Five-Year Longitudinal Follow-Up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Catheter Tip-Associated Mass With Continuous Infusion of Sufentanil for Persistent Spinal Pain Syndrome Type 2: A Case Report Including Histopathologic Examination and Review of the Associated Basic and Clinical Research.

OBJECTIVES: Intrathecal opioids delivered by implanted pumps are used to treat malignant or nonmalignant chronic pain. In this study, we 1) review a case in which intrathecal infusions of sufentanil along with other adjuvants were used and after an extended period led to an intrathecal mass and 2) compared and contrasted the potential mechanisms for these phenomena. MATERIALS AND METHODS: A woman aged 66 years with a history of scoliosis and multiple spine surgeries was treated with an implantable drug delivery system for treating persistent pain after laminectomy. The patient received intrathecal medication comprising sufentanil, bupivacaine, and clonidine. RESULTS: Intrathecal therapy over approximately ten years served to reduce pain and improve function over the treatment period. After the extended treatment interval, the patient developed an intrathecal mass that was associated with impairment. The mass was surgically removed. Systematic histopathology revealed the space-occupying mass to largely comprise fibroblasts and some inflammatory cells embedded in a collagen mass located proximally to the catheter tip. CONCLUSIONS: To our knowledge, this is the first published case report of sufentanil causing this complication. The science and mechanism of intrathecal catheter tip-associated mass formation and associated clinical research correlates are reviewed in detail, and explanations for this phenomenon are proposed based on histochemical analysis of the patient's pathology findings.

Optimizing an mHealth Program to Promote Type 2 Diabetes Prevention in High-Risk Individuals: Cross-Sectional Questionnaire Study.

BACKGROUND: We evaluated the outcomes of a pilot SMS text messaging-based public health campaign that identified social networking nodes and variations of response rates to develop a list of variables that could be used to analyze and develop an outreach strategy that would maximize the impact of future public health campaigns planned for Kuwait. Computational analysis of connections has been used to analyze the spread of infectious diseases, dissemination of new thoughts and ideas, efficiency of logistics networks, and even public health care campaigns. Percolation theory network analysis provides a mathematical alternative to more established heuristic approaches that have been used to optimize network development. We report on a pilot study designed to identify and treat subjects at high risk of developing type 2 diabetes mellitus in Kuwait. OBJECTIVE: The aim of this study was to identify ways to optimize efficient deployment of resources and improve response rates in a public health campaign by using variables identified in this secondary analysis of our previously published data (Alqabandi et al, 2020). This analysis identified key variables that could be used in a computational analysis to plan for future public health campaigns. METHODS: SMS text message screening posts were sent inviting recipients to answer 6 questions to determine their risk of developing type 2 diabetes mellitus. If subjects agreed to participate, a link to the Centers for Disease Control and Prevention prediabetes screening test was automatically transmitted to their mobile devices. The phone numbers used in this campaign were recorded and compared to the responses received through SMS text messaging and social media forwarding. RESULTS: A total of 180,000 SMS text messages through 5 different campaigns were sent to 6% of the adult population in Kuwait. A total of 260 individuals agreed to participate, of which 153 (58.8%) completed the screening. Remarkably, 367 additional surveys were received from individuals who were not invited by the original circulated SMS text messages. These individuals were invited through forwarded surveys from the original recipients after authentication with the study center. The original SMS text messages were found to successfully identify influencers in existing social networks to improve the efficacy of the public health campaign. CONCLUSIONS: SMS text messaging-based health care screening campaigns were found to have limited effectiveness alone; however, the increased reach through shared second-party forwarding suggests the potential of exponentially expanding the reach of the study and identifying a higher percentage of eligible candidates through the use of percolation theory. Future research should be directed toward designing SMS text messaging campaigns that support a combination of SMS text message invitations and social networks along with identification of influential nodes and key variables, which are likely unique to the environment and cultural background of the population, using percolation theory modeling and chatbots.

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial.

OBJECTIVE: This study aimed to assess the safety and effectiveness of a new charge-distributed multiphase stimulation paradigm during an extended spinal cord stimulation (SCS) trial. MATERIALS AND METHODS: This prospective, multicenter, randomized, single-blind, feasibility study included participants with chronic low back and/or leg pain and baseline numerical rating scale (NRS) for overall pain intensity ≥6. After a successful commercial SCS trial, participants were randomized to multiphase SCS therapy A (approximately 600-1500 Hz) or B (approximately 300-600 Hz), delivered via an investigational external pulse generator and existing leads during an 11-to-12-day testing period. Primary end points were mean NRS change from baseline to final in-office visit for each multiphase therapy and between therapies. Secondary end points included mean NRS change from end of commercial trial to final study visit and incidence of device-related adverse events (AEs). Additional measures included patient-reported outcomes collected at home through electronic watches and written diaries. Power usage was compared between multiphase and commercial therapies. RESULTS: A total of 122 participants initiated a commercial trial; 77 were randomized to a multiphase arm, and 65 completed the study. Reductions in mean NRS scores from baseline to final study visit were significant for multiphase therapy A and B (-4.3 and -4.7, respectively; both p < 0.0001). There was no statistically significant difference in mean NRS reduction or percent pain relief between multiphase therapies. In an additional analysis, 63.9% of participants reported greater pain relief with multiphase than with commercial SCS therapy in the at-home setting. On average, multiphase required less power than did commercial devices. One non-serious device-related AE was reported, and no infections occurred during the extended trial. CONCLUSIONS: Multiphase SCS effectively reduced pain in participants with chronic low back and/or leg pain during a trial, with no unanticipated device-related AEs reported. Future studies should evaluate long-term effectiveness of multiphase stimulation. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03594266.

Race differences in pain and pain-related risk factors among former professional American-style football players.

ABSTRACT: The burden of pain is unequal across demographic groups, with broad and persisting race differences in pain-related outcomes in the United States. Members of racial and ethnic minorities frequently report more pervasive and severe pain compared with those in the majority, with at least some disparity attributable to differences in socioeconomic status. Whether race disparities in pain-related health outcomes exist among former professional football players is unknown. We examined the association of race with pain outcomes among 3995 former professional American-style football players who self-identified as either Black or White. Black players reported more intense pain and higher levels of pain interference relative to White players, even after controlling for age, football history, comorbidities, and psychosocial factors. Race moderated associations between several biopsychosocial factors and pain; higher body mass index was associated with more pain among White but not among Black players. Fatigue and psychosocial factors were more strongly related to pain among Black players relative to White players. Collectively, the substantial social and economic advantages of working as a professional athlete did not seem to erase race-related disparities in pain. We highlight an increased burden of pain among elite Black professional football players and identify race-specific patterns of association between pain and biopsychosocial pain risk factors. These findings illuminate potential future targets of interventions that may serve to reduce persistent disparities in the experience and impact of pain.

Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial.

BACKGROUND: Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. OBJECTIVE: This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. RESULTS: At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. CONCLUSIONS: At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The study is registered on clinicaltrials.gov with identifier NCT02577354.

Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

Higher Pain Sensitivity Predicts Efficacy of a Wearable Transcutaneous Electrical Nerve Stimulation Device for Persons With Fibromyalgia: A Randomized Double-Blind Sham-Controlled Trial.

OBJECTIVES: This study investigated the efficacy of a transcutaneous electrical nerve stimulation (TENS) device (Quell®) for persons with symptoms due to fibromyalgia (FM). MATERIALS AND METHODS: One hundred nineteen (N = 119) subjects were randomly assigned to use an active (N = 62) or sham (N = 57) TENS for three months. All subjects completed baseline questionnaires and were administered quantitative sensory testing (QST). Subjects completed the Patients' Global Impression of Change (PGIC, primary outcome measure) and other mailed questionnaires (secondary outcome measures) at six weeks and three months. RESULTS: The subjects averaged 50.4 ± 13.5 years of age, 93.3% were female, and 79.8% were Caucasian. Most showed benefit from using the TENS, but no differences between groups were found on the primary outcome measure after three months (active 3.87 ± 1.85, sham 3.73 ± 1.80, 95% confidence interval [CI] [-0.60, 0.88], p = 0.707). Those with more hypersensitivity showed most improvement on the PGIC at six weeks (0.22, 95% CI [0.01, 0.43], p = 0.042) and three months (0.20, 95% CI [0.00, 0.41], p = 0.049) and among those with higher sensitivity based on QST, the active TENS group showed the most benefit with TENS compared with the sham treatment (1.20, 95% CI [0.22, 2.18], p = 0.017). No TENS-related serious adverse events were reported. Subjects in the sham group correctly identified their treatment 87.5% of the time, while, surprisingly, subjects in the active group correctly identified their treatment only 17.4% of the time. CONCLUSION: This study found no differences between those who were exposed to maximal-frequency active stimulation or minimal-frequency sham stimulation from a wearable TENS in reducing FM-related symptoms. However, those with greater hypersensitivity showed most benefit from TENS. Additional studies to help determine the role individual differences play in the use of TENS in managing FM-related symptoms are needed.

Improved Treatment Effect of Triamcinolone Acetonide Extended-Release in Patients with Concordant Baseline Pain Scores on the Average Daily Pain and Western Ontario and McMaster Universities Osteoarthritis Index Pain Scales.

INTRODUCTION: A phase 3 randomized controlled study comparing triamcinolone acetonide extended-release (TA-ER) to conventional TA crystalline suspension (TAcs) reported variable efficacy results. Enrollment criteria may have contributed to this discrepancy, as moderate-to-severe average daily pain (ADP) was required at baseline, whereas no limitations were placed on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A) pain severity. We conducted a post hoc sensitivity analysis to compare treatment effects in patients reporting moderate-to-severe osteoarthritis (OA) pain on both scales. METHODS: Participants > 40 years old with symptomatic knee OA were randomly assigned to a single intra-articular injection of TA-ER 32 mg, TAcs 40 mg, or saline-placebo and followed for 24 weeks. Patient-reported ADP, WOMAC-A, rescue medication usage, and adverse events (AEs) were assessed. Participants who reported moderate-to-severe OA pain at baseline using both instruments (ADP ≥ 5 to ≤ 9, maximum 10 and WOMAC-A ≥ 2, maximum 4) were categorized as "concordant" pain reporters; patients with baseline moderate-to-severe OA on ADP only were termed "discordant" pain reporters. RESULTS: Two-hundred-ninety-two concordant pain reporters of 484 total subjects received TA-ER 32 mg (n = 95), TAcs 40 mg (n = 100), or saline-placebo (n = 97). Baseline characteristics and AE profiles of the concordant and discordant pain responders were consistent with the full analysis population. Among concordant pain reporters, TA-ER significantly (p < 0.05) improved ADP scores vs. TAcs (weeks 5-19; area-under-the-effect [AUE]weeks1-12; AUEweeks1-24) and saline-placebo (weeks 1-20; AUEweeks1-12; AUEweeks1-24). At week 12, a higher proportion reported no knee pain (ADP = 0) with TA-ER (~ 28%) vs. TAcs (~ 8%). TA-ER significantly improved WOMAC-A vs. TAcs at weeks 4, 8, and 12, with significant reduction in rescue medication usage observed with TA-ER from weeks 2 to 20 vs. TAcs. CONCLUSIONS: In patients reporting moderate-to-severe knee OA pain at baseline based on concordant ADP and WOMAC-A scores, TA-ER provided statistically significant pain relief for ≥ 12 weeks compared with conventional TAcs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02357459.

Osteoarthritis is a chronic condition that greatly impacts patients. Pain is the most common symptom of osteoarthritis. Clinical trials evaluating the effects of new drugs to treat osteoarthritis pain frequently use scales to rate overall pain following treatment. Patients may rate their pain using a number that best describes their pain, with the lowest number typically meaning "no pain," and the highest number typically meaning "pain as bad as you can imagine." Other rating scales may be used to rate pain in situations commonly associated with osteoarthritis.Results from a large clinical trial demonstrated that injection of an extended-release steroid significantly reduced pain compared with a conventional steroid injection on only one of the two pain-reporting scales used in the trial. A closer look found that some patients reported their pain differently on the two rating scales at the start of the trial, with some reporting moderate-to-severe pain using one questionnaire and mild pain using the other. Here, we focused on those patients who reported having moderate-to-severe osteoarthritis knee pain on both pain scales at the start and found that the pain relief benefit associated with the extended-release steroid injection was greatly improved compared with the conventional steroid injection with both measures. Patients receiving the extended-release steroid injection also decreased their use of rescue medication for pain relief.

An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial.

ABSTRACT: Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, -3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain.

Effects of Wearable Transcutaneous Electrical Nerve Stimulation on Fibromyalgia: A Randomized Controlled Trial.

PURPOSE: Fibromyalgia is a chronic condition characterized by widespread pain and interference with daily activities. The aim of this study is to assess the benefit of transcutaneous electrical nerve stimulation (TENS) for persons diagnosed with fibromyalgia. PATIENTS AND METHODS: Adults meeting diagnostic criteria for fibromyalgia were randomized in a double-blind trial to receive either an active (n=62) or sham (n=57) wearable TENS device for 3-months. Subjects were classified as having lower or higher pain sensitivity by Quantitative Sensory Testing (QST). Patient Global Impression of Change (PGIC, primary outcome) and secondary efficacy measures including Fibromyalgia Impact Questionnaire (FIQR), Brief Pain Inventory (BPI) and painDETECT questionnaire (PDQ) were assessed at baseline, 6-weeks and 3-months. Treatment effects were determined by a mixed model for repeated measures (MMRM) analysis of the intention-to-treat (ITT) population (N=119). A pre-specified subgroup analysis of pain sensitivity was conducted using an interaction term in the model. RESULTS: No differences were found between active and sham treatment on PGIC scores at 3-months (0.34, 95% CI [-0.37, 1.04], p=0.351) in the ITT population. However, in subjects with higher pain sensitivity (n=60), PGIC was significantly greater for active treatment compared to sham (1.19, 95% CI [0.24, 2.13], p=0.014). FIQR total score (-7.47, 95% CI [-12.46, -2.48], p=0.003), FIQR pain item (-0.62, 95% CI [-1.17, -0.06], p=0.029), BPI Interference (-0.70, 95% CI [-1.30, -0.11], p=0.021) and PDQ (-1.69, 95% CI [-3.20, -0.18], p=0.028) exhibited significant improvements for active treatment compared to sham in the ITT population. Analgesics use was stable and comparable in both groups. CONCLUSION: This study demonstrated modest treatment effects of reduced disease impact, pain and functional impairment from wearable TENS in individuals with fibromyalgia. Subjects with higher pain sensitivity exhibited larger treatment effects than those with lower pain sensitivity. Wearable TENS may be a safe treatment option for people with fibromyalgia. CLINICALTRIALSGOV REGISTRATION: NCT03714425.

Establishment of an Individualized Chronotherapy, Autonomic Nervous System, and Variability-Based Dynamic Platform for Overcoming the Loss of Response to Analgesics.

BACKGROUND: Control of chronic pain and mainly the partial or complete loss of response to analgesics is a major unmet need. Multiple mechanisms underline the development of tolerance to analgesics in general and specifically to opioids. The autonomic nervous system (ANS) plays a role in the development of analgesic tolerance and chronobiology. OBJECTIVES: To review the mechanisms associated with the development of nonresponsiveness to analgesics. STUDY DESIGN: Literature review. SETTING: The review is followed by a description of a new method for overcoming resistance and improving the response to analgesics. METHODS: Conducted a detailed review of the relevant studies describing the mechanisms that underlie tolerance to pain medications, and the potential roles of the ANS and chronobiology in the development of drug resistance. RESULTS: The autonomic balance is reflected by heart rate variability, an example of a fundamental variability that characterizes biological systems. Chronotherapy, which is based on the circadian rhythm, can improve the efficacy and reduce the toxicity of chronic medications. In this article, we present the establishment of an individualized variability- and chronobiology-based therapy for overcoming the compensatory mechanisms associated with a loss of response to analgesics. We describe the premise of implementing personalized signatures associated with the ANS, and chronobiology, as well as with the pathophysiology of pain for establishing an adaptive model that could improve the efficacy of opioids, in a highly dynamic system. LIMITATIONS: The studies presented were selected based on their relevance to the subject. CONCLUSIONS: The described variability-based system may ensure prolonged effects of analgesics while reducing the toxicity associated with increasing dosages.

Online group pain management for chronic pain: Preliminary results of a novel treatment approach to teletherapy.

OBJECTIVE: This pilot study was designed to determine the feasibility, tolerability, safety, and efficacy of group teletherapy for persons with chronic pain. The aim was to present preliminary outcomes of an open trial of group cognitive behavioural therapy (CBT) teletherapy compared with an in-person chronic pain patient group. METHODS: We recruited 47 chronic pain patients to participate in an 8-session, 2-hour-per-week, online, structured, CBT-oriented pain management group using WebEx and compared them with 46 subjects who participated in a parallel, content-matched, in-person, weekly group. Both groups included goal setting, skills training, relaxation exercises, group discussion, and practice assignments. All subjects completed baseline measures, which were repeated post-treatment. Those in the online group participated in weekly telephone interviews and rated the perceived helpfulness of the remote group. RESULTS: The average age of the online group participants was 54.5 ( ± 14.3) years and 70.2% were female, compared with 59.7 ( ± 13.0) years of age and 57.8% females among the in-person group members. On follow-up, both CBT groups showed modest improvements on the outcome measures. Results of this preliminary investigation comparing online teletherapy with in-person CBT suggest similar benefit. Many participants in the online group rated their experience as very helpful (62.5%; 7-10/10) and most would recommend this programme to others (93.7%; 7-10/10). DISCUSSION: Preliminary findings suggest that online group CBT may be as effective in improving coping among persons with chronic pain as in-person groups. More rigorous controlled trials are needed to adequately assess the outcome benefit of online teletherapy for chronic pain.

Secondary Impact of Social Media via Text Message Screening for Type 2 Diabetes Risk in Kuwait: Survey Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an international problem of alarming epidemic proportions. T2DM can develop due to multiple factors, and it usually begins with prediabetes. Fortunately, this disease can be prevented by following a healthy lifestyle. However, many health care systems fail to properly educate the public on disease prevention and to offer support in embracing behavioral interventions to prevent diabetes. SMS messaging has been combined with cost-effective ways to reach out to the population at risk for medical comorbidities. To our knowledge, the use of nationwide SMS messaging in the Middle East as a screening tool to identify individuals who might be at risk of developing T2DM has not been reported in the literature. OBJECTIVE: The primary aim of this study was to assess the feasibility of conducting a series of SMS messaging campaigns directed at random smartphone users in Kuwait for the detection and prevention of T2DM. It was predicted that 1% of those receiving the text message would find it relevant and participate in the study. The secondary aim of this study was to assess the incidence of participation of those who were forwarded the initial text message by family members and friends. METHODS: In this study, 5 separate text message screening campaigns were launched inviting recipients to answer 6 questions to determine the risk of developing T2DM. If subjects agreed to participate, a link to the prediabetes screening test devised by the Centers for Disease Control and Prevention was automatically transmitted to their mobile devices. Those identified as high risk were invited to participate in a diabetes prevention program. RESULTS: A total of 180,000 SMSs were sent to approximately 6% of the adult population in Kuwait. Of these, 0.14% (260/180,000) of the individuals who received the SMS agreed to participate, of whom 58.8% (153/260) completed the screening. Surprisingly, additional surveys were completed by 367 individuals who were invited via circulated SMS messages forwarded by family members and friends. Altogether, 23.3% (121/520) qualified and agreed to participate in a diabetes prevention program. The majority of those who chose to participate in the prevention program were overweight, aged 45-65 years, and reported being less physically active than those who chose not to participate (χ22=42.1, P<.001). CONCLUSIONS: Although health care screening via text messaging was found to have limited effectiveness by itself, it exhibited increased reach through shared second-party social media messaging. Despite the fact a subpopulation at possible risk of developing T2DM could be reached via text messaging, most responders were informed about the screening campaign by family and friends. Future research should be designed to tap into the benefits of social media use in health risk campaigns.

Clinical Integration of a Smartphone App for Patients With Chronic Pain: Retrospective Analysis of Predictors of Benefits and Patient Engagement Between Clinic Visits.

BACKGROUND: Although many pain-related smartphone apps exist, little attention has been given to understanding how these apps are used over time and what factors contribute to greater compliance and patient engagement. OBJECTIVE: This retrospective analysis was designed to help identify factors that predicted the benefits and future use of a smartphone pain app among patients with chronic pain. METHODS: An app designed for both Android and iOS devices was developed by Brigham and Women's Hospital Pain Management Center (BWH-PMC) for users with chronic pain to assess and monitor pain and communicate with their providers. The pain app offered chronic pain assessment, push notification reminders and communication, personalized goal setting, relaxation sound files, topics of interest with psychological and medical pain management strategies, and line graphs from daily assessments. BWH-PMC recruited 253 patients with chronic pain over time to use the pain app. All subjects completed baseline measures and were asked to record their progress every day using push notification daily assessments. After 3 months, participants completed follow-up questionnaires and answered satisfaction questions. We defined the number of completed daily assessments as a measure of patient engagement with the pain app. RESULTS: The average age of participants was 51.5 years (SD 13.7, range 18-92), 72.8% (182/253) were female, and 36.8% (78/212) reported the low back as their primary pain site. The number of daily assessments ranged from 1 to 426 (average 62.0, SD 49.9). The app was easy to introduce among patients, and it was well accepted. Those who completed more daily assessments (greater patient engagement) throughout the study were more likely to report higher pain intensity, more activity interference, and greater disability and were generally overweight compared with others. Patients with higher engagement with the app rated the app as offering greater benefit in coping with their pain and expressed more willingness to use the app in the future (P<.05) compared with patients showing lower engagement. Patients completing a small number of daily assessments reported less pain intensity, less daily activity interference, and less pain-related disability on average and were less likely to use the two-way messaging than those who were more engaged with the pain app (P<.05). CONCLUSIONS: Patients with chronic pain who appeared to manage their pain better were less likely to report benefits of a smartphone pain app designed for chronic pain management. They demonstrated lower patient engagement in reporting their daily progress, in part, owing to the perceived burden of regularly using an app without a perceived benefit. An intrinsically different pain app designed and targeted for individuals based on early identification of user characteristics and adapted for each individual would likely improve compliance and app-related patient engagement.

Does bedtime matter among patients with chronic pain? A longitudinal comparison study.

INTRODUCTION: Chronic pain patients frequently report having sleep disturbances and many tend to stay up during the night and then sleep into the day. OBJECTIVES: This study was designed to compare a heterogeneous group of persons with chronic pain who reported typically going to bed between the hours of 9 pm and midnight with those who go to bed at other hours of the day and night. METHODS: Two hundred seventy-nine participants were divided between those who reported going to bed between the hours of 9 pm and midnight (N = 205) and those who reported having atypical bedtimes (N = 74) based on pre-post questionnaire data and average pain assessments from a smartphone pain application (app). RESULTS: Those individuals in the atypical bedtime group reported waking up more frequently and getting fewer hours sleep (P < 0.05). These individuals also reported significantly higher pain scores, activity interference, and taking more prescription opioid medication compared with those who had typical bedtimes (P < 0.05). Based on average 3-month daily assessments, those subjects with an atypical bedtime consistently reported more sleep disturbances, pain, activity interference, negative mood, and general worsening conditions over time, and elevated pain catastrophizing, pain-related disability, emotional distress scores, and more prescription medication for pain at 3-month follow-up (P < 0.01). CONCLUSION: These results support the importance of providers asking patients with pain about what time they typically go to bed at night to gain a greater understanding of their lifestyle habits. Future studies are needed to further determine the importance of maintaining a typical bedtime among patients with chronic pain.

Outcome of a High-Frequency Transcutaneous Electrical Nerve Stimulator (hfTENS) Device for Low Back Pain: A Randomized Controlled Trial.

OBJECTIVE: This controlled trial examined the benefit of a high-frequency transcutaneous electrical nerve stimulation (hfTENS) device (the Quell, NeuroMetrix, Inc., Waltham, MA, U.S.A.) for patients with chronic low back pain (CLBP). METHODS: Thirty-five (n = 35) participants were randomly assigned to use the device each day for 3 months (experimental group) and were compared with 33 subjects without the device (treatment-as-usual control group). All patients were instructed to complete baseline questionnaires and were assessed on thresholds of pressure pain and mechanical temporal summation as part of standardized quantitative sensory testing (QST). The subjects also uploaded smartphone applications (apps) for tracking use of the hfTENS and for daily pain assessment. Each participant completed weekly phone interviews, was prompted to complete daily pain app assessments, and was asked to repeat the baseline questionnaires again after 6 weeks and 3 months. RESULTS: Sixty percent of the subjects were female, 77.9% were Caucasian, and the average age was 46.2 years. Significant reductions in pain intensity (P < 0.01) and activity interference (P < 0.025) and significant improvements in pain catastrophizing (P < 0.025) were noted in the experimental group compared with the control group. No group differences were found on depression, anxiety, or pain-related disability. Older subjects with a longer duration of pain tended to use the hfTENS more often. Subjects who showed greater sensitivity based on QST results revealed increased use of the hfTENS (P < 0.025) and tended to believe that the hfTENS was more helpful in reducing their back pain, but these findings did not reach significance (P = 0.09). CONCLUSION: These results suggest that hfTENS can have a moderate effect in reducing pain and improving quality of life in low back pain patients. Further trials designed to determine the mechanism of action of the hfTENS are needed.

Determining Pain Catastrophizing From Daily Pain App Assessment Data: Role of Computer-Based Classification.

This study compared persons with chronic pain who consistently reported that their pain was worsening with those who reported that their pain was improving or remaining the same per daily assessment data from a smartphone pain app. All participants completed baseline measures and were asked to record their progress every day by answering whether their overall condition had improved, remained the same, or gotten worse (perceived change) on a visual analogue scale. One hundred forty-four individuals with chronic pain who successfully entered daily assessments were included. Those persons who were classified as worse showed significantly higher pain intensity scores, greater activity interference, higher disability and mood disturbance scores, and higher scores on the Pain Catastrophizing Scale both at baseline and after 3 months (P < .001). Repeated measures analyses and multilevel modeling of perceived change data over different time intervals of 20 assessments over 40 days, 10 assessments over 20 days, and 5 assessments over 10 days were examined. These analyses demonstrated that group classification of better, same, and worse could be reliably determined, even with as few as 5 assessments. These results support the use of innovative mobile health technology to identify individuals who are prone to catastrophize about their pain. Perspective: This study demonstrated that daily assessment of overall perceived change with a smartphone pain app was positively correlated with the Pain Catastrophizing Scale and capturing short-term daily assessment trends data using computer-based classification methods might be a future way to help to identify individuals who tend to catastrophize about their pain.

Unique Intradural Inflammatory Mass Containing Precipitated Morphine: Confirmatory Analysis by LESA-MS and MALDI-MS.

Opioids are often used for analgesia via continuous intrathecal delivery by implantable devices. A higher concentration and daily dose of opioid have been postulated as risk factors for intrathecal granuloma formation. We present a 42-year-old female patient with chronic abdominal pain from refractory pancreatitis, with an intrathecal drug delivery device implanted 21 years prior, delivering continuous intrathecal morphine. After many years without concerning physical signs or complaints, with gradual increases in daily morphine dose, she presented with rapidly progressive neurologic deficits, including lower extremity, bladder, and bowel symptoms. These symptoms were determined to be secondary to mass effect and local inflammation related to an intrathecal catheter tip granuloma, detected on magnetic resonance imaging of the spine. The mass was urgently resected. On histopathologic examination, this granuloma was found to be unique, in that in addition to the expected inflammatory components, it appeared to contain precipitated nonpolarizable crystals. These were identified as precipitated morphine using liquid extraction surface analysis-tandem mass spectrometry (LESA-MS/MS) and matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance-mass spectrometry imaging (MALDI-FTICR-MSI). In addition to the unique finding of precipitated morphine crystals, the long-term follow-up of both morphine concentration and daily dose increases provides insight into the formation of intrathecal granulomas.