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.

Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial.

BACKGROUND: Rheumatoid arthritis is the most common autoimmune disease worldwide and requires long-term treatment to suppress inflammation. Currently, treatment is started when arthritis is clinically apparent. We aimed to evaluate whether earlier intervention, in the preceding phase of arthralgia and subclinical joint inflammation, could prevent the development of clinical arthritis or reduce the disease burden. METHODS: We conducted a randomised, double-blind, placebo-controlled, proof-of-concept-trial at the Leiden University Medical Centre, Leiden, Netherlands. Adults aged 18 years or older with arthralgia clinically suspected of progressing to rheumatoid arthritis and MRI-detected subclinical joint inflammation were eligible for enrolment across 13 rheumatology outpatient clinics in the southwest region of the Netherlands and randomly assigned (1:1) to a single intramuscular glucocorticoid injection (120 mg) and a 1-year course of oral methotrexate (up to 25 mg/week), or placebo (single injection and tablets for 1 year). Participants and investigators were masked to group assignment. Follow-up continued for 1 year after the end of the 1-year treatment period. The primary endpoint was development of clinical arthritis (fulfilling the 2010 rheumatoid arthritis classification criteria or involving two or more joints) that persisted for at least 2 weeks. Patient-reported physical functioning, symptoms, and work productivity were secondary endpoints, which were measured every 4 months. Additionally, the course of MRI-detected inflammation was studied. All participants entered the intention-to-treat analysis. This trial is registered with EudraCT, 2014-004472-35, and the Netherlands Trial Register, NTR4853-trial-NL4599. FINDINGS: Between April 16, 2015, and Sept 11, 2019, 901 patients were assessed for eligibility and 236 were enrolled and randomly assigned to active treatment (n=119) or placebo (n=117). At 2 years, the frequency of the primary endpoint was similar between the groups (23 [19%] of 119 participants in the treatment group vs 21 [18%] of 117 in the placebo group; hazard ratio 0·81, 95% CI 0·45 to 1·48). Physical functioning improved more in the treatment group during the first 4 months and remained better than in the placebo group (mean between-group difference in Health Assessment Questionnaire disability index over 2 years: -0·09, 95% CI -0·16 to -0·03; p=0·0042). Similarly, pain (on scale 0-100, mean between-group difference: -8, 95% CI -12 to -4; p<0·0001), morning stiffness of joints (-12, -16 to -8; p<0·0001), presenteeism (-8%, -13 to -3; p=0·0007), and MRI-detected joint inflammation (-1·4 points, -2·0 to -0·9; p<0·0001) showed sustained improvement in the treatment group compared with the placebo group. The number of serious adverse events was equal in both groups; adverse events were consistent with the known safety profile for methotrexate. INTERPRETATION: Methotrexate, the cornerstone treatment of rheumatoid arthritis, initiated at the pre-arthritis stage of symptoms and subclinical inflammation, did not prevent the development of clinical arthritis, but modified the disease course as shown by sustained improvement in MRI-detected inflammation, related symptoms, and impairments compared with placebo. FUNDING: Dutch Research Council (NWO; Dutch Arthritis Society).

Effectiveness, safety, and economic evaluation of adjuvant moxibustion therapy for aromatase inhibitor-induced arthralgia of postmenopausal breast cancer stage I to III patients: Study protocol for a prospective, randomized, assessor-blind, usual-care controlled, parallel-group, pilot clinical trial.

INTRODUCTION: This study is a prospective, assessor-blinded, parallel-group, randomized controlled pilot trial to explore the effectiveness of 12-week adjuvant moxibustion therapy for arthralgia in menopausal females at stage I to III breast cancer on aromatase inhibitor (AI) administration, compared with those receiving usual care. METHODS/DESIGN: Forty-six menopausal female patients with breast cancer who completed cancer therapy will be randomly allocated to either adjuvant moxibustion or usual care groups with a 1:1 allocation ratio. The intervention group will undergo 24 sessions of adjuvant moxibustion therapy with usual care for 12 weeks, whereas the control group will receive only usual care during the same period. The usual care consists of acetaminophen administration on demand and self-directed exercise education to manage AI-related joint pain. The primary outcome is the mean change of the worst pain level according to the Brief Pain Inventory-Short Form between the initial visit and the endpoint. The mean changes in depression, fatigue, and quality of life will also be compared between groups. Safety and pharmacoeconomic evaluations will also be included. DISCUSSION: Continuous variables will be compared by an independent t test or Wilcoxon rank-sum test between the adjuvant moxibustion and usual care groups. Adverse events will be analyzed using the chi-square or Fisher exact test. The statistical analysis will be performed by a 2-tailed test at a significance level of .05.

Randomized clinical trial comparing efficacy and safety of brand versus generic alendronate (Bonmax®) for osteoporosis treatment.

INTRODUCTION: Although the same efficacy and tolerability are anticipated due to both drugs containing the same active ingredients, comparative studies between brand and generic alendronate are limited. Accordingly, the objective of this study was to compare efficacy and safety between brand alendronate and a recently introduced generic alendronate drug. METHODS: A total of 140 postmenopausal women or men aged older than 50 years who met the indications for osteoporosis treatment were randomized to receive either generic (Bonmax®) or brand alendronate (Fosamax®) 70 mg/week over a 12-month period during the May 2014 to June 2015 study period. Endpoints included bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck; percentage of patients with predefined levels of change in total hip and lumbar spine BMD at 12 months; and, changes in biochemical bone markers at 3, 6, and 12 months. Tolerability was evaluated by patient self-reporting of adverse experiences. RESULTS: At 12 months post-treatment, BMD significantly increased at all sites in both groups. There were no differences in BMD percentage changes or the number of patients with stable or increased BMD after 1 year between groups. No significant differences in the amount of biochemical bone marker reduction or incidence of adverse events were observed between groups. CONCLUSIONS: Generic and brand alendronate produced similar gains in BMD and reduction in bone turnover markers. Both medicadoitions were also equally well-tolerated. Based on these findings, generic alendronate (Bonmax®) is a viable alternative to the original brand of alendronate. TRIAL REGISTRATION: ClinicalTrials.gov NCT02371252.

Development and Content Validity of the Statin Experience Assessment Questionnaire (SEAQ)©.

INTRODUCTION: The National Lipid Association Statin Intolerance (SI) Panel recognized the need for better understanding of the patient SI experience. OBJECTIVE: The objective of this research was to develop a patient-reported outcome (PRO) questionnaire to assess a patient's experience with SI. METHODS: Questionnaire development was informed via a series of research activities: literature review, concept elicitation, item generation, and content evaluation. Following the literature review and concept elicitation, a draft questionnaire was constructed and subsequently modified based on feedback from therapeutic area experts and patients via cognitive debriefing interviews. RESULTS: Muscle-related symptoms were the most commonly reported symptoms associated with SI in the literature review (35 of 41 articles reviewed [85%]) and in semi-structured interviews with experts (n = 5 [100%]) and patients (n = 17 of 20 [85.0%]). Physical and other impacts of SI symptoms on daily activities were also frequently reported. A 17-item draft questionnaire was created, and cognitive debriefing with experts (n = 5) and patients (n = 15) was conducted. Overall, the items, response options, and instructions were comprehensible and positively reviewed; minor changes resulted in the 15-item Statin Experience Assessment Questionnaire (SEAQ)©. Using a 30-day recall period, the SEAQ© assesses the severity and impact of six SI symptoms (muscle ache, muscle pain, muscle cramps, muscle weakness, tiredness, and joint pain) on an 11-point numeric scale. Statin discontinuation and likelihood of discontinuation due to symptoms are assessed and scored on a yes/no and five-point verbal response scale, respectively. CONCLUSION: The SEAQ

Adaptation of an Evidence-Based Arthritis Program for Breast Cancer Survivors on Aromatase Inhibitor Therapy Who Experience Joint Pain.

Adding aromatase inhibitors (AIs) to adjuvant treatment of postmenopausal women with hormone-receptor-positive breast cancer significantly reduces cancer recurrence. A common side effect of AIs is noninflammatory joint pain and stiffness (arthralgia) similar to arthritis symptoms. An evidence-based walking program developed by the Arthritis Foundation - Walk With Ease (WWE) - reduces arthritis-related joint symptoms. We hypothesized that WWE may also reduce AI-associated arthralgia. However, the potential for different barriers and facilitators to physical activity for these 2 patient populations suggested a need to adapt WWE before testing it with breast cancer survivors. We conducted qualitative research with 46 breast cancer survivors to explore program modification and inform the development of materials for an adapted program (Walk With Ease-Breast Cancer). Our process parallels the National Cancer Institute's Research-Tested Intervention Programs (RTIPs) guidelines for adapting evidence-based programs for cancer populations. Findings resulted in a customized 8-page brochure to supplement existing WWE materials.

A modified filgrastim regimen does not reduce pain burden compared to pegfilgrastim in women receiving chemotherapy for non-metastatic breast cancer.

PURPOSE: The short half-life of filgrastim allows for modification in the dose or duration of prophylaxis to limit inconvenience, adverse effects, and cost. The objectives of this study were to characterize and compare pain and neutropenic events between filgrastim and pegfilgrastim. METHODS: A prospective, observational study was performed. Eligible patients had non-metastatic breast cancer and were to receive adjuvant or neo-adjuvant chemotherapy with prophylaxis for febrile neutropenia. The prophylaxis used was a fixed-dose regimen of filgrastim 300 µg subcutaneously once daily for 7 days or pegfilgrastim 6 mg subcutaneously for 1 day. Participants completed a pain diary once a day for 14 days commencing the evening of the patient's first chemotherapy. Telephone interviews occurred at two instances within 2 weeks after their first treatment. The primary endpoints of this study were the difference in pain and incidences of neutropenia. Muscle pain, pain burden, and potential risk factors for pain were also explored. RESULTS: A total of 142 women were enrolled, 94 with pegfilgrastim and 48 with filgrastim. Filgrastim was associated with worse joint and muscle pain compared to pegfilgrastim. Joint pain was present in 38 and 26 % of diary entries for filgrastim and pegfilgrastim, respectively (p = 0.009). The mean AUC for joint pain score across 14 days, normalized to 100, were 6.0 for pegfilgrastim and 8.6 for filgrastim in patients receiving non-docetaxel chemotherapy and 14.6 for pegfilgrastim and 21.5 for filgrastim in patients receiving docetaxel-based chemotherapy (p = 0.037). Muscle pain patterns and frequencies were similar to joint pain. There were no statistical differences in febrile neutropenia and neutropenic events. CONCLUSIONS: Both filgrastim and pegfilgrastim caused significant pain burden. A fixed-dose regimen of filgrastim may be effective, but offers no advantage to minimize muscle or joint pain and, in fact, appears to cause greater and more frequent pain.

Hormonal prevention of breast cancer.

Breast cancer prevention can be provided by using SERMs or aromatase inhibitors depending on the ovarian status, with a global risk reduction of 50 to 60%. Prophylactic annexectomy offered to reduce ovarian risk in BRCA mutation carriers also lowers breast cancer risk by 50%. Main side effects include deep vein thrombosis for SERMs, hot flushes and joint pain (although less frequently than initially suspected) with aromatase inhibitors. Other strategies based on progesterone, insulin or prolactin signaling modulation may be offered in the future. Criteria for candidate selection remain to be established.

Patients' self-assessment versus investigators' evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15).

BACKGROUND: Toxicity, which is a key parameter in the evaluation of cancer treatments, can be underestimated by clinicians. We investigated differences between patients and physicians in reporting adverse events of androgen deprivation therapy (ADT) with or without docetaxel in a multicentre phase III trial in non-castrate metastatic prostate cancer. METHODS: The 385 patients included were invited to complete a 26-symptom questionnaire 3 and 6 months after the start of treatment, among which eighteen symptoms were also assessed by physicians, reported in medical records and graded using the Common Toxicity Criteria of the National Cancer Institute. Positive and negative agreements as well as Kappa concordance coefficients were computed. FINDINGS: Data were available for 220 and 165 patients at 3 and 6 months respectively. Physicians systematically under-reported patients' symptoms. Positive agreement rates (at respectively 3 and 6 months) for the five most commonly reported symptoms were: 61.0% and 64.3% hot flushes, 50.0% and 43.6% fatigue, 29.4% and 31.1% sexual dysfunction, 24.4% and 14.4% weigh gain/loss, 16.7% and 19.3% for joint/muscle pain. For symptoms most frequently reported as disturbing or very disturbing by patients, the clinicians' failure to report them ranged from 50.8% (hot flushes) to 89.5% (joint/muscle pain) at 3 months, and from 48.2% (hot flushes) to 88.4% (joint/muscle pain) at 6 months. INTERPRETATION: Physicians often failed to report treatment-related symptoms, even the most common and disturbing ones. Patients' self-evaluation of toxicity should be used in clinical trials to improve the process of drug assessment in oncology. FUNDING: French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, Astra-Zeneca, and Amgen.

Incidence and management of arthralgias in breast cancer patients treated with aromatase inhibitors in an outpatient oncology clinic.

PURPOSE: Aromatase inhibitors (AIs) are routinely used as first-line adjuvant treatment of breast cancer in postmenopausal women with hormone receptor positive tumors. The current recommended length of treatment with an AI is 5 years. Arthralgias have been frequently cited as the primary reason for discontinuation of AI therapy. Various treatment strategies are proposed in literature, but a standardized treatment algorithm has not been established. The initial purpose of this study was to describe the incidence and management of AI-induced arthralgias in patients treated at Kellogg Cancer Center (KCC). Further evaluation led to the development and the implementation of a treatment algorithm and electronic medical record (EMR) documentation tools. METHODS: The retrospective chart review included 206 adult patients with hormone receptor positive breast cancer who were receiving adjuvant therapy with an AI. A multidisciplinary treatment team consisting of pharmacists, collaborative practice nurses, and physicians met to develop a standardized treatment algorithm and corresponding EMR documentation tool. The treatment algorithm and documentation tool were developed after the study to better monitor and proactively treat patients with AI-induced arthralgias. RESULTS/ CONCLUSIONS: The overall incidence of arthralgias at KCC was 48% (n = 98/206). Of these patients, 32% were documented as having arthralgias within the first 6 months of therapy initiation. Patients who reported AI-induced arthralgias were younger than patients who did not report AI-induced arthralgias (61 vs. 65 years, p = 0.002). There was no statistical difference in the incidence of arthralgias in patients with a history of chemotherapy (including taxane therapy) compared to those who did not receive chemotherapy (p = 0.352). Of patients presenting with AI-induced arthralgias, 41% did not have physician-managed treatment documented in the EMR. A standardized treatment algorithm and electronic chart documentation tools were then developed by the multidisciplinary team.