in BTcP diagnosis, assessment and treatment were identified. There is an urgent need to improve BTcP management among GPs providing palliative care in Shanghai.

Intrathecal Analgesia via a Percutaneous Port With Patient-Controlled Intrathecal Analgesia for the Management of Movement-Evoked Breakthrough Cancer Pain of Refractory Lower Extremity Cancer Pain: A Retrospective Review.

BACKGROUND: Intrathecal analgesia (ITA) is a valuable treatment option for refractory cancer-related pain. However, there is still no general consensus on the analgesic effect of movement-evoked breakthrough pain (MEBTP) in the ITA setting. OBJECTIVES: This study aimed to conduct a retrospective observational study to examine the effect of ITA via percutaneous port (ITAPP) with patient-controlled ITA (PCIA) on analgesic efficacy, emphasizing MEBTP in patients with refractory lower extremity cancer pain. STUDY DESIGN: A retrospective chart review included all patients with refractory lower extremity cancer pain who received ITAPP at our hospital between January 2017 and December 2020. METHODS: Data on the Numeric Rating Scale scores of spontaneous resting pain intensity (SRPI) and MEBTP intensity (MEPI), opioid doses, and perceived time to onset were collected from medical records prior to ITAPP and at a one-month postimplant visit. RESULTS: A total of 16 patients were included in the study group. Mean SRPI decreased from 8.75 pre-ITAPP to 3.75 post-ITAPP (P < 0.05); mean MEPI fell from 8.83 pre-ITAPP to 4.25 post-ITAPP (P < 0.05); mean daily morphine equivalent dosing decreased from 360 mg/d to 48 mg/d (P < 0.05); and mean daily morphine equivalent dosing for MEBTP decreased from 87 mg/d to 6 mg/d (P < 0.05). Both total and breakthrough dosing of conventional opioid medications significantly decreased following the initiation of ITAPP with PCIA. The mean perceived time to onset with conventional MEBT medications was 38 minutes, and the mean perceived time to onset with PCIA was 8 minutes (P < 0.05). LIMITATIONS: An effective analysis of IT opioid efficacy was not possible because the power of such a small sample size was low. Second, it is a retrospective study without long-term follow-ups. CONCLUSIONS: In patients with refractory lower extremity cancer pain, ITAPP with PCIA was associated with improved pain control. Compared with conventional MEBTP regimens, appropriate ITAPP with PCIA provided superior analgesia and a much faster onset of action.

Efficacy of Patient-Controlled Intravenous Analgesia with Esketamine for Herpes Zoster Associated with Breakthrough Pain.

BACKGROUND: Some patients with herpes zoster (HZ) experience an intermittent spontaneous, short-lived and severe pain, which is called breakthrough pain (BTP). The effect of analgesic drugs and invasive procedures is not significant. Therefore, treatment of HZ associated with BTP is challenging. Esketamine is a new N-methyl-D-aspartate receptor antagonist, with enhanced analgesic effects. This study aimed to evaluate the efficacy and adverse reactions of patient-controlled intravenous analgesia (PCIA) with low-dose esketamine for HZ associated with BTP. OBJECTIVES: To evaluate the efficacy and adverse reactions of PCIA with low-dose esketamine for HZ associated with BTP. STUDY DESIGN: A retrospective, observational study. SETTING: The study was carried out in the Pain Department of the Affiliated Hospital of Jiaxing University in Jiaxing, China. METHODS: The clinical data of HZ associated with BTP treated by PCIA with low-dose esketamine at the Pain Department of the Affiliated Hospital of Jiaxing University, between October 2015 to October 2021, were collected retrospectively. The Numeric Rating Scale (NRS-11) scores of rest pain (RP) and BTP, frequency of BTP, Pittsburgh Sleep Quality Index (PSQI) score, and fasting blood glucose (FBG) were recorded and analyzed before treatment (T0) and on days one (T1) and 3 (T2), week one (T3), months one (T4), 3 (T5), and 6 (T6) after treatment. Adverse reactions during the treatment were recorded. RESULTS: Twenty-five patients treated by PCIA with low-dose esketamine were included finally. Compared with T0, the NRS-11 scores of RP at T2, T3, T4, T5, and T6 decreased significantly (P < 0.05). The NRS-11 score of RP at T4 was significantly lower than that of T3 (P < 0.001), but there was no statistical difference between T5 and T4 (P > 0.05), the efficacy of esketamine in the treatment of RP was stable at one month after treatment. Likewise, compared with T0, the NRS-11 scores of BTP, frequency of BTP, and PSQI score decreased significantly at each time point after treatment (P < 0.05). These at T5 were significantly lower than T4 (P < 0.05), but there was no statistical difference between T6 and T5 (P > 0.05), the efficacy of esketamine was stable at 3 months after treatment. FBG also decreased significantly at each time point after treatment (P < 0.05), it tended to be normal and stable one month after treatment. All patients had mild symptoms of dizziness during treatment, and though a slight increase in noninvasive blood pressure (BP) was noted in all, the elevated BP did not exceed 30% of the baseline value. Four patients (16%) developed nausea without vomiting. There were no serious adverse reactions, such as respiratory depression. LIMITATIONS: The nonrandomized, single-center, small sample size, retrospective design is a major limitation of this study. CONCLUSIONS: PCIA with low-dose esketamine has a significant and long-term effect in the treatment of HZ associated with BTP. The RP was controlled, and the degree and frequency of BTP were significantly reduced after treatment, leading to improved quality of life. There were no serious adverse reactions worthy of clinical promotion.

Breakthrough pain in patients with multiple myeloma: a secondary analysis of IOPS MS study.

OBJECTIVE: The aim of this study was to characterize breakthrough pain (BTcP) in patients with multiple myeloma (MM). PATIENTS AND METHODS: This was a secondary analysis of a large multicenter study of patients with BTcP. Background pain intensity and opioid doses were recorded. The BTcP characteristics, including the number of BTcP episodes, intensity, onset, duration, predictability, and interference with daily activities were recorded. Opioids prescribed for BTcP, time to achieve a meaningful pain relief after taking a medication, adverse effects, and patients' satisfaction were assessed. RESULTS: Fifty-four patients with MM were examined. In comparison with other tumors, in patients with MM BTcP was more predictable (p=0.04), with the predominant trigger being the physical activity (p<0.001). Other BTcP characteristics, pattern of opioids used for background pain and BTcP, satisfaction and adverse effects did not differ. CONCLUSIONS: Patients with MM have their own peculiarities. Given the peculiar involvement of the skeleton, BTcP was highly predictable and triggered by movement.

Breakthrough cancer pain in the radiotherapy setting: a systematic and critical review.

INTRODUCTION: Breakthrough pain (BP) is a complex phenomenon that has been reported to have a relevant role in the global management of cancer pain. Radiotherapy (RT) has a fundamental part in the treatment of many pain conditions, particularly oral mucositis and painful bone metastases. AREAS COVERED: The literature regarding the phenomenon of BP in the radiotherapy setting was reviewed. Three areas were assessed, including epidemiology, pharmacokinetics, and clinical data. EXPERT OPINION: Qualitative and quantitative data regarding BP in the RT setting are poor in terms of scientific evidence. Most papers assessed fentanyl products, particularly fentanyl pectin nasal spray, to resolve possible problems with transmucosal absorption of fentanyl due to mucositis of the oral cavity in patients with head and neck cancer or to prevent and treat procedural pain during RT sessions. According to the lack of clinical studies with large number of patients, BP should be included in the agenda of radiation oncologists.

Predicting tolerability of high-dose fentanyl buccal tablets in cancer patients.

BACKGROUND & AIMS: Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for breakthrough cancer pain (BTcP) and FBT titration is needed to optimize BTcP management. We aimed to predict which patients could tolerate a high dose of FBT (400 µg or more at a time). METHODS: A retrospective analysis was performed to assess the final FBT dose. The final FBT doses were compared according to the clinical features. The prediction accuracy of patients tolerant of 400 µg or higher FBT was compared using the area under the receiver operating characteristic (ROC) curves. A risk scoring model based on the odds ratio (OR) was developed from the final multivariable model, and patients were assigned into two groups: low tolerance (0-1 point) and high tolerance (2-3 points). RESULTS: Among 131 patients, the most frequently effective dose of FBT was 200 µg (54%), followed by 100 µg (30%). The median value of morphine equivalent daily doses (MEDD) was 60 mg/day, and the most common daily use was 3-4 times/day. In multivariable analysis, male sex, younger age, and use of FBTs three or more times per day were independently associated with high-dose FBT. According to the risk scoring model, the patients with a final FBT of 400 µg or higher were significantly more in the high tolerance group (17%) compared to the low tolerance group (3%; p = 0.023). CONCLUSIONS: According to the dose relationship between the final FBT dose and the clinical features, three factors (sex, age, daily use of FBT) were independently associated with the final dose of FBT. Our risk score model could help predict tolerance to high-dose FBT and guide the titration plan for BTcP.

Successful buprenorphine transition while overlapping with a full opioid agonist to treat chronic pain: a case report.

Buprenorphine is a partial mu opioid agonist that has been increasingly utilized to treat patients with chronic pain and opioid use disorder (OUD). The drug has proven to provide significant chronic pain relief at low doses ranging from 75 to 1800 mcg. The conventional buprenorphine transitional process delays its introduction until patients begin withdrawal. However, this process can pose a barrier to both patients and providers due to some patients' inability to tolerate traditional prerequisite withdrawal. To our knowledge, this is a rare reported case to describe a transitional process utilizing buccal buprenorphine in which a patient with chronic pain simultaneously tapered completely off an extended-release (ER) full opioid agonist and uptitrated buprenorphine. The patient was weaned from oxycodone ER 30 mg every 12 h and oxycodone/acetaminophen 10/325 mg 3x/day for breakthrough pain utilizing an unconventional approach. Tapering down to oxycodone ER 20 mg 2x/day for the first 2 weeks was successful. However, reducing to oxycodone ER 10 mg 2x/day for the following 2 weeks presented adherence difficulty and increased breakthrough pain. At this time, buccal buprenorphine was added at 300 mcg daily for 3 days. From days 4 to 6, buprenorphine was increased to 300 mcg 2x/day and oxycodone ER decreased to 10 mg daily. Six days later, oxycodone ER was discontinued and oxycodone/acetaminophen continued as needed. The patient exhibited no signs of withdrawal and adequate relief of symptoms through this tapering process. At the 1-month follow-up, the patient was doing well and was being treated solely with buprenorphine and oxycodone/acetaminophen to control her breakthrough pain. After 5 months, buprenorphine was increased to 600 mcg 2x/day and her oxycodone/acetaminophen decreased to 5/325 mg 3x/day as needed. From the start of the patient's taper to her current transition, the patient reduced her morphine milligram equivalent (MME) dosage from 135 MME to 22.5 MME. The Clinical Opioid Withdrawal Scale (COWS), which measures the severity of a patient's opioid withdrawal symptoms, was consistently less than 5. This buprenorphine schedule demonstrated a successful tapering approach for this patient because she had reported improved quality of life and function. A patient-centered osteopathic treatment approach was utilized when the patient presented with mid-taper adherence difficulty. Transitioning patients from full to partial opioid agonists could become an important practice standard for patient safety not only for formal pain management practices but also in primary care, family practice, and even geriatric offices.

Increased quality of life in patients with breakthrough cancer pain after individualized therapy: the CAVIDIOM study.

Aim: To evaluate the quality of life (QoL) in patients with breakthrough cancer pain (BTcP) in Spanish medical oncology departments. Patients & methods: In a prospective, observational, multicenter study, we assessed QoL using the EQ-5D-5L instrument at baseline and after 15 and 30 days of individualized BTcP therapy, as well as BTcP characteristics and treatment. Results: Patients (n = 118) were mainly women, over 64 years old and with advanced cancer. QoL improved at 15 (p = 0.013) and 30 days (p = 0.011) versus baseline. Individualized BTcP therapy consisted mostly of rapid-onset opioids (transmucosal fentanyl at doses of 67-800 µg) according to the physician evaluation. BTcP improved, including statistically significant reductions in intensity, duration, number of episodes in the last 24 h and time to onset of BTcP relief. Conclusion: QoL increased after individualized pain therapy in patients with advanced cancer and BTcP in medical oncology departments.

Cancer patients can experience flares of pain, called breakthrough pain (BTcP), despite treatment with painkillers. Although BTcP can be excruciating, its intensity and other characteristics depend on several factors, including its treatment. However, even if treated, BTcP can impair quality of life for cancer patients. We assessed quality of life in 118 patients with advanced cancer and BTcP treated in 13 medical oncology departments across Spain. We treated BTcP with individualized therapy, taking into account both pain-related and patient-related factors. We also measured quality of life using a specific, widely-used questionnaire at the study visits: at onset of individualized pain therapy and after 3, 15 and 30 days' treatment. At each visit, flare-up pain therapy was adjusted or maintained as necessary. Throughout the study, quality of life and sleep quality improved for all participants. Furthermore, there was a greater reduction in intensity, duration and frequency of BTcP. The most common treatments for flare-ups were low doses of rapid-onset opioids (fentanyl given by sublingual, buccal or nasal administration), which were much better tolerated than high-dose opioids. Overall, the study showed that quality of life in patients with advanced cancer and BTcP increased after individualized pain therapy, mainly with low doses of rapid-onset opioids.

Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial.

BACKGROUND: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. METHODS: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. RESULTS: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (P<.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 (P=.024) among the 3 arms. No severe adverse event occurred in any arm. CONCLUSIONS: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.

Breakthrough Cancer Pain: What Outpatient Oncology Nurses Need to Know.

Breakthrough cancer pain (BCP) is a devastating symptom that can occur in individuals with cancer throughout the disease trajectory, particularly in those with advanced cancer. Oncology nurses have a critical role in treating.

Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain.

Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial.

Importance: The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain. Objective: To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery. Design, Setting, and Participants: This parallel, 2-group, assessor-blind, pragmatic pilot RCT was conducted from January 29 to September 3, 2020 (last follow-up on October 2, 2020). at 2 university-affiliated hospitals in Montreal, Quebec, Canada. Participants were adult patients (aged ≥18 years) undergoing outpatient abdominal (ie, cholecystectomy, appendectomy, or hernia repair) or breast (ie, partial or total mastectomy) general surgical procedures. Exclusion criteria were contraindications to drugs used in the trial, preoperative opioid use, conditions that could affect assessment of outcomes, and intraoperative or early complications requiring hospitalization. Interventions: Patients were randomized 1:1 to receive OA (around-the-clock nonopioids and opioids for breakthrough pain) or OFA (around-the-clock nonopioids with increasing doses and/or addition of nonopioid medications for breakthrough pain) after postoperative discharge. Main Outcomes and Measures: Main outcomes were a priori RCT feasibility criteria (ie, rates of surgeon agreement, patient eligibility, patient consent, treatment adherence, loss to follow-up, and missing follow-up data). Secondary outcomes included pain intensity and interference, analgesic intake, 30-day unplanned health care use, and adverse events. Between-group comparison of outcomes followed the intention-to-treat principle. Results: A total of 15 surgeons were approached; all (100%; 95% CI, 78%-100%) agreed to have patients recruited and adhered to the study procedures. Rates of patient eligibility and consent were 73% (95% CI, 66%-78%) and 57% (95% CI, 49%-65%), respectively. Seventy-six patients were randomized (39 [51%] to OA and 37 [49%] to OFA) and included in the intention-to-treat analysis (mean [SD] age, 55.5 [14.5] years; 50 [66%] female); 40 (53%) underwent abdominal surgery, and 36 (47%) underwent breast surgery. Seventy-five patients (99%; 95% CI, 93%-100%) adhered to the allocated treatment; 1 patient randomly assigned to OFA received an opioid prescription. Seventeen patients (44%) randomly assigned to OA consumed opioids after discharge. Seventy-three patients (96%; 95% CI, 89%-99%) completed the 30-day follow-up. The rate of missing questionnaires was 37 of 3724 (1%; 95% CI, 0.7%-1.4%). All the a priori RCT feasibility criteria were fulfilled. Conclusions and Relevance: The findings of this pilot RCT support the feasibility of conducting a robust, full-scale RCT to inform evidence-based prescribing of analgesia after outpatient general surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04254679.

The incidence of breakthrough pain associated with programmed intermittent bolus volumes for labor epidural analgesia: a randomized controlled trial.

BACKGROUND: In this randomized, blinded study, we evaluated the effects of different programmed intermittent epidural bolus (PIEB) volumes for labor analgesia on the incidence of breakthrough pain and other analgesic outcomes. METHODS: Nulliparous women with term cephalic singleton pregnancies who requested labor analgesia had epidural analgesia initiated with 10 mL 0.1% ropivacaine with sufentanil 0.3 µg/mL. The pump was programmed to deliver a 4, 6 or 8 mL bolus every 45 min (groups 4, 6 or 8, respectively). The primary outcome was the incidence of breakthrough pain, defined as inadequate analgesia after two patient-controlled epidural analgesia administrations in a 20-min period. Secondary outcomes included ropivacaine consumption, time of the first patient-controlled epidural analgesia request, duration of the second stage of labor, and incidence of motor block. RESULTS: Among 210 women randomly allocated the incidence of breakthrough pain was 34.9%, 19.7%, and 13.1%, for groups 4, 6 and 8, respectively (P=0.011). The incidence of breakthrough pain in group 8 was lower than in group 4 (P=0.006). The median (interquartile range) hourly ropivacaine consumption was 8.2 mg/h (7.1-11.3), 10.4 mg/h (9.2-13.0), and 12.0 mg/h (11.2-13.8) in groups 4, 6 and 8, respectively (P <0.001). Group 8 had a longer duration of effective analgesia and longer second stage of labor than group 4. There was no significant difference between groups in the incidence of motor block. CONCLUSION: The larger PIEB volumes were preferred for epidural labor analgesia compared with a smaller volume because of improved analgesia without clinically significant increases in adverse effects.

Retrospective Observational Study on the Characteristics of Pain and Associated Factors of Breakthrough Pain in Advanced Cancer Patients.

Objective: This study aimed to conduct a retrospective observational study to understand the status of characteristics of pain and identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP) in advanced cancer patients. Methods: Advanced cancer patients over 18 years of age; diagnosed with cancer of any type and stage III or IV in the palliative care ward with available data were enrolled between 2018 and 2020. Demographic data and pain-related information were collected by using structured electronic extraction form from Hospital Information System (HIS). Patients who had well-controlled background pain with an intensity ≤4 on a 0-10 numerical scale for >12 hours/day, the presence of transient exacerbations of pain with moderate-severe intensity (≧5), and clearly distinguish from background pain were regarded to have suffered BTP. Spearman correlation was conducted to explore the relationship between pain score and demographics characteristics. Factors significant in univariate analysis were included in the multiple regression model to explore independent predictive factors associated with the BTP. Results: Of 798 advanced cancer patients, the mean age was 56.7 (SD = 11.84) years. Lung cancer (29.95%) was the most common cancer, and pain (93%) was the most common symptom. More than half (n = 428, 53.6%) of the patients experienced BTP. The median number of BTP episodes was 4 (IQR = 2, 7, range: 1-42). The median intensity of BTP was 6 (IQR = 6, 7, range 5-10). Patients with severe background pain or BTP had longer hospital stay and more symptoms. Besides, more severe background pain was related to higher activity of daily living. Intramuscular injection of hydromorphone hydrochloride was the main medication for BTP onset. Younger age, background pain, anorexia, and constipation were independently associated with the presentation of BTP. BTP pain intensity was independently associated with bloating. Symptom numbers were an independent factor and positively associated with BTP episodes. Conclusions: BTP resulted in poor prognosis, which has a variable presentation depending on interdependent relationships among different characteristics. Good controlling of background pain and assessment of pain-related symptoms are essential for BTP management. BTP should be managed individually, especially the invisible pain among aged patients. Furthermore, BTP-related education and training were still needed.

Acute postoperative pain management protocols in podiatric surgery within Australia: a Delphi study.

BACKGROUND: There is limited evidence in the literature to describe an analgesic protocol that takes into consideration the extent of foot and ankle surgery. The aim of this study was to develop a guide for acute postoperative pain management for podiatric surgery in Australia, and to identify opportunities to improve the current list of scheduled medicines available to podiatric surgeons. METHODS: A Delphi method involving 3 survey rounds was employed for this study. Twelve expert panellists in the field of podiatric surgery and anaesthesiology were invited to participate, and 10 panellists remained by the end of the study. Round 1 involved 15 open-ended questions. These answers formed the basis of the 55 statements that were developed for the following 2 survey rounds, where panellists rated the appropriateness of each statement on a 9-point Likert scale. The third survey round was an opportunity for panellists to revise their answers to each statement in light of the majority response. RESULTS: For mild acute postoperative pain, non-opioid oral analgesics were recommended as an appropriate management option. For moderate and severe acute postoperative pain, both non-opioid and opioid products were found to be appropriate by the majority. It was agreed that oral opioids be reserved for breakthrough pain at all severity levels. All other statements in the Delphi study pertaining to drug hypersensitivities or allergies, stratification of pain management, opioid prescription concerns, and access to pain medications were accepted as appropriate by the majority of panellists. CONCLUSION: The agreed approach to acute postoperative pain management for podiatric surgeons in Australia was with a stepwise approach, utilising multimodal therapy, and reserving oral opioids for breakthrough pain. Additionally, there was consensus for podiatric surgeons in Australia to have wider access to alternative analgesics and anti-emetics that have similar or improved efficacies with better safety profiles.

Clinical Practice Guidelines in the Management of Breakthrough Cancer Pain: A Systematic Review using the Appraisal of Guidelines for Research and Evaluation (AGREE II) Instrument.

BACKGROUND: Several clinical practice guidelines (CPGs), consensus statements, and recommendations currently exist for the diagnosis and management of breakthrough cancer pain (BTcP). These documents have considerable variability amongst them, and to date, their quality and methodologic rigor have not been appraised. AIM: We aim to identify and perform a quality appraisal of CPGs for the diagnosis and management of BTcP using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. METHODS: A comprehensive literature search was performed in MEDLINE (via PubMed), EMBASE, and SCOPUS databases up until January 1, 2021. Four reviewers independently evaluated each guideline using the AGREE II instrument. Scaled domain scores were generated and the threshold used for satisfactory quality was >60%. Additionally, intraclass correlation coefficients (ICC) were calculated to determine level of agreement between reviewers. RESULTS: Eleven guidelines were selected for final evaluation based on inclusion/exclusion criteria. Only one guideline was classified of "average" quality while the rest were classified as "low" quality. The "Editorial Independence" (70.46 ± 35.7) and "Scope and Purpose" (64.78 ± 12.5) domains received the highest mean scores, while the "Applicability" (32.58 ± 13.5) and "Rigor of Development" (35.04 ± 9.0) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.790-0.988). CONCLUSIONS: Reflecting upon our quality appraisal, it is evident that the quality and methodologic rigor of BTcP guidelines can be improved upon in the future. Our findings also elucidate the existing variability/discrepancies among guidelines in diagnostic criteria and management of BTcP.

Low-dose sublingual fentanyl improves quality of life in patients with breakthrough cancer pain in palliative care.

Aim: This subanalysis of the CAVIDIOPAL study evaluated the impact of individualized management of breakthrough cancer pain (BTcP) with fentanyl on the quality of life (QoL) of advanced cancer patients in Spanish palliative care units. Patients & methods: This was a prospective, observational, multicenter study. The European Organization for Research and Treatment of Cancer's QLQ-C30 questionnaire was used at baseline (V0) and visit 28 (V28). Results: Ninety-five patients were mainly treated with 67-133 µg fentanyl, showing a notable reduction in intensity (visual analog scale: 8.0 [V0] to 4.6 [V28]), frequency and duration of BTcP episodes shortly after the first 1-2 weeks of treatment, with significantly improved QoL (global health status: 31.1 [V0] to 53.1 [V28]). Conclusion: Low-dose sublingual fentanyl effectively reduced BTcP in advanced cancer patients in palliative care units, significantly improving QoL. Clinical trial registration: NCT02840500 (ClinicalTrials.gov).

After the CAVIDIOPAL study, we carried out an additional analysis to evaluate the impact of individualized management of breakthrough cancer pain, using the analgesic drug fentanyl, on quality of life (QoL) of advanced cancer patients receiving palliative care in Spain. We performed a prospective, observational, multicenter study, in which patients' QoL was assessed using a validated questionnaire at baseline (day 0) and after 28 days of fentanyl treatment. Of the 95 patients included in the study, the majority were treated with low doses of fentanyl and showed significant pain relief. The intensity, frequency and duration of breakthrough cancer pain episodes were notably reduced shortly after the first 1­2 weeks of treatment. Moreover, patients' QoL significantly improved during fentanyl treatment from baseline to day 28. A global impression of improvement was reported by both patients and clinicians.

Bibliometric Network Analysis on Rapid-Onset Opioids for Breakthrough Cancer Pain Treatment.

BACKGROUND AND OBJECTIVES: Proper breakthrough cancer pain (BTcP) management is of pivotal importance. Although rapid-acting, oral and nasal transmucosal, fentanyl formulations (rapid-onset opioids, ROOs) are licensed for BTcP treatment, not all guidelines recommend their use. Presumably, some research gaps need to be bridged to produce solid evidence. We present a bibliometric network analysis on ROOs for BTcP treatment. METHODS: Documents were retrieved from the Web of Science (WOS) online database. The string was "rapid onset opioids" or "transmucosal fentanyl" and "breakthrough cancer pain". Year of publication, journal metrics (impact factor and quartile), title, document type, topic, and clinical setting (in-patients, outpatients, and palliative care) were extracted. The software tool VOSviewer (version 1.6.17) was used to analyze the semantic network analyzes, bibliographic coupling, journals analysis, and research networks. RESULTS: 502 articles were found in WOS. A declining trend in published articles from 2014 to 2021 was observed. Approximately 50% of documents regard top quartile (Q1) journals. Most articles focused on ROOs efficacy, but abuse and misuse issues are poorly addressed. With respect to article type, we calculated 132 clinical investigations. The semantic network analysis found interconnections between the terms "breakthrough cancer pain," "opioids," and "cancers." The top co-cited article was published in 2000 and addressed pain assessment. The largest number of partnerships regarded the United States, Italy, and England. CONCLUSION: In this research area, most articles are published in top-ranked journals. Nevertheless, paramount topics should be better addressed, and the implementation of research networks is needed.

Analyzing Differences in Perception between Oncologists and Patients to Adapt Pharmacological Treatment for Breakthrough Cancer Pain: Observational ADAPTATE Study.

Background: Transmucosal fentanyl (TF), used for breakthrough cancer pain (BTcP) treatment, has different formulations with distinctive attributes. The hypothesis is that, in shared decision making for the prevention of certain therapeutic problems, doctors and patients assign different value to the characteristics of treatment options. Aim: The aim of this study was to assess the discordance between the oncologists' opinion of attributes of TF and patients' expectations in BTcP treatment. Methods: This is a multicenter, cross-sectional observational study using simultaneous written surveys of doctors and patients suffering from BTcP episodes. The opinion of Spanish oncologists and patients regarding the importance of 14 different attributes of TF treatment (start of action, potency, duration, presentations and doses available, ease of use, titration, administration time, need for saliva, oral mucositis, rhinitis, adverse events, risk of abuse, evidence available, and need for instructions or health personnel to handle the medication), using two surveys, one for each group. Results: Sixty-three clinical oncologists and 272 patients participated in the study. The patients' satisfaction with and knowledge of BTcP treatment was 6.4 and 6.8 points, respectively (scale 1-9). The attributes with the highest relevance were shared by both groups, although their priority differed. Significant differences were observed in the greater importance given by oncologists (onset and duration of analgesia, need for saliva, presence of mucositis, and time required for patient education) and patients (risk of opioid abuse/aberrant behavior). Conclusion: Our results confirm that some aspects that most concern patients about the treatment of BTcP differ from those to which oncologists attach most importance. Increased patient awareness and education about BTcP and its treatment could lead to greater satisfaction and better patient involvement in therapeutic decisions. Certain barriers need to be overcome, such as lack of time in consultations and poor communication skills of oncologists that hinder patient health education.