Neuropathic pain after surgery - A clinical validation study and assessment of accuracy measures of the 5-item NeuPPS scale.

OBJECTIVE: The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. METHODS: Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. RESULTS: Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. CONCLUSION: The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

Quantitative somatosensory assessments in patients with persistent pain following groin hernia repair: A systematic review with a meta-analytical approach.

OBJECTIVES: Quantitative sensory testing (QST) provides an assessment of cutaneous and deep tissue sensitivity and pain perception under normal and pathological settings. Approximately 2-4% of individuals undergoing groin hernia repair (GHR) develop severe persistent postsurgical pain (PPSP). The aims of this systematic review of PPSP-patients were (1) to retrieve and methodologically characterize the available QST literature and (2) to explore the role of QST in understanding mechanisms underlying PPSP following GHR. METHODS: A systematic literature search was conducted from JAN-1992 to SEP-2022 in PubMed, EMBASE, and Google Scholar. For inclusion, studies had to report at least one QST-modality in patients with PPSP. Risk of bias assessment of the studies was conducted utilizing the Newcastle Ottawa Scale and Cochrane's Risk of Bias assessment tool 2.0. The review provided both a qualitative and quantitative analysis of the results. A random effects model was used for meta-analysis. RESULTS: Twenty-five studies were included (5 randomized controlled trials, 20 non-randomized controlled trials). Overall, risk of bias was low. Compared with the contralateral side or controls, there were significant alterations in somatosensory function of the surgical site in PPSP-patients. Following thresholds were significantly increased: mechanical detection thresholds for punctate stimuli (mean difference (95% CI) 3.3 (1.6, 6.9) mN (P = 0.002)), warmth detection thresholds (3.2 (1.6, 4.7) °C (P = 0.0001)), cool detection thresholds (-3.2 (-4.9, -1.6) °C (P = 0.0001)), and heat pain thresholds (1.9 (1.1, 2.7) °C (P = 0.00001)). However, the pressure pain thresholds were significantly decreased (-76 (-123, -30) kPa (P = 0.001)). CONCLUSION: Our review demonstrates a plethora of methods used regarding outcome assessments, data processing, and data interpretation. From a pathophysiological perspective, the most consistent findings were postsurgical cutaneous deafferentation and development of a pain generator in deeper connective tissues. TRIAL REGISTRATION: CRD42022331750.

Effect of a Nurse Navigation Intervention on Mental Symptoms in Patients With Psychological Vulnerability and Breast Cancer: The REBECCA Randomized Clinical Trial.

Importance: The unmet needs regarding symptom management of psychological distress among patients with breast cancer must be addressed. However, little evidence exists on effective interventions, such as nurse navigation. Objective: To compare the long-term effects of the REBECCA (Rehabilitation After Breast Cancer) nurse navigation intervention vs usual care in patients with breast cancer who were psychologically vulnerable. Design, Setting, and Participants: This parallel randomized clinical trial recruited and evaluated for eligibility adult female patients with newly diagnosed breast cancer and symptoms of psychological distress (distress score of ≥7 points on Distress Thermometer) at Rigshospitalet in Copenhagen, Denmark, from August 2017 to October 2019. This study continued the work of a pilot study, extending the follow-up to 18 months. Patients who met the inclusion criteria were randomized to either standard care or the REBECCA intervention. Intention-to-treat analyses were performed from June 2021 to October 2022. Interventions: Patients who were randomized to the REBECCA intervention received nurse navigation and symptom screening as well as standard care. Standard care included regular treatment, nurse support at chemotherapy and radiotherapy appointments, and municipality-based rehabilitation. Main Outcomes and Measures: The primary outcome was distress, as measured using the Distress Thermometer. The secondary outcomes included symptoms of anxiety, symptoms of depression, breast cancer-specific health-related quality of life, fear of recurrence, sleep, cognitive function, patient activation, pain, health behavior, body mass index, and need for support. Long-term effects at 6, 12, and 18 months were examined using mixed-effect models, adjusting for randomization strata of age and treatment modality. Results: A total of 309 female patients were included in the analysis, with 153 patients randomized to the standard care group and 156 patients randomized to the REBECCA intervention group. Mean (SD) age was 56 (11) years with only small between-group differences. Patients receiving the REBECCA intervention compared with standard care had reduced (although not significant) symptoms of distress, especially at the 12-month follow-up (estimated effect = -0.51 [95% CI, -1.05 to 0.04]; effect size [ES] = -0.49). Significant effects were seen for symptoms of depression at 6 months (estimated effect = -1.39 [95% CI, -2.33 to -0.44]; ES = -0.27), and breast cancer-specific health-related quality of life at 12 months (estimated effect = 4.03 [95% CI, 1.28- 6.77]; ES = 0.31). Nonsignificant reductions were seen for symptoms of anxiety at 6 months (estimated effect = -1.00 [95% CI, -1.95 to -0.06]; ES = -0.21) and 12 months (estimated effect = -1.01 [95% CI, -1.97 to -0.04]; ES = -0.21), and a nonsignificant increase was seen for patient activation at 18 months (estimated effect = 3.52 [95% CI, -0.09 to 7.12]; ES = 0.25). Stronger intervention effects were observed for younger age, low patient activation, less education, and low social support. Conclusions and Relevance: Results of this study indicate that patients with breast cancer who were psychologically vulnerable (ie, having moderate to high psychological distress) did not experience significant reduction in distress with nurse navigation. Further research is needed to develop the intervention's framework and investigate its potential use in clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03254875.

Long-term results of a standardized enhanced recovery protocol in unilateral, secondary autologous breast reconstructions using an abdominal free flap.

BACKGROUND: In 2015, we published one of the first reports using an enhanced recovery protocol (ERP) in microsurgery1, and in 2016, our final ERP setup in autologous breast reconstruction (ABR) using free abdominal flaps2. We showed that by adhering to a few simple, easy to measure, functional discharge criteria, it was possible to safely discharge the patients by the third postoperative day (POD). However, one of the challenges of interpreting studies using ERP in ABR is the often heterogenous patient populations and the need to clearly distinguish between primary and secondary and unilateral and bilateral reconstructions. MATERIALS AND METHODS: In the 5-year period from 2016-2020, the same surgical team, performed 147 unilateral, delayed breast reconstructions (135 DIEP, 9 MS-TRAM-2, and 3 SIEA flaps) according to our previous analgesic protocol and surgical strategy. Data were collected prospectively. RESULTS: Three flaps were lost (2%) and 82% of the patients(n=128) were discharged to home by POD 2 (n=8%) or 3 (74%). The remaining 18% (n=26) were discharged by POD 4 (12.5%) or 5 (5.5%). Ten patients (7%) were reoperated, and 17 patients (12%) had minor complications within POD 30 (infection, seroma, etc.) that did not necessitate hospital admission. CONCLUSION: Using our ERP, unproblematic discharge directly to home is possible on POD 3 in more than 80% of patients after ABR. ERP is no longer a research tool but considered standard of care in microsurgical breast reconstruction.

Use of Medical Supplies at the Roskilde Festival 2016: A Prospective Observational Study.

INTRODUCTION: Music festivals are popular events often including camping at the festival site. A mix of music, alcohol, drugs, and limited hygiene increases health risks. This study aimed to assess the use of medical supplies at a major music festival, thereby aiding planning at similar events in the future. METHOD: The Medical Health Care Organization (MHCO) at Roskilde Festival 2016 (Denmark) collected prospective data on disposable medical supply use and injuries and illnesses presenting to the MHCO. RESULTS: A total of 12,830 patient presentations were registered by the MHCO and a total of 104 different types of disposable medical supplies were used by the MHCO from June 25, 2016 through July 3, 2016. Out of 12,830 cases, 594 individuals (4.6%) had a potential or manifest medical emergency, 6,670 (52.0%) presented with minor injuries, and 5,566 (43.4%) presented with minor illnesses. The overall patient presentation rate (PPR) was 99.0/1,000 attendees and the transport-to-hospital rate (TTHR) was 2.1/1,000 attendees. For medical emergencies, the most frequently used supplies were aluminum rescue blankets (n = 627), non-rebreather masks (n = 121), and suction catheters for an automatic suction unit (ASU) for airway management (n = 83). Most used diagnostic equipment were blood glucose test strips (n = 1,155), electrocardiogram electrodes (n = 960), and urinary test strips (n = 400). The most frequently used personal protection equipment were non-sterile gloves (n = 1,185 pairs) and sterile gloves (n = 189). CONCLUSION: This study demonstrates a substantial use of disposable medical supplies at a major music festival. The results provide aid for planning similar mass-gathering (MG) events.

A Dual-Frequency Coupled Resonator Transducer.

New ultrasound-mediated drug delivery systems, such as acoustic cluster therapy or combined imaging and therapy systems, require transducers that can operate beyond the bandwidth limitation (~100%) of conventional piezoceramic transducers. In this article, a dual-frequency coupled resonator transducer (CRT) comprised of a polymeric coupling layer with a low acoustic impedance (2-5 MRayl) sandwiched between two piezoceramic layers is investigated. Depending on the electrical configuration, the CRT exhibits two usable frequency bands. The resonance frequency of the high-frequency (HF) band can be tailored to be ~3-5 times higher than that of the low-frequency (LF) band using the stiffness in the coupling layer. The CRT's LF band was analyzed analytically, and we obtained the closed-form expressions for the LF resonance frequency. A dual-frequency CRT was designed, manufactured, and characterized acoustically, and comparisons with theory showed good agreement. The HF band exhibited a center frequency of 2.5 MHz with a -3-dB bandwidth of 70% and is suited to manipulate microbubbles or for diagnostic imaging applications. The LF band exhibited a center frequency of 0.5 MHz with a -3-dB bandwidth of 13% and is suited to induce biological effects in tissue, therein manipulation of microbubbles.

Deficiency of T-type voltage-gated calcium channels results in attenuated weight gain and improved endothelium-dependent dilatation of resistance vessels induced by a high-fat diet in mice.

The deletion of T-type Cav3.1 channels may reduce high-fat diet (HFD)-induced weight gain, which correlates positively with obesity and endothelial dysfunction. Therefore, experiments were designed to study the involvement of T-type Cav3.1 channels in HFD-induced endothelial dysfunction in mice. Wildtype (WT) and Cav3.1-/- mice were fed either a normal diet (ND) or an HFD for 8 weeks. Body composition was assessed, and thoracic aortae and mesenteric arteries were harvested for myography to assess endothelium-dependent responses. Changes in intracellular calcium were measured by fluorescence imaging, and behavior was assessed with the open-field test. Cav3.1-/- mice had attenuated HFD-induced weight gain and lower total fat mass compared with WT mice. Cav3.1-/- mice on an HFD had reduced plasma cholesterol levels compared with WT mice on the same diet. Increased feeding efficiency, independent of food intake, was observed in WT mice on an HFD compared with an ND, but no difference in feeding efficiency between diets was observed for Cav3.1-/- mice. Nitric oxide-dependent dilatation was increased in mesenteric arteries of Cav3.1-/- mice compared with WT mice on an HFD, with no difference observed in aortae. No differences in mouse locomotor activity were observed between the experimental groups. Mice on an HFD lacking T-type channels have reduced weight gain, lower total cholesterol levels, and increased dilatation of resistance vessels compared with WT mice on an HFD, suggesting that Cav3.1 deletion protects against endothelial dysfunction in resistance vessels but not in large conduit vessels.

Effect of progressive resistance training on persistent pain after axillary dissection in breast cancer: a randomized controlled trial.

PURPOSE: Persistent pain is a known challenge among breast cancer survivors. In secondary analyses of a randomized controlled trial, we examined the effect of progressive resistance training on persistent pain in the post-operative year in women treated for breast cancer with axillary lymph node dissection. METHODS: We randomized 158 women after BC surgery with Axillary Lymph Node Dissection (ALND) (1:1) to usual care or a 1-year, supervised and self-administered, progressive resistance training intervention initiated 3 weeks after surgery. A questionnaire at baseline, 20 weeks and 12 months assessed the intensity and frequency of pain, neuropathic pain and influence of pain on aspects of daily life. We analysed the effect using linear mixed models and multinomial logistic regression models for repeated measures. RESULTS: A high percentage of participants experienced baseline pain (85% and 83% in the control and intervention groups respectively) and by the 12 month assessment these numbers were more than halved. A high proportion of participants also experienced neuropathic pain (88% and 89% in control and intervention group respectively), a finding that was stable throughout the study period. The effect on intensity of pain indicators favoured the exercise group, although most estimates did not reach statistical significance, with differences being small. CONCLUSION: For women who had BC surgery with ALND, our progressive resistance training intervention conferred no benefit over usual care in reducing pain. Importantly, it did not increase the risk of pain both in the short and long term rehabilitative phase.

Use of Medication at the Roskilde (Denmark) Music Festival 2015 - A Prospective Observational Study of 15,133 Treated Attendees.

BACKGROUND: Outdoor music festivals (OMFs) attract large numbers of guests and benefit from the help of large numbers of volunteers. Studies have previously described the injury patterns at OMFs, but no studies have described the use of medication and sales from on-site pharmacies at a large OMF. METHOD: The usage of medication and prescriptions in the Medical Health Care Organization (MHCO), including sales from the on-site pharmacy, at the Roskilde (Denmark) Festival 2015 were prospectively recorded. RESULTS: In excess of 130,000 attendees (guests and volunteers) participated in the Roskilde Festival 2015. The number of attendees contacting the MHCO was 15,133, of which 3,723 (25%) had a consultation with a doctor. Of all attendees evaluated by a doctor, 669 attendees received some form of medication in relation to the consultation. The MHCO administered and/or handed out a total of 6,494 units of prescription and over-the-counter medication, of which analgesics represented nearly 51%. Asthma was the condition with the highest proportion of attendees requiring pharmaceutical treatment, as 28 out of 48 (58%) received medication during the consultation. Sixty-five attendees received both medicine and a prescription. The MHCO handed out 562 prescriptions. In total, 609 prescriptions were redeemed at the on-site pharmacy. Antibiotics represented more than 78% of all redeemed prescriptions at the on-site pharmacy. CONCLUSION: The most utilized medications were analgesics and antibiotics. The data indicate a need for on-site prophylaxis using tetanus toxoid in combination with diphtheria toxoid vaccine and an on-site pharmacy. The content of the formulary at a mass-gathering event should be based on: evacuation time by ambulance/helicopter to hospitals with the level of competence needed; types of conditions to be treated on-site; level of competencies of festival medical staff; expected incidence and type of illness and injuries; and treatment of acute, life-threatening illnesses and or injuries.

A Harmonic Dual-Frequency Transducer for Acoustic Cluster Therapy.

Acoustic Cluster Therapy (ACT) is a two-component formulation of commercially available microbubbles (Sonazoid; GE Healthcare, Oslo, Norway) and microdroplets (perfluorated oil) currently under development for cancer treatment. The microbubbles and microdroplets have opposite surface charges to form microbubble/microdroplet clusters, which are administered to patients together with a drug. When the clusters and drug reach the target tumour, two ultrasound (US) exposure regimes are used: First, high-frequency (>2.0 MHz) US evaporates the oil and forms ACT bubbles that lodge at the microvascular level. Second, low-frequency (0.5 MHz) US induces stable mechanical oscillations of the ACT bubbles, causing localized micro-streaming, radiation and shear forces that increase the uptake of the drugs to the target tumour. This report describes the design and testing of a dual-frequency transducer and a laboratory setup for pre-clinical in vivo studies of ACT on murine tumour models. The dual-frequency transducer utilizes the 5th harmonic (2.7 MHz) and fundamental (0.5 MHz) of a single piezoceramic disk for the high-frequency and low-frequency regimes, respectively. Two different aperture radii are used to align the high-frequency and low-frequency beam maxima, and the high-frequency -3 dB beam width diameter is 6 mm, corresponding to the largest tumour sizes we expect to treat. The low-frequency -3 dB beam width extends 6 mm. Although unconventional, the 5th harmonic exhibit a 44% efficiency and can therefore be used for transmission of acoustic energy. Moreover, both in vitro and in vivo measurements demonstrate that the 5th harmonic can be used to evaporate the microbubble/microdroplet clusters. For the in vivo measurements, we used the kidneys of non-tumour-bearing mice as tumour surrogates. Based on this, the transducer is deemed suited for pre-clinical in vivo studies of ACT and replaces a cumbersome test setup consisting of two transducers.

Development and Validation of a Screening Tool for Surgery-Specific Neuropathic Pain: Neuropathic Pain Scale for Postsurgical Patients.

BACKGROUND: Despite the existence of several screening tools for neuropathic pain, none of these are specific to surgery. We have developed a simple questionnaire tool, the Neuropathic Pain scale for Postsurgical patients (NeuPPS), to measure neuropathic pain in postsurgical patients. OBJECTIVES: The aim was to validate this tool in a breast cancer population using an item response theory model, resulting in an easy-to-use scale. STUDY DESIGN: Development was based on literature reviews and interviews with patients and experts and consisted of 6 items. It was tested among 2,217 long-term breast cancer survivors, and cross-validated in another data set of breast cancer survivors with 18 months follow-up. SETTING: We tested the questionnaire tool among breast cancer survivors in 2 cohorts, one nationwide and one of consecutively treated patients at Rigshospitalet, Copenhagen, Denmark. METHODS: Items were assessed for criterion-related construct validity using the Rasch model, and for convergent validity by comparison to another neuropathic pain screening tool, the self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain scale. RESULTS: The selected 5-item model showed good fit, unidimensionality, monotonicity, and homogeneity. This result was reproducible in the cross-validation population. In a combined dataset with data from both studies, the model displayed a slightly lower fit, suggesting that items to some degree may vary over time. The Spearman rank correlation between the NeuPPS and S-LANSS was P = 0.57. LIMITATIONS: We observed differential item functioning between the primary study population and the cross-validation population, meaning that some items behave differently at different follow-up times or study populations. CONCLUSIONS: With the NeuPPS, we have validated a simple and easy-to-fill-out questionnaire tool for the measurement of neuropathic pain among postsurgical patients. The items are additive, giving a total score that measures neuropathic pain symptoms. KEY WORDS: Scale validation, Rasch analysis, item response model, persistent postoperative pain, intercostobrachial nerve, neuropathy, neuropathic pain, quantitative sensory testing, breast cancer.

A Numerical Optimization Method for Transducer Transfer Functions by the Linearity of the Phase Spectrum.

New ultrasound imaging and therapeutic modalities may require transducer designs that are not readily facilitated by conventional design guidelines and analytical expressions. This motivates the investigation of numerical methods for complex transducer structures. Based on a mathematical theorem, we propose a new numerical design and optimization method for ultrasound transducers by linearizing the phase spectrum of transducer transfer functions. A gradient-based algorithm obtains the optimal transducer by varying a selected set of transducer parameters. To demonstrate the linear phase method, a simulated air-backed 4-MHz single-element imaging transducer with two matching layers, bondlines, and electrodes is optimized by varying the impedances and thicknesses of the matching layers. The magnitude spectrum resembles that of a Gaussian and, compared to a conventional transducer, the time-sidelobe level is reduced by more than 15-dB. Moreover, we apply the linear phase method to analyze and compensate for bondlines that resonate within the passband. Finally, we address the challenge of obtaining materials for the matching layers with the optimized impedance values by calculating alternative material pairs.

Identification of protein phosphatase involvement in the AT2 receptor-induced activation of endothelial nitric oxide synthase.

The Angiotensin II type 2 receptor (AT2R) promotes vasodilation by nitric oxide (NO) release from endothelial cells. However, the mechanisms underlying the AT2R-induced stimulation of endothelial NO synthase (eNOS) is still not completely understood. Therefore, we investigated whether in addition to the known AT2R-mediated phosphorylation of eNOS at Ser1177, activation of phosphatases and dephosphorylation of eNOS at Tyr657 and Thr495 are also involved. Human aortic endothelial cells (HAEC) were stimulated with the AT2R-agonist Compound 21 (C21) (1 µM) in the presence or absence of either PD123319 (10 µM; AT2R antagonist), l-NG-Nitroarginine methyl ester (l-NAME) (10 µM; eNOS inhibitor), MK-2206 (100 nM; protein kinase B (Akt) inhibitor) sodium fluoride (NaF) (1 nM; serine/threonine phosphatase inhibitor) or sodium orthovanadate (Na3VO4) (10 nM; tyrosine phosphatase inhibitor). NO release was estimated by quantifying 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM) fluorescence. The phosphorylation status of activating (eNOS-Ser1177) or inhibitory eNOS residues (eNOS-Tyr657, eNOS-Thr495) was determined by Western blotting. Phosphorylation of Akt at Ser473 was measured to estimate Akt activity. AT2R stimulation significantly increased NO release from HAEC, which was blocked by PD123319, l-NAME and both phosphatase inhibitors. Intracellular calcium transients were not changed by C21. AT2R stimulation resulted in phosphorylation of eNOS-Ser1177 and dephosphorylation of eNOS-Tyr657 and eNOS-Thr495 Phosphorylation at eNOS-Ser1177 was prevented by inhibition of Akt with MK-2206. From these data, we conclude that AT2R stimulation in human endothelial cells increases eNOS activity through phosphorylation of activating eNOS residues (eNOS-Ser1177) by Akt, and through dephosphorylation of inactivating eNOS residues (eNOS-Tyr657, eNOS-Thr495) by serine/threonine and tyrosine phosphatases, thus increasing NO release.

Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice.

Impairment of endothelial function with aging is accompanied by reduced nitric oxide (NO) production. T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels contribute to the endothelial dysfunction of aging. Endothelial function was determined in mesenteric arteries (perfusion) and aortae (isometric contraction) of young and old wild-type (WT), Cav3.1, and Cav3.2 knockout mice. NO production was measured by fluorescence imaging in mesenteric arteries. With age, endothelium-dependent subsequent dilatation (following depolarization with KCl) of mesenteric arteries was diminished in the arteries of WT mice, unchanged in Cav3.2-/- preparations but increased in those of Cav3.1-/- mice. NO synthase inhibition abolished the subsequent dilatation in mesenteric arteries and acetylcholine-induced relaxations in aortae. NO levels were significantly reduced in mesenteric arteries of old compared to young WT mice. In Cav3.1-/- and Cav3.2-/- preparations, NO levels increased significantly with age. Relaxations to acetylcholine were significantly smaller in the aortae of old compared to young WT mice, while such responses were comparable in preparations of young and old Cav3.1-/- and Cav3.2-/- mice. The expression of Cav3.1 was significantly reduced in aortae from aged compared to young WT mice. The level of phosphorylated eNOS was significantly increased in aortae from aged Cav3.1-/- mice. In conclusion, T-type calcium channel-deficient mice develop less age-dependent endothelial dysfunction. Changes in NO levels are involved in this phenomenon in WT and Cav3.1-/- mice. These findings suggest that T-type channels play an important role in age-induced endothelial dysfunction.

The effects of individually tailored nurse navigation for patients with newly diagnosed breast cancer: a randomized pilot study.

AIM: Our aim was to determine the feasibility and effectiveness of an individual, nurse-navigator intervention for relieving distress, anxiety, depression and health-related quality of life in women who have been treated for breast cancer (BC) and are experiencing moderate-to-severe psychological and physical symptoms. METHODS: Fifty women with newly diagnosed BC who reported distress (score ≥7 on distress thermometer) before surgery were included consecutively in a pilot study and randomized 1:1 to the intervention or the control group. The intervention comprised repeated screening with patient reported outcome measures and nurse navigation. A total of 66 women who were not distressed (score <7) were followed longitudinally as an observational group. Participants filled in four questionnaires, at baseline, after 6 months and 12 months. The primary outcome was psychological distress and the secondary outcomes were anxiety, depression, health-related quality of life and feasibility of the intervention. RESULTS: Women in the intervention group reported significantly greater satisfaction with treatment and rehabilitation and lower levels of distress (mean 2.7 vs. 5.1, p<.01), anxiety (mean 5.1 vs. 7.8, p = .02) and depression (mean 2.2 vs. 4.4, p = .04) after 12 months compared to the control group. No significant effects were seen on health-related quality of life. CONCLUSIONS: The study shows promising feasibility of the individually tailored nurse-navigation intervention and while no significant effects were observed after 6 months, we did find statistically significant effects on distress, anxiety and depression 12 months after diagnosis. Our results will assist in developing rehabilitation to the most vulnerable patients.

Pain, Sensory Disturbances, and Psychological Distress among Danish Women Treated for Ductal Carcinoma In Situ: An Exploratory Study.

Ductal carcinoma in situ is a noninvasive precancer condition. The treatment resembles the treatment of invasive breast cancer. The aim of this exploratory study was to gain knowledge on the level of postoperative pain, sensory disturbances, and distress among a small group of Danish women with ductal carcinoma in situ who had sentinel lymph node biopsy in order to plan a population study. A subgroup of patients with ductal carcinoma in situ (n = 20) was compared to patients with invasive breast cancer (n = 455) at time of diagnosis and after 12 months. Six patients were interviewed on the impact of the diagnosis and life after treatment. We found no significant difference in reported sensory disturbances or pain after 12 months between the groups. More than one-third (39%) of ductal carcinoma in situ patients reported moderate to severe distress (≥ 7 on the Distress Thermometer) at time of diagnosis decreasing to 10% after 12 months. Similarly 36% of breast cancer patients reported distress at time of diagnosis and 10% after 12 months. Interviews confirmed that ductal carcinoma in situ patients experienced distress and also uncovered physical problems and rehabilitation needs. The study indicates that women with ductal carcinoma in situ seem to suffer from pain and distress. The study highlights the need for a large study in order to validate the findings. Additional efforts may be needed to improve patients' understanding of diagnosis of ductal carcinoma in situ and alleviate psychological morbidity and physical restraints related to the condition.

The Relationship Between Sensory Loss and Persistent Pain 1 Year After Breast Cancer Surgery.

Moderate to severe persistent pain after breast cancer surgery (PPBCS) affects 10 to 20% of the patients. Sensory dysfunction is often concomitantly present suggesting a neuropathic pain state. The relationship between various postoperative pain states and sensory dysfunction has been examined using quantitative sensory testing (QST), but only 2 smaller studies have examined PPBCS and sensory dysfunction in the surgical area. The purpose of this prospective study was to assess the relative importance of sensory function and PPBCS. QST consisted of sensory mapping, tactile detection threshold, mechanical pain threshold, and thermal thresholds. Two hundred ninety patients were enrolled and results showed that 38 (13%) had moderate to severe pain and 246 (85%) had hypoesthesia in the surgical area 1 year after surgery. Increased hypoesthesia areas were associated with pain at rest as well as during movement (P = .0001). Pain during movement was associated with a side-to-side difference of 140% (P = .001) for tactile detection threshold and 40% (P = .01) for mechanical pain threshold as well as increased thermal thresholds in the axilla (P > .001). Logistic regression models controlling for confounders showed larger areas of hypoesthesia as a significant risk factor, odds ratio 1.85 per 100 cm2 for pain at rest and odds ratio 1.36 per 100 cm2 for pain during movement. PERSPECTIVE: PPBCS is associated with increasing areas of hypoesthesia as well as intraoperative nerve preservation. Thus, we hypothesize that PPBCS is associated with an interaction between a peripheral nociceptive drive in macroscopically preserved nerves and the central nervous system causing PPBCS as well as hypoesthesia. QST may identify patients suitable for intervention.

Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery.

Purpose Persistent pain after breast cancer surgery is a well-recognized problem, with moderate to severe pain affecting 15% to 20% of women at 1 year from surgery. Several risk factors for persistent pain have been recognized, but tools to identify high-risk patients and preventive interventions are missing. The aim was to develop a clinically applicable risk prediction tool. Methods The prediction models were developed and tested using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231). Prediction models for persistent pain of moderate to severe intensity at 1 year postoperatively were developed by logistic regression analyses in the Finnish patient cohort. The models were tested in two independent cohorts from Denmark and Scotland by assessing the areas under the receiver operating characteristics curves (ROC-AUCs). The outcome variable was moderate to severe persistent pain at 1 year from surgery in the Finnish and Danish cohorts and at 9 months in the Scottish cohort. Results Moderate to severe persistent pain occurred in 13.5%, 13.9%, and 20.3% of the patients in the three studies, respectively. Preoperative pain in the operative area ( P < .001), high body mass index ( P = .039), axillary lymph node dissection ( P = .008), and more severe acute postoperative pain intensity at the seventh postoperative day ( P = .003) predicted persistent pain in the final prediction model, which performed well in the Danish (ROC-AUC, 0.739) and Scottish (ROC-AUC, 0.740) cohorts. At the 20% risk level, the model had 32.8% and 47.4% sensitivity and 94.4% and 82.4% specificity in the Danish and Scottish cohorts, respectively. Conclusion Our validated prediction models and an online risk calculator provide clinicians and researchers with a simple tool to screen for patients at high risk of developing persistent pain after breast cancer surgery.

Pain, sensory disturbances and psychological distress are common sequelae after treatment of ductal carcinoma in situ: a cross-sectional study.

Sequelae such as pain, sensory disturbances and psychological distress are well known after treatment for invasive breast cancer (IBC). Patients treated for ductal carcinoma in situ (DCIS) receive a similar treatment as low-risk IBC. The aim of this cross-sectional study was to describe prevalence of postoperative pain, sensory disturbances, psychological distress and rehabilitation needs among Danish women with DCIS. METHODS: A total of 574 women treated for DCIS in Denmark in 2013 and 2014 were enrolled and 473 (82%) completed a detailed questionnaire on demographic factors, pain, sensory disturbances, psychological aspects and rehabilitation needs 1-3 years after surgery. RESULTS: Median age was 60 years. A total of 33% of patients reported any pain and 12% reported moderate to severe pain in the area of surgery. Younger age (<50 years OR 4.7 (95% CI: 1.6-14.0, p = 0.006)), aged 50 to 65 years OR 2.8 (95% CI: 1.1-7.0, p = 0.02) and anxiety and depression (measured by HADStotal >15 OR of 3.1 (95% CI: 1.5-6.3, p = 0.003)) were significantly associated with moderate to severe pain. Approximately one-third of the patients reported sensory disturbances such as pins and needles (32%), numbness (37%) and painful itch (30%) and 94 women (20%) reported anxiety ≥8, 26 (6%) depression and 51 (11%) reported distress. CONCLUSIONS: This cross-sectional study showed that women treated for DCIS suffered from pain, sensory disturbances and psychological impairment and had unmet rehabilitation needs. Further research is warranted, specifically addressing rehabilitation after diagnosis and treatment of DCIS.

Analgesic and Sensory Effects of the Pecs Local Anesthetic Block in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study.

BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) develops in 15% to 25% of patients, sometimes years after surgery. Approximately 50% of PPBCS patients have neuropathic pain in the breast, which may be due to dysfunction of the pectoral nerves. The Pecs local anesthetic block proposes to block these nerves and has provided pain relief for patients undergoing breast cancer surgery, but has yet to be evaluated in patients with PPBCS. METHODS: The aim of this pilot study was to examine the effects of the Pecs block on summed pain intensity (SPI) and sensory function (through quantitative sensory testing [QST]) in eight patients with PPBCS. SPI and QST measurements were recorded before and 30 minutes after administration of the Pecs block (20 mL 0.25% bupivacaine). Pain intensity and sleep interference were measured daily before and after the block for 7 days. RESULTS: Patients experienced analgesia (P = 0.008) and reduced hypoesthesia areas to cold (P = 0.004) and warmth (P = 0.01) after 30 minutes. The reported pain relief (P = 0.02) and reduced sleep interference (P = 0.01) persisted for 7 days after the block. CONCLUSIONS: This pilot study suggests that the pectoral nerves play a role in the maintenance of pain in the breast area in PPBCS and begs for further research.