Does psychological distress predict risk of orthopaedic surgery and postoperative opioid prescribing in patients with hip pain? A retrospective study.

BACKGROUND: Clinicians and public health professionals have allocated resources to curb opioid over-prescription and address psychological needs among patients with musculoskeletal pain. However, associations between psychological distress, risk of surgery, and opioid prescribing among those with hip pathologies remain unclear. METHODS: Using a retrospective cohort study design, we identified patients that were evaluated for hip pain from January 13, 2020 to October 27, 2021. Patients' surgical histories and postoperative opioid prescriptions were extracted via chart review. Risk of hip surgery within one year of evaluation was analyzed using multivariable logistic regression. Multivariable linear regression was employed to predict average morphine milligram equivalents (MME) per day of opioid prescriptions within the first 30 days after surgery. Candidate predictors included age, gender, race, ethnicity, employment, insurance type, hip function and quality of life on the International Hip Outcome Tool (iHOT-12), and psychological distress phenotype using the OSPRO Yellow Flag (OSPRO-YF) Assessment Tool. RESULTS: Of the 672 patients, n = 350 (52.1%) underwent orthopaedic surgery for hip pain. In multivariable analysis, younger patients, those with TRICARE/other government insurance, and those with a high psychological distress phenotype had higher odds of surgery. After adding iHOT-12 scores, younger patients and lower iHOT-12 scores were associated with higher odds of surgery, while Black/African American patients had lower odds of surgery. In multivariable analysis of average MME, patients with periacetabular osteotomy (PAO) received opioid prescriptions with significantly higher average MME than those with other procedures, and surgery type was the only significant predictor. Post-hoc analysis excluding PAO found higher average MME for patients undergoing hip arthroscopy (compared to arthroplasty or other non-PAO procedures) and significantly lower average MME for patients with public insurance (Medicare/Medicaid) compared to those with private insurance. Among those only undergoing arthroscopy, older age and having public insurance were associated with opioid prescriptions with lower average MME. Neither iHOT-12 scores nor OSPRO-YF phenotype assignment were significant predictors of postoperative mean MME. CONCLUSIONS: Psychological distress characteristics are modifiable targets for rehabilitation programs, but their use as prognostic factors for risk of orthopaedic surgery and opioid prescribing in patients with hip pain appears limited when considered alongside other commonly collected clinical information such as age, insurance, type of surgery pursued, and iHOT-12 scores.

Rapid onset pembrolizumab-induced inflammatory arthritis diagnosed using musculoskeletal ultrasound.

Immune checkpoint inhibitors have revolutionised the treatment of cancer. While very effective, they commonly cause a wide spectrum of immune-related adverse events. These immune-related adverse events can be fatal and often have significant effects on quality of life. They therefore require prompt recognition and management. We report the case of a woman presenting with widespread joint pain and stiffness 6 hours after her first pembrolizumab infusion. She had no joint swelling on physical examination but an ultrasound scan revealed widespread musculoskeletal inflammation, confirming the diagnosis of inflammatory arthritis. To the best of our knowledge, this is the fastest reported inflammatory arthritis onset following immune checkpoint inhibitor treatment. It highlights the importance of timely imaging in patients on immune checkpoint inhibitors who present with new non-specific musculoskeletal pain. Her symptoms improved dramatically with intramuscular triamcinolone injection.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial.

PURPOSE: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain. METHODS: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3. RESULTS: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms. CONCLUSION: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA. CLINICALTRIALS: gov Identifier: NCT03865992, first posted March 7, 2019.

TET1-mediated epigenetic regulation of tumor necrosis factor-α in trigeminal ganglia contributes to chronic temporomandibular joint pain.

Chronic temporomandibular joint (TMJ) pain profoundly affects patients' quality of life. Trigeminal tumor necrosis factor-α (TNFα) plays a pivotal role in mediating TMJ pain in mice, yet the underlying epigenetic mechanisms remain enigmatic. To unravel these epigenetic intricacies, we employed a multifaceted approach. Hydroxymethylated DNA immunoprecipitation (hMeDIP) and chromatin immunoprecipitation (ChIP) followed by qPCR were employed to investigate the demethylation of TNFα gene (Tnfa) and its regulation by ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in a chronic TMJ pain mouse model. The global levels of 5-hydroxymethylcytosine (5hmc) and percentage of 5hmc at the Tnfa promoter region were measured in the trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) following complete Freund's adjuvant (CFA) or saline treatment. TET1 knockdown and pain behavioral testing were conducted to ascertain the role of TET1-mediated epigenetic regulation of TNFα in the pathogenesis of chronic TMJ pain. Our finding revealed an increase in 5hmc at the Tnfa promoter region in both TG and Sp5C of CFA-treated mice. TET1 was upregulated in the mouse TG, and the ChIP result showed TET1 direct binding to the Tnfa promoter, with higher efficiency in the CFA-treated group. Immunofluorescence revealed the predominant expression of TET1 in trigeminal neurons. TET1 knockdown in the TG significantly reversed CFA-induced TNFα upregulation and alleviated chronic TMJ pain. In conclusion, our study implicates TET1 as a vital epigenetic regulator contributing to chronic inflammatory TMJ pain via trigeminal TNFα signaling. Targeting TET1 holds promise for epigenetic interventions in TMJ pain management.

Effect of whole-body cryotherapy versus placebo cryotherapy on joint pain induced by aromatase inhibitors in women with early stage breast cancer: a randomised clinical trial.

INTRODUCTION: Hormone therapy (HT) is a major adjuvant treatment for breast cancer. Despite their effectiveness, aromatase inhibitors can cause several side effects, including arthralgia in 35%-50% of patients. These side effects frequently lead to the premature discontinuation of HT. Whole-body cryotherapy (WBC) can be used for managing arthritic pain. The primary objective of this study will be to evaluate the effect of WBC on aromatase-induced joint pain, compared with placebo cryotherapy, in patients with hormone-dependent breast cancer receiving adjuvant aromatase inhibitors. The secondary objectives will be to evaluate WBC safety and its effect on analgesic consumption, HT adherence and quality of life. METHODS AND ANALYSIS: In this randomised, placebo-controlled, double-blinded clinical trial, 56 patients with aromatase inhibitor-induced joint pain and a Brief Pain Inventory-Short Form (BPI-SF) score ≥3 for the worst pain experienced in the previous week will be randomised into the WBC or placebo cryotherapy arm (10 sessions in each group). The primary outcome will be the BPI-SF score at week 6 post-treatment. The secondary outcomes will include the BPI-SF scores at months 3 and 6 post-treatment, the BPI-SF pain severity index and pain interference index, the Health Assessment Questionnaire score, the number of days of aromatase inhibitor treatment and analgesic consumption in the 15 days before the visits at week 6 and months 3 and 6 after cryotherapy. The incidence of adverse events will also be investigated. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee Est IV of Hospital Civil, Strasbourg, France. Protocol V.5 was approved in December 2022. The results will be disseminated in a peer-reviewed journal and presented at international congresses. TRIAL REGISTRATION NUMBER: NCT05315011.

The lived experience of patients with breast cancer on adjuvant endocrine therapy: side effects and coping strategies during the first year of medication initiation.

PURPOSE: Adjuvant endocrine therapy (AET) is pivotal for hormone receptor-positive breast cancer patients, significantly enhancing survival rates. Yet, adherence to AET remains challenging due to side effects. This study delves into the lived experience of breast cancer survivors concerning AET-induced side effects and examines differences in symptom profiles between Tamoxifen and aromatase inhibitors (AIs). METHODS: We interviewed 35 breast cancer survivors on AET, conducting qualitative iterative analysis using grounded theory. A codebook was developed to aid data coding and interpretation. NVIVO software facilitated comprehensive transcript analysis. RESULTS: Survivors reported a spectrum of side effects like hot flashes, sexual issues, joint pain, stiffness, mood swings, and fertility concerns. Symptom profiles differed based on AET type. Tamoxifen users experienced more frequent sexual side effects and mood swings, while AIs were linked to joint pain, stiffness, and bone health worries. Those on AET for over 6 months expressed heightened concerns about side effects. CONCLUSION: Tailored patient education, aligned with AET type, empowers survivors to manage side effects using self-regulatory strategies. Acknowledging distinct symptom profiles enables informed decisions, improving adherence and quality of life. IMPLICATIONS: This study underscores tailored survivorship support, equipping patients with tools to manage side effects, enhancing adherence, and long-term outcomes. The findings inform the integration of comprehensive survivorship programs, emphasizing individualized strategies for managing side effects and promoting better adherence and improved quality of life.

Impact of CDK4/6 Inhibitors on Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS) in the Adjuvant Setting.

Background: Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a well-tolerated therapy, AI-induced musculoskeletal symptoms are common and may be accused for treatment discontinuation. Recently, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors changed the therapeutic setting, and currently, ribociclib, palbociclib, and abemaciclib are all approved in combination with nonsteroidal AIs in patients with ER-positive, HER2-negative advanced or metastatic breast cancer. This systematic review aims to identify the frequency of aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) in the adjuvant setting in patients under AI monotherapy compared to patients under combination therapy with AIs and CDK4/6 inhibitors and demonstrate the underlying mechanism of action. Methods: This study was performed in accordance with PRISMA guidelines. The literature search and data extraction from all randomized clinical trials (RCTs) were done by two independent investigators. Eligible articles were identified by a search of MEDLINE and ClinicalTrial.gov database concerning the period 2000/01/01-2021/05/01. Results: Arthralgia was reported in 13.2 to 68.7% of patients receiving AIs for early-stage breast cancer, while arthralgia induced by CDK4/6 inhibitors occurred in a much lower rate [20.5-41.2%]. Bone pain (5-28.7% vs. 2.2-17.2%), back pain (2-13.4% vs. 8-11.2%), and arthritis (3.6-33.6% vs. 0.32%) were reported less frequently in patients receiving the combination of CDK4/6 inhibitors with ET. Conclusions: CDK4/6 inhibitors might have a protective effect against joint inflammation and arthralgia occurrence. Further studies are warranted to investigate arthralgia incidence in this population.

Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: A systematic review with network meta-analysis.

Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.

Tamoxifen induced hands deformities.

INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer. In this article, we report a case of a patient who developed hand deformities following long-term administration of tamoxifen. CASE REPORT: A 57-year-old woman, followed for invasive ductal carcinoma of the left breast under tamoxifen for 7 years, presenting joint pain with deformities in her fingers. MANAGEMENT & OUTCOME: Following the appearance of the adverse effect, tamoxifen was stopped. A series of biologic and radiologic analysis were performed in order to explain the appearance of this event. A substitution treatment was discussed and a rheumatologist's opinion was requested. DISCUSSION: Tamoxifen appears to be associated with the development of inflammatory osteoarthritis resembling rheumatoid arthritis. Possible mechanisms of such an effect are discussed.

[Impact of adapted physical activity on joint pain induced under adjuvant hormone therapy for breast cancer: A review of the literature]. / Impact de l'activité physique adaptée sur les douleurs articulaires induites sous hormonothérapie adjuvante du cancer du sein : une revue de la littérature.

Hormone therapy provides an excellent survival rate after cancer but has many side effects, including joint pain in one out of two women. This leads about 13 % of women to stop their treatment within the first 6 months, impacting on its effectiveness, survival and the risk of recurrence. In order to better manage pain and quality of life, physical activity is highly recommended. In this context, the present review proposes a state of the art on the effects of adapted physical activity, based on the works referenced in PubMed. These studies show that physical activity has proved its worth in the primary prevention of cancer and is being evaluated in secondary prevention, particularly in the reduction of adverse effects. Overall, there is a reduction in joint pain, an improvement in quality of life and fatigue. Physical activity also plays a role in tertiary prevention. Paradoxically, oncologists and educators often note a reduction in the practice of physical activity due to fear of the onset of pain. It seems necessary to reinforce communication with patients and health professionals and to recommend the practice of physical activity in an appropriate setting.

Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab.

OBJECTIVES: In some patients with RA, joint pain is more severe than expected based on the amount of joint swelling [referred to as disproportionate articular pain (DP)]. We assessed DP prevalence and the effects of sarilumab, an IL-6 inhibitor, on DP. METHODS: Data from RA patients treated with placebo or 200 mg sarilumab in the phase 3 randomized controlled trials (RCTs) MOBILITY and TARGET, adalimumab 40 mg or sarilumab 200 mg in the phase 3 RCT MONARCH and sarilumab 200 mg in open-label extensions (OLEs) were used. DP was defined as an excess tender 28-joint count (TJC28) over swollen 28-joint count (SJC28) of ≥7 (TJC28 - SJC28 ≥ 7). Treatment response and disease activity were determined for patients with and without DP. RESULTS: Of 1531 sarilumab 200 mg patients from RCTs, 353 (23%) had baseline DP. On average, patients with DP had higher 28-joint DAS using CRP (DAS28-CRP) and pain scores than patients without DP, whereas CRP levels were similar. After 12 and 24 weeks, patients with baseline DP treated with sarilumab were more likely to be DP-free than those treated with placebo or adalimumab. In RCTs, more sarilumab-treated patients achieved low disease activity vs comparators, regardless of baseline DP status. In OLEs, patients were more likely to lose rather than gain DP status. CONCLUSION: About one-quarter of patients with RA experienced DP, which responded well to sarilumab. These data support the concept that other mechanisms (potentially mediated via IL-6) in addition to inflammation may contribute to DP in RA. TRIAL REGISTRATIONS: NCT01061736, NCT02332590, NCT01709578, NCT01146652.

Musculoskeletal immune-related adverse events in 927 patients treated with immune checkpoint inhibitors for solid cancer.

OBJECTIVE: The prevalence of the musculoskeletal immune-related adverse events (irAEs) is probably underestimated, as most studies report only severe side effects. Our aim was to describe and characterize all musculoskeletal irAEs in a large cohort of patients treated with immune checkpoint inhibitors (ICI). METHODS: We conducted a retrospective study among patients who received ICI from 07/27/2014 to 05/08/2020 at the medical oncology department of the Institut Paoli-Calmettes, Marseille, France. All medical files were systemically reviewed by a rheumatologist who collected clinical features, time of occurrence, treatment regimen, irAEs management, course and outcomes. We also assessed tumor response 3 months after introduction of ICI, according to severity and treatments used to manage musculoskeletal irAEs. RESULTS: Among 927 patients treated with ICI for a solid tumor, 118 patients (12.7%) presented a musculoskeletal irAE. Their median age was 66.5, 61% were male, and they mainly had a lung (57.6%) or urological cancer (27.1%). The most frequently involved ICI was an anti PD-1. Arthralgias and myalgias were the most frequent musculoskeletal irAEs (9.8%) and inflammatory rheumatic features were reported in 36 patients (3.9%) with elevated acute phase reactants and negative immunological markers. The median time of onset was 2 months (IC 95% 1.8; 2.7). Tumor response at 3 months did not differ according to musculoskeletal irAE severity, type of manifestation (arthralgias/myalgias versus inflammatory rheumatic features), pain patterns (mechanical versus inflammatory) or irAE treatments. CONCLUSION: Musculoskeletal irAEs in this large cohort of patients treated with ICI were frequent (12.7%), mostly mild and well tolerated.

Immune checkpoint inhibitor-induced arthralgia is tightly associated with improved overall survival in cancer patients.

OBJECTIVES: With the increased use of immune checkpoint inhibitors (ICIs) in cancer patients, arthralgia has been the most commonly reported musculoskeletal immune-related adverse event (irAE). We aimed to characterize arthralgia and its association with overall survival (OS). MATERIAL AND METHODS: Randomized controlled trials (RCTs) reporting on data for ICI-induced arthralgia from four online databases were comprehensively investigated. Odds ratios (ORs) with 95% CIs were calculated for arthralgia using a random-effects model meta-analysis. Individual patient data were reconstructed from RCTs assessing OS in patients with or without ICI-induced arthralgia. We also retrospectively collected data on the clinical features and outcomes of ICI-induced arthralgia in the Yokohama City University (YCU) registry. RESULTS: We analysed 14 377 patients from 24 RCTs. The OR of ICI-induced arthralgia was 1.37 (95% CI 1.20, 1.56). Of the 369 patients in the YCU registry, 50 (13.6%) developed ICI-induced arthralgia. Among them, 30 had other grade ≥2 irAEs, which was noticeably more frequent than in those without arthralgia (OR 1.92, 95% CI 1.04, 3.52). By irAE types, a significant difference was found for relative adrenal insufficiency (OR 3.88, 95% CI 1.80, 8.39). In the YCU registry, patients with (vs without) ICI-induced arthralgia had better OS (log-rank, P < 0.001). OS results were validated from RCT patients with matched cancer types, drugs, and time to arthralgia onset (hazard ratio 0.34, 95% CI 0.17, 0.65, P < 0.001). CONCLUSIONS: If arthralgia develops after ICIs, another irAE, such as relative adrenal insufficiency, may have developed. The incidence of arthralgia was associated with better OS, and the condition of patients with irAEs must be carefully evaluated to determine optimal management.

Clinical characteristics associated with falls in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide.

BACKGROUND: The phase III SPARTAN study demonstrated that apalutamide significantly improves metastasis-free survival and overall survival vs. placebo in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). However, patients receiving apalutamide experienced falls more frequently vs. those receiving placebo (15.6% vs. 9.0%). METHODS: 806 patients with nmCRPC randomized to apalutamide in SPARTAN and treated with apalutamide in addition to ongoing androgen deprivation therapy (ADT) were included in this post-hoc analysis investigating clinical variables associated with a subsequent fall. Time to a fall was assessed with Cox proportional-hazards models adjusted for baseline characteristics and time-varying factors. Statistical inference was based on final multivariable models. RESULTS: Falls were reported for 125/803 (15.6%) patients treated with apalutamide and ADT. Most falls were grade 1 or 2 and did not require hospitalization. Median time from randomization to first fall was 9.2 months (range 0.1-25.3 months). In the final multivariable model of both baseline and after-baseline covariates, baseline patient characteristics (older age, poor Eastern Cooperative Oncology Group performance status, history of neuropathy, and α-blocker use before study treatment) remained significantly associated with fall; after-baseline clinical characteristics significantly associated with time to fall were development of neuropathy, arthralgia, and weight loss before fall. CONCLUSIONS: This analysis identified risk factors for fall among nmCRPC patients treated with apalutamide. Clinical management can minimize these identified risks while enhancing patient outcomes. Preventive interventions should be considered when the identified baseline conditions and post-treatment neuropathy, arthralgia, or weight decrease are present, to reduce risk of fall. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01946204.

[A Case of Advanced Gastric Cancer Who Experienced Multiple Immune-Related Adverse Events with Nivolumab and SOX Therapy].

A 59-year-old woman who has HER2-negative advanced gastric cancer with peritoneal dissemination was treated with nivolumab plus SOX therapy as primary treatment, and hemorrhagic cystitis occurred on the 28th day after the 6 courses. On the 21st day after the 7 courses, right knee arthralgia appeared, and on the 26th day, she was admitted to the hospital due to a fever of 39℃ and anorexia. After admission, frequent diarrhea occurred and new symptoms of neck pain and left knee arthralgia appeared. Abdominal CT showed increased fatty tissue density around the sigmoid colon, and wall thickening and contrast enhancement of the mucosal surface of the bladder. Lower gastrointestinal endoscopy revealed the diffuse redness and erosions in some areas, and lymphocytic infiltration in the epithelium of the crypts was seen in biopsy from the erosions. The hemorrhagic cystitis was aseptic pyuria. Therefore, we suspected that the series of symptoms were immune-related adverse events(irAE)and started prednisolone 50 mg(1 mg/kg/day), which quickly relieved the diarrhea, cystitis and arthralgia. As a result, the patient was diagnosed as having irAE. We report a case of advanced gastric cancer who experienced multiple irAE with nivolumab plus SOX therapy, with some discussion of the literature.

Prevalence and correlates of joint pain among Chinese breast cancer survivors receiving aromatase inhibitor treatment.

BACKGROUND: Aromatase inhibitor (AI)-induced joint pain is a common toxicity of AI treatment. Although many studies have been conducted to examine the occurrence and severity of AI-induced joint pain in breast cancer survivors, none of the studies focused on the Chinese population with breast cancer. Given that the differences in cultural background and the genetic structure between Asians and Caucasians may contribute to different phenotypes of joint pain, this cross-sectional study was therefore conducted to examine the prevalence of AI-induced joint pain among Chinese breast cancer survivors receiving AI treatment and the correlates of pain. METHODS: This cross-sectional study was conducted in a tertiary hospital in China. Breast cancer survivors undergoing AI treatment were recruited to complete the following questionnaires: a self-designed baseline data form, the Nordic Musculoskeletal Questionnaire (NMQ), the Brief Pain Inventory (BPI), the 36-Item Short Form Health Survey (SF-36), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Based on the assessment results of NMQ (if the participant indicated pain in specific body parts), participants were then invited to complete other questionnaires to specifically assess the joint symptoms, including the Oxford Knee Score (OKS), the Oxford Hip Score (OHS), the Michigan Hand Outcomes Questionnaire (MHQ), and the Manchester Foot Pain Disability Questionnaire (MFPDQ). Descriptive analysis was used to analyse participants' baseline data and the prevalence of pain. Stepwise multiple regression was used to identify the correlates of pain. RESULTS: Four hundred and ten participants were analysed. According to the NMQ, 71.7% of the participants experienced joint symptoms in at least one joint, and the most frequently mentioned joint was knee (39.0%). The diagram in BPI indicated that 28.0% of the participants had the worst pain around knees. In patients with knee pain, the mean OKS score was 40.46 ± 6.19. The sub-scores of BPI for pain intensity and pain interference were 1.30 ± 1.63 and 1.24 ± 1.79, respectively. Patients' poorer physical well-being/functioning, previous use of AI treatment, presence of osteoarthritis, and receiving of physiotherapy were identified as four common correlates of greater severity of pain and pain interference (p < 0.05). CONCLUSIONS: Chinese breast cancer survivors can experience joint pain at various locations, particularly knees. In addition to increasing the use of interventions for pain alleviation, a comprehensive assessment of survivors' conditions such as physical functioning, history of AI treatment, and presence of osteoarthritis should be emphasized to identify survivors who need more attention and tailored interventions.

Systemic lupus erythematosus following human papillomavirus vaccination: A case-based review.

Systemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune diseases (AIDs) with many pathogenic factors, ranging from genetic to epigenetic to environmental. The human papillomavirus (HPV), a viral infectious agent, is a common contributor to the onset and exacerbation of SLE. HPV infections are more prevalent among SLE patients than healthy individuals, bringing about a substantial need for treatment. While HPV recombinant gene vaccines are accepted as a universal method for infection prevention, they pose a risk for adverse events such as fever, joint pain, and rashes. In rare cases, they might even trigger AIDs such as SLE, especially in patients with a personal or family history of such diseases. In this article, we provide a report of a case of SLE onset following HPV vaccination and a review of 11 similar cases. An analysis of 12 patients revealed that 7 cases of SLE developed between 3 weeks and 2 months post-vaccination. Symptoms of SLE generally manifest as fatigue, fever, joint pain, and myalgia. Two patients had lupus nephritis, 2 showed central nervous system involvement, including abnormal behavior and epileptic seizures, and 1 had intestinal pseudo-obstruction. All patients showed rapid remission with glucocorticoid and immunosuppressive therapy and remained stable during several months of follow-up.

Use of an alfa-lipoic, Methylsulfonylmethane, Boswellia serrata and Bromelain dietary supplement (OPERA®) for aromatase inhibitors-related arthralgia management (AIA): a prospective phase II trial (NCT04161833).

Aromatase Inhibitors (AIs) are recommended for the adjuvant treatment of hormone receptor positive breast cancer in both high-risk pre-menopausal and post-menopausal population; arthralgia is the main cause of discontinuation of therapy and affects up to 25% of population on AI treatment. The objective of the study was to prospectively evaluate OPERA® (GAMFARMA srl, Milan, Italy), a new dietary supplement where α-Lipoic acid, Boswellia serrata, Methylsulfonylmethane and Bromelain are combined in a single hard-gelatin capsule to be taken once a day. Fifty-three patients with arthralgia (NCI-CTCAE v4.0 grade ≥ 1) occurring during AI therapy were enrolled. All patients received OPERA® from enrollment (T0) up to sixth months (T3). Patients' AI-related arthralgia was evaluated every two months with VAS Scale, PRAI questionnaire, and CTCAE scale. Primary endpoint was the number of patients with symptom resolution (G0) at T3 if compared to T0, according to CTCAE and VAS scale. Secondary endpoints were decrease in arthralgia intensity measured with PRAI score at T3 compared to baseline, safety of OPERA® and rate of AI interruption. Treatment with OPERA® supplement was overall well tolerated; no relevant toxicities related to OPERA® intake were reported. Seven subjects (13.2%) were not included in the final analysis because of consent withdrawal. 46 participants were eligible for final analysis. According to CTCAE scale, 10 out of 46 patients reported symptoms resolution at 6-month follow-up from the time of enrollment T0 (p = 0.0009). According to VAS score, 5 patients reported complete resolution of symptoms at T3 if compared to baseline starting situation T0 (p = 0.0222). Analysis of PRAI score showed a significant reduction in arthralgia-related pain perceived (p = 0.0001). OPERA® was able to reduce the intensity of arthralgia related to AI therapy. Randomized, double-blind studies are warranted to confirm the effectiveness of this dietary supplement.

Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and meta-analysis.

OBJECTIVES: We aimed to analyze rheumatic immune-related (ir) and nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients from the available literature. METHODS: We performed a systematic review and meta-analysis of phase III randomized clinical trials (RCTs) assessing PD-(L)1-ICIs in lung cancer patients, from inception until January 12th, 2021. We extracted data of each trial to estimate odds ratio (OR) for rheumatic ir or non-irAE as classified in RCTs safety data. Sensitivity analyses (by ICI, treatment group and histology) were performed. RESULTS: Eighteen RCTs met the inclusion criteria (n=12172 subjects). The OR [95%IC] for rheumatic irAE in ICIs versus controls (either placebo or chemotherapy) was 2.20 [0.85,5.72]. Among rheumatic non-irAEs, both overall and severe (grade≥3) back pain were significantly more frequent in ICIs versus controls, 2.01 [1.09;3.73] and 2.90 [1.18;7.08], respectively. The overall frequency of arthralgia was similar between ICIs and controls; by sensitivity analysis RCTs assessing ICIs in combination with chemotherapy showed a significant association with arthralgia (1.55 [1.15;2.10]). Similarly, the frequency of myalgia was significantly lower in RCTs assessing ICIs alone versus chemotherapy (OR 0.32 [0.24;0.42]). Muscular pain was not significantly increased with ICI. CONCLUSION: Rheumatic irAEs are not increased in RCTs assessing PD-(L)1 inhibitors, not reflecting the real-life incidence, therefore likely underreported or misclassified. Back pain is significantly associated with them regardless its severity, while arthralgia only when ICIs are added on conventional chemotherapy.

Real-world burden of adverse events for apalutamide- or enzalutamide-treated non-metastatic castration-resistant prostate cancer patients in the United States.

BACKGROUND: Second-generation androgen receptor inhibitors (ARIs) have been associated with adverse events (AEs) such as fatigue, falls, fractures, and rash in non-metastatic castration-resistant prostate cancer (nmCRPC) patients as identified in clinical trials. The objectives of this study were to describe the incidence and management of AEs in patients receiving apalutamide and enzalutamide. METHODS: This retrospective chart review study was conducted in nmCRPC-treating sites in the United States. Patients starting apalutamide or enzalutamide between February 1, 2018 and December 31, 2018 were included and any AEs they experienced were recorded. AEs, including those considered to be of special interest as defined in the pivotal clinical trials of the second-generation ARIs, were analyzed and grouped retrospectively in this study. Detailed chart data (patient demographics, clinical characteristics, treatment history, type of AE, outcomes, and resource utilization) were then collected for a randomly selected subset among patients with ≥1 AE to characterize AEs and their management. Descriptive results were summarized. RESULTS: Forty-three sites participated in the study. A total of 699 patients were included, of whom 525 (75.1%) experienced ≥1 AE. The most common AEs were fatigue/asthenia (34.3%), hot flush (13.9%), and arthralgia (13.6%). In the subset of 250 patients randomly selected from those who experienced ≥1 AE, patients were primarily White (72.0%), the mean age was 71 years, 86.0% had an Eastern Cooperative Oncology Group score of 0-1 at nmCRPC diagnosis, and the average prostate specific antigen (PSA) value at diagnosis was 23.2 ng/mL. PSA-doubling time < 10 months was chosen as reason to initiate treatment in 40% of patients. The median duration of follow-up was 1.1 years, with 14.4% of patients progressing to metastasis by end of study period. Grade 3-4 and Grade 5 AEs occurred in 14.4 and 0.4% of patients, respectively. Actions taken to manage AEs included AE-directed treatment (38.0%), ARI discontinuation (10.4%), dose reduction (7.6%), and AE-related hospitalization (4.8%). CONCLUSIONS: This study highlights the burden of AEs among nmCRPC patients treated with apalutamide or enzalutamide, providing a relevant real-world benchmark as clinical trial evidence and the treatment landcape for nmCRPC continues to evolve.