"To prescribe or not to prescribe, that is the question": Perspectives on opioid prescribing for chronic, cancer-related pain from clinicians who treat pain in survivorship.

BACKGROUND: Opioid pain management in cancer survivorship is a complex and understudied topic. METHODS: The authors conducted in-depth, qualitative interviews to understand clinician approaches to opioid pain management in chronic cancer pain and to generate ideas for improvement. They used a rigorous, inductive, qualitative, descriptive approach to examine clinician (n = 20) perspectives about opioid pain management in survivorship, including oncologists (n = 5), palliative care clinicians (n = 8), primary care clinicians (n = 5), and pain management specialists (n = 2). RESULTS: The findings indicated that no consistent medical home exists for chronic pain management in cancer survivors and that there are fundamental differences in how each subspecialty approaches chronic pain management in survivorship (e.g., "Do we think of this as noncancer pain or cancer pain?… This is in this limbo zone-this gray zone-because it's cancer-related pain, right?"). Simultaneously, clinicians are influenced by their peers' perceptions of their opioid prescribing decisions, sparking intraprofessional tension when disagreement occurs. In these instances, clinicians described overthinking and doubting their clinical decision-making as well as a sense of judgment, pressure, and/or shame. Finally, clinicians acknowledged a fear of consequences for opioid prescribing decisions. Specifically, participants cited conflict with patients, sometimes escalating to aggression and threats of violence, as well as potential disciplinary actions and/or legal consequences. CONCLUSIONS: Participants suggested that opportunities to improve chronic cancer pain care include developing clear, systematic guidance for chronic cancer pain management, facilitating clinician communication and consultation, creating tailored survivorship care plans in partnership with patients, and developing accessible, evidence-based, complementary pain treatments.

Buprenorphine dispensing before and after the April 2021 X-Waiver exemptions: An interrupted time series analysis.

BACKGROUND: Until the end of 2022, a special registration, known as the X-waiver, was required to prescribe buprenorphine in the US. Before its removal, US federal regulations trialed an X-waiver exemption, initiated on April 28, 2021, which permitted buprenorphine prescribing for up to 30 patients without additional training. We aimed to understand if these regulatory changes impacted buprenorphine dispensing. METHODS: We conducted an interrupted time series analysis to understand changes in buprenorphine dispensing during the 26 weeks after the X-waiver exemption compared to the expected baseline trend established in the 26 weeks before using the IQVIA Longitudinal Prescription claims database. The primary outcome was number of new buprenorphine prescribers nationwide (defined as no prior buprenorphine prescription dispensed in the last 26 weeks). Segmented regression estimated relative changes in buprenorphine dispensing at 1, 13, and 26 weeks post-X-waiver change. RESULTS: A total of 15,517,525 prescriptions filled for 1,328,172 patients (43.4 % female) ordered by 62,312 providers were included for analysis. At 26 weeks post-X-waiver change, there was no change in the number of new prescribers compared to the expected baseline trend (-2.7 % [95 % CI:-8.3,2.9]). The number of new (15.2 % [4.6,25.8]) and existing (1.7 % [0.9,2.4]) patients and patients per prescriber (4.3 % [3,5.6]) increased. Buprenorphine prescriptions reimbursed by Medicaid increased (7.5 % [6.6,8.4]) while commercial fills decreased (-3.4 % [-5.3,-1.5]). CONCLUSIONS: The number of new prescribers did not increase six months post-X-waiver exemption while new patients continued to enter treatment at higher-than-expected rates. These findings suggest that additional interventions beyond the recent X-waiver removal may be needed to increase access to buprenorphine.

Stakeholder-Driven Intervention Development for Dialysis Trials Using a Design Sprint Methodology.

Rationale & Objective: Stigma contributes to ineffective treatment for pain among individuals with kidney failure on dialysis, particularly with buprenorphine pain treatment. To address stigma, we adapted a Design Sprint, an industry-developed structured exercise where an interdisciplinary group works over 5 days to clarify the problem, identify and choose a solution, and build and test a prototype. Study Design: Adapted Design Sprint which clarified the problem to be solved, proposed solutions, and created a blueprint for the selected solution. Settings & Participants: Five individuals with pain and kidney disease receiving dialysis, 5 physicians (nephrology, palliative care, and addiction medicine) and 4 large dialysis organization leaders recruited for specific expertise or experience. Conducted through online platform (Zoom) and virtual white board (Miro board). Analytical Approach: Descriptions of the Design Sprint adaptations and processes. Results: To facilitate patient comfort, a patient-only phase included four 90-minute sessions over 2-weeks, during which patient participants used a mapping process to define the critical problem and sketch out solutions. In a physician-only phase, consisting of two 120-minute sessions, participants accomplished the same tasks. During a combined phase of two 120-minute sessions, patients, physicians, and large dialysis organization representatives vetted and developed solutions from earlier phases, leading to an intervention blueprint. Videoconferencing technology allowed for geographically diverse representation and facilitated participation from patients experiencing medical illness. The electronic whiteboard permitted interactive written contributions and voting on priorities instead of only verbal discussion, which may privilege physician participants. A skilled qualitative researcher facilitated the sessions. Limitations: Challenges included the time commitment of the sessions, absences owing to illness or emergencies, and technical difficulties. Conclusions: An adapted Design Sprint is a novel method of efficiently and rapidly incorporating multiple stakeholders to develop solutions for clinical challenges in kidney disease. Plain Language Summary: Stigma contributes to ineffective treatment for pain among individuals with kidney failure on dialysis, particularly when using buprenorphine, an opioid pain medicine with a lower risk of sedation used to treat addiction. To develop a stigma intervention, we adapted a Design Sprint, an industry-developed structured exercise where an interdisciplinary group works over 5 days to clarify the problem, identify and choose a solution, and build and test a prototype. We conducted 3 sprints with (1) patients alone, (2) physicians alone, and (3) combined patients, physicians, and dialysis organization representatives. This paper describes the adaptations and products of sprints as a method for gathering diverse stakeholder voices to create an intervention blueprint efficiently and rapidly.

Impact of COVID-19-related regulatory changes on nationwide access to buprenorphine: An interrupted time series design.

Background: The impact of COVID-19-related healthcare changes on access to buprenorphine (BUP) nationwide in the US is unknown. Methods: We conducted an interrupted time series with the IQVIA LRx database. The study timeline included BUP prescriptions from 52 weeks before (2/23/19-2/21/20) to 52 weeks after (4/4/20-4/2/21) the initial pandemic period (2/22/20-4/3/20). Segmented regression estimated relative changes in total milligrams (MG) of BUP available per week nationwide at 1, 26, and 52 weeks post-initial-pandemic. We evaluated treatment disruptions in previously stable patients, defined as ≥6 months of BUP prescriptions. Results: A total of 31 617 849 prescriptions were included. Total MG BUP dispensed increased at 1 and 26 weeks and then returned to baseline trends at 52 weeks post-initial pandemic period (4.1% [95% CI: 3.7,4.5], 2.1% [1.5,2.6], 0.1% [-0.6,0.9]). Stably-treated patients saw a decrease in 7-, 14-, and 28-day treatment disruptions at 52 weeks post-initial-pandemic period (-21.6% [-25.6,-17.7]; -10.8% [-16.3,-5.3]; -27.3% [-33.0,-21.6]). Men retained an increase in MG BUP compared to women at 52 weeks (0.7% [0.01,1.4] versus -0.6% [-1.5,0.2]). Younger age groups (18-29 years and 30-39 years) had a decrease in MG BUP at 52 weeks compared to expected baseline trend (-16.6 [-24.2, -9.0]; -1.6 [-3.0, -0.1). Patients with Medicaid demonstrated an increase in MG BUP at 52 weeks (8.3% [6.3,10.3]). MG BUP prescribed by APP prescribing increased by over 140 000 mg per week prior to the pandemic and continued to increase. Conclusions: Regulatory changes around buprenorphine prescribing facilitated patient access to buprenorphine during the pandemic.

The benefits and consequences of the COVID-19 pandemic for patients diagnosed with cancer and their family caregivers.

BACKGROUND: The objectives of this study were to examine benefits and consequences of the COVID-19 pandemic for patients diagnosed with cancer and their family caregivers. METHODS: A 23-item questionnaire assessing COVID-19-related issues, the Patient Health Questionnaire-2, Generalized Anxiety Disorder-2, Pittsburgh Sleep Quality Index, and the Perceived Stress Scale (PSS)-4 were administered to patients diagnosed with cancer and their family caregivers. RESULTS: Of the 161 patients and 78 caregivers who participated, 38.1% and 32.8 were male, 95% and 84.6% Caucasian, and the mean age was 66 and 64.6 years, respectively. A total of 16.5% and 15.2% reported depressive symptoms, 18.4% and 19% reported anxiety; 35.5% and 26.6% reported poor sleep quality, and 66% and 63.3% scored one standard deviation above the norms for the PSS, respectively. Predictors of poorer patient- and caregiver-reported outcomes included greater loneliness, worry about self or family being infected by the COVID-19, and worsening relationships with family. The fear of COVID-19 led to 20.8% of patients and 24.4% of family caregivers cancelling medical appointments, procedures, and treatments. A total of 52.5% of patients and 53.2% caregivers reported that the pandemic led to benefit finding but these changes were not associated with any of the measured patient- or caregiver-related outcomes. CONCLUSIONS: Psychological functioning for patients and caregivers was similar to that of pre-pandemic levels, however the decrease in health care utilization secondary to fear of COVID-19 was notable. While there were many negative effects of the pandemic, the majority of patients and caregivers reported some benefit to the pandemic.

Regulation of cyclic adenosine 3',5'-monophosphate response element binding protein (CREB) expression by Sp1 in the mammalian testis.

In the mammalian testis, the binding of FSH to Sertoli cells activates the cAMP-dependent protein kinase A signaling pathway, resulting in the phosphorylation of the cAMP response element binding protein (CREB). Previous studies have also shown that CREB gene expression is activated by cAMP in Sertoli cells and that 2 cAMP response elements (CREs) that bind CREB and a neighboring Sp1 binding site are required for basal and cAMP-inducible CREB promoter activity. In contrast, CREB expression has been less well characterized in testis germ cells. We demonstrated that CREB and Sp1 are expressed in early germ cells only through the midpachytene stage of spermatogenesis. Furthermore, CREB promoter activity was induced over 70-fold by transient overexpression of Sp1 in SL2 cells, suggesting that Sp1 is an important regulator of CREB expression. Further studies of the CREB promoter revealed an additional regulatory element in the -130 region between the Sp1 and CREB transcription factor binding sites that is necessary for full promoter activity. Proteins expressed in Sertoli cells and germ cells bind specifically to the newly identified regulatory region. These studies suggest that proteins binding to Sp1 motifs and the -130 region are required to activate the CREB promoter.