Perspective on Intradiscal Therapies for Lumbar Discogenic Pain: State of the Science, Knowledge Gaps, and Imperatives for Clinical Adoption.

Specific clinical diagnostic criteria have established a consensus for defining patients with lumbar discogenic pain. However, if conservative medical management fails, these patients have few treatment options short of surgery involving discectomy often coupled with fusion or arthroplasty. There is a rapidly-emerging research effort to fill this treatment gap with intradiscal therapies that can be delivered minimally-invasively via fluoroscopically guided injection without altering the normal anatomy of the affected vertebral motion segment. Viable candidate products to date have included mesenchymal stromal cells, platelet-rich plasma, nucleus pulposus structural allograft, and other cell-based compositions. The objective of these products is to repair, supplement, and restore the damaged intervertebral disc as well as retard further degeneration. In doing so, the intervention is meant to eliminate the source of discogenic pain and avoid surgery. Methodologically rigorous studies are rare, however, and based on the best clinical evidence, the safety as well as the magnitude and duration of clinical efficacy remain difficult to estimate. Further, we summarize the US Food and Drug Administration's (FDA) guidance regarding the interpretation of the minimal manipulation and homologous use criteria, which is central to designating these products as a tissue or as a drug/device/biologic. We also provide perspectives on the core evidence and knowledge gaps associated with intradiscal therapies, propose imperatives for evaluating effectiveness of these treatments and highlight several new technologies on the horizon.

Improving food insecurity screening across a health system throughout the COVID-19 pandemic.

BACKGROUND: Food insecurity has direct and indirect negative outcomes on the physical and mental health of children, with impacts throughout adult life. Rates of food insecurity have increased dramatically since the start of the COVID-19 pandemic. The American Academy of Pediatrics recommends paediatricians screen and intervene to address food insecurity. We aimed to increase the percentage of patient encounters with food insecurity screening completion at the paediatric medical home from 0% to 85% by July 2020 with extension to the paediatric emergency department (ED) and paediatric specialty clinic in the following year. METHODS: This multicentre project occurred in three sites within our health system: a teaching safety-net, paediatric medical home; a paediatric ED; and five divisions within paediatric specialty medical clinics. A screening tool was created using the validated Hunger Vital Sign Questionnaire. A standard screening, documentation and referral process was developed. The Model for Improvement was used testing changes via Plan-Do-Study-Act cycles. RESULTS: The percentage of households screened for food insecurity increased from a median of 0% to 30% for all sites combined. There was significant variability in screening with the ED screening a median of 24% and the medical home screening 80% by the end of the study period. A total of 9842 households (20.9%) screened were food insecure. During the study period, 895 families with 3925 household members received 69 791 pounds of food from our primary community resource using our clinic's food prescription. Of these families, 44% (398) also qualified for the US Department of Agriculture programme ensuring ongoing food distribution up to twice a month. DISCUSSION: Using quality improvement methodology to address a critical community need, we implemented food insecurity screening across a hospital system including multiple sites and specialties and provided critical resources to households in need.

Gastroscopy for dyspepsia: Understanding primary care and gastroenterologist mental models of practice: A cognitive task analysis approach.

Background: Gastroscopy to investigate dyspepsia without alarm symptoms rarely results in clinically actionable findings or sustained health-related quality-of-life improvements among patients aged 18-60 years and is, therefore, not recommended. Despite this, referrals for and performance of gastroscopy among this patient population remain high. The purpose of this study was to understand family physicians' and gastroenterologists' mental models of dyspepsia and the drivers behind referring or performing gastroscopy. Methods: Cognitive task analysis routine critical decision method interviews with family physicians (n = 8) and gastroenterologists (n = 4). Results: Family physicians and gastroenterologists hold rich mental models of dyspepsia that rely on sensemaking; however, gaps in information continuity affect their ability to plan and coordinate patient care. Drivers behind decisions to refer or perform gastroscopy were: eliminating risk for serious pathology, providing reassurance, perceived preference by patients to receive information and reassurance from gastroenterologists, maintaining relationships with patients, and saving costs to the health system. Conclusions: Family physicians refer for dyspepsia when they are seeking support from gastroenterologists, they believe that alternative factors may be impacting the patient's health or view it as a cost-saving measure. Likewise, gastroenterologists perform gastroscopy for dyspepsia when they perceive it as a cost-saving measure, they want to support their primary care colleagues and provide their colleagues and patients with reassurance. An improved degree of communication between speciality and primary care could allow for continuity in the transfer of information about patients and reduce referrals for dyspepsia.

Patient-Reported Satisfaction with Using a Rechargeable 10 kHz Spinal Cord Stimulation Device.

Introduction: Chronic pain is a common clinical condition and is frequently treated with a variety of medications, but pharmacotherapy is oftentimes not the optimal long-term treatment option. Safe and effective long-term pain relief for trunk and limb pain is available using high-frequency spinal cord stimulation at 10 kHz (10 kHz SCS), which is delivered using a rechargeable implantable pulse generator (IPG). Although rechargeable devices have been shown to reduce patient risk and overall cost by eliminating the need for periodic surgeries to replace depleted non-rechargeable IPGs, there is little published evidence that rechargeable technology is practical and convenient for patients, especially in the context of 10 kHz SCS. Objective: This analysis of real-world patients implanted with 10 kHz SCS devices was undertaken using patient data from an industry-maintained database to investigate whether there was a substantial burden associated with rechargeable SCS and the degree of patient satisfaction or dissatisfaction with 10 kHz SCS. Results: This study included 10,391 men and women who were implanted with 10 kHz SCS devices to treat chronic pain of the trunk and/or limbs. They received stimulation for a median of 361 days (180-1550 days), and 65.48% had previous spine surgery. In this patient sample, most patients were satisfied with the efficacy of 10 kHz SCS, including 77% who would repeat the procedure and 71% who would recommend it to other patients with similar pain. In regards to IPG recharging, 70% were satisfied or very satisfied and 19% were neutral, and a majority of patients recharged their device daily for 30 to 60 minutes. Conclusion: These results indicate most patients do not find IPG recharging inconvenient or burdensome. In addition, IPG recharging is not a barrier to the majority of patients benefitting from 10 kHz SCS for long-term pain relief.

High-frequency (10 kHz) spinal cord stimulation (SCS) as a salvage therapy for failed traditional SCS: A narrative review of the available evidence.

INTRODUCTION: Traditional spinal cord stimulation (t-SCS) has been used to treat chronic pain for over 50 years. However, up to 30% of patients undergo explant, with the main indication being loss of efficacy (LoE), and few alternative treatment options exist for these patients. Strategies to mitigate LoE commonly include conversion to another type of SCS (termed 'salvage' or 'rescue'). This review summarizes the existing literature concerning the efficacy and safety of 10 kHz SCS as a salvage therapy. METHODS: We searched PubMed, the Cochrane Library, ClinicalTrials.gov, and other sources between January 2009 and April 2021. Records were retained if the authors reported clinical outcomes with a minimum of ≥ 3 months of follow-up in patients implanted with a Senza® 10 kHz SCS system in an effort to treat t-SCS LoE. RESULTS: Ten articles were eligible for inclusion, reporting 3 prospective studies and 7 retrospective reviews. In the single study that salvaged patients without a repeat trial prior to surgery, 81% of patients were responders (≥ 50% pain relief from baseline), with mean pain relief of 60%. Among repeat-trial studies, the responder rate ranged from 46% to 80%, and mean pain relief from 47% to 68%. No unanticipated therapy-related safety issues were reported among the included articles. CONCLUSION: Preliminary data suggest that chronic back and/or leg pain patients with t-SCS LoE can experience improved and durable pain relief after conversion to 10 kHz SCS. However, additional research is needed to define predictors of success and establish whether salvage without a repeat trial is a viable conversion method.

Pulse Dosing of 10-kHz Paresthesia-Independent Spinal Cord Stimulation Provides the Same Efficacy with Substantial Reduction of Device Recharge Time.

OBJECTIVE: This study was designed to assess whether using pulse dosing (PD) (regularly cycled intermittent stimulation) of high-frequency 10-kHz spinal cord stimulation (10-kHz SCS) can reduce device recharge time while maintaining efficacy in patients with chronic intractable back pain with or without leg pain. DESIGN: Prospective, multicenter, observational study. METHODS: Patients successfully using 10-kHz SCS at 100%ON (i.e., continuously with no PD) for >3 months were consecutively enrolled. After a 1-week baseline period of documenting their pain twice daily on a 0-10 numerical rating scale (NRS) using 100%ON of their "favorite" program, all subjects were reprogrammed to 14%PD for 10-14 days. If subjects preferred 14%PD to 100%ON, they were programmed to 3%PD; otherwise, they were programmed to 50%PD. Subjects used this next program for another 10-14 days. Subjects then entered a 3-month observational period during which they were requested to use but not limited to their most preferred %PD program. Toward the end of 3 months, subjects completed a 7-day NRS diary and indicated a final %PD program preference. Study endpoints included %PD preference, mean diary NRS by %PD, and daily minutes and patterns of charging. RESULTS: Of 31 subjects completing the study, 81% preferred less than 100%ON. Among the subjects, 39% preferred 3%PD, 32% preferred 14%PD, 10% preferred 50%PD, and 19% preferred 100%ON. Average daily charge durations were 8.3 ± 3.1 minutes for 3%PD, 13.9 ± 4.9 minutes for 14%PD, 26.2 ± 7.4 minutes for 50%PD, and 43.8 ± 10.9 minutes for 100%ON. Regression modeling suggested that pain relief was weighted as more than twice as influential as charging in preference for reduced %PD. CONCLUSIONS: This prospective study suggests that 10-kHz SCS therapy with PD may be successfully used in a large majority of 10-kHz SCS responders, maintaining efficacy while reducing device charging time by nearly two thirds.

Latest Evidence-Based Application for Radiofrequency Neurotomy (LEARN): Best Practice Guidelines from the American Society of Pain and Neuroscience (ASPN).

Radiofrequency neurotomy (RFN), also known as radiofrequency ablation (RFA), is a common interventional procedure used to treat pain from an innervated structure. RFN has historically been used to treat chronic facet-joint mediated pain. The use of RFN has more recently expanded beyond facet-joint mediated pain to peripherally innervated targets. In addition, there has also been the emergence of different radiofrequency modalities, including pulsed and cooled RFN. The use of RFN has been particularly important where conservative and/or surgical measures have failed to provide pain relief. With the emergence of this therapeutic option and its novel applications, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidance. The authors formed a multidisciplinary work group tasked to examine the latest evidence-based medicine for the various applications of RFN, including cervical, thoracic, lumbar spine; posterior sacroiliac joint pain; hip and knee joints; and occipital neuralgia. Best practice guidelines, evidence and consensus grading were provided for each anatomical target.

A Prospective, Multi-Center, Clinical Trial of a 10-kHz Spinal Cord Stimulation System in the Treatment of Chronic Pelvic Pain.

BACKGROUND: Chronic pelvic pain (CPP) is a debilitating condition that often leads to disability and does not respond to conventional treatments. This study was conducted to evaluate the effects of paresthesia-independent 10-kHz spinal cord stimulation (SCS) in subjects with CPP. METHODS: This prospective, single-arm pilot study enrolled subjects with clinical diagnoses of CPP and mean pain scores of ≥ 5.0 cm on a 10-cm VAS. Subjects underwent trial stimulations with 10-kHz SCS, and those who had successful trial stimulations (≥40% pain relief) received permanently implanted devices and were followed for 12 months. RESULTS: Of the 21 subjects who underwent the 10-kHz SCS trial, 17 were successful and 14 subjects received permanent implants. No neurological deficits were observed in any subjects and all adverse events (AEs) were resolved without sequelae during the study period. Over 12 months, mean VAS scores decreased by 72% from baseline, and 10 of 13 subjects (77%) were responders (≥50% pain relief). Pain remission (VAS score ≤ 3.0 cm) was reported by 8 of 13 subjects (62%), and mean pain scores on the short-form McGill Pain Questionnaire 2 decreased as well. Pain Disability Index scores declined by 29 points, and 85% of the subjects reported satisfaction. CONCLUSIONS: Paresthesia-independent stimulation with 10-kHz SCS reduced pelvic pain in subjects with CPP and was not associated with any unexpected AEs. While larger, controlled studies are needed, results of this study suggest that this therapeutic modality could potentially treat patients with CPP while improving their quality of life.

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro.

This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15-120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.

Adverse events of conscious sedation in ambulatory spine procedures.

BACKGROUND CONTEXT: Interventional spine procedures are commonly performed in the ambulatory surgical setting, often using conscious sedation. The rate of adverse events with conscious sedation has not been previously assessed in the interventional spine procedure setting. PURPOSE: The goal of this study was to determine the rate of adverse events when using conscious sedation in the ambulatory interventional spine setting. STUDY DESIGN: A retrospective cohort chart review analysis was performed on all interventional spine procedures performed during one calendar year at a university-affiliated ambulatory surgery center by six nonanesthesia-trained spine interventionalists. PATIENT SAMPLE: Of the 3,342 procedures performed that year, 2,494 charts (74.6%) were available for review. OUTCOME MEASURES: Adverse events were documented immediately after the procedure and at a maximum 3-day follow-up phone call. METHODS: The rate and type of adverse events were analyzed and compared between those who received conscious sedation with local anesthesia and those who received local anesthesia alone. RESULTS: Of the 2,494 cases reviewed, 1,228 spine procedures were performed with local anesthesia and conscious sedation, and 1,266 procedures were performed with local anesthesia alone. Of these cases, 66 immediate adverse events (5.12%) were documented in the conscious sedation group, and 61 immediate adverse events (4.82%) were documented in the local anesthesia alone group. At maximum 3-day follow-up, 670 patients of the conscious sedation group were available for contact, and 699 patients were available from the local anesthesia group. Thirty-two adverse events (4.77%) were noted in the conscious sedation group, and 28 adverse events (4.00%) were noted in the local anesthesia group. Comparison of these rates found no significant statistical difference. However, patients in the local anesthesia group had a significantly higher rate of postoperative hypertension. Adverse events reported both immediately and at follow-up were determined to be mild, with no serious adverse events reported. CONCLUSION: The findings of this study suggest that mild to moderate conscious sedation in interventional spine procedures is associated with low rates of adverse events when established protocols are followed.