Proposing a framework to quantify the potential impact of pharmacokinetic drug-drug interactions caused by a new drug candidate by using real world data about the target patient population.

Drug development teams must evaluate the risk/benefit profile of new drug candidates that perpetrate drug-drug interactions (DDIs). Real-world data (RWD) can inform this decision. The purpose of this study was to develop a predicted impact score for DDIs perpetrated by three hypothetical drug candidates via CYP3A, CYP2D6, or CYP2C9 in type 2 diabetes mellitus (T2DM), obesity, or migraine. Optum Market Clarity was analyzed to estimate use of CYP3A, CYP2D6, or CYP2C9 substrates classified in the University of Washington Drug Interaction Database as moderate sensitive, sensitive, narrow therapeutic index, or QT prolongation. Scoring was based on prevalence of exposure to victim substrates and characteristics (age, polypharmacy, duration of exposure, and number of prescribers) of those exposed. The study population of 14,163,271 adults included 1,579,054 with T2DM, 3,117,753 with obesity, and 410,436 with migraine. For T2DM, 71.3% used CYP3A substrates, 44.3% used CYP2D6 substrates, and 44.3% used CYP2C9 substrates. For obesity, 57.1% used CYP3A substrates, 34.6% used CYP2D6 substrates, and 31.0% used CYP2C9 substrates. For migraine, 64.1% used CYP3A substrates, 44.0% used CYP2D6 substrates, and 28.9% used CYP2C9 substrates. In our analyses, the predicted DDI impact scores were highest for DDIs involving CYP3A, followed by CYP2D6, and CYP2C9 substrates, and highest for T2DM, followed by migraine, and obesity. Insights from RWD can be used to estimate a predicted DDI impact score for pharmacokinetic DDIs perpetrated by new drug candidates currently in development. This score can inform the risk/benefit profile of new drug candidates in a target patient population.

NAFLD and NASH are obesity-independent risk factors in COVID-19: Matched real-world results from the large PINC AI™ Healthcare Database.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are potential risk factors for severe pneumonia and other infections. Available data on the role of NAFLD/NASH in worsening outcomes for COVID-19 are controversial and might be confounded by comorbidities. METHODS: We used the PINC AI™ Healthcare Data Special Release (PHD-SR) to identify patients with COVID-19 (ICD-10) at approximately 900 hospitals in the United States. We performed exact matching (age, gender, and ethnicity) for patients with or without NAFLD/NASH, adjusting for demographics (admission type, region) and comorbidities (e.g., obesity, diabetes) through inverse probability of treatment weighting and then analysed hospitalisation-related outcomes. RESULTS: Among 513 623 patients with SARS-CoV-2 (COVID-19), we identified 14 667 with NAFLD/NASH who could be matched to 14 667 controls. Mean age was 57.6 (±14.9) years, 50.8% were females and 43.7% were non-Hispanic whites. After matching, baseline characteristics (e.g., age, ethnicity, and gender) and comorbidities (e.g., hypertension, obesity, diabetes, and cardiovascular disease) were well balanced (standard difference (SD) <.10), except for cirrhosis and malignancies. Patients with COVID-19 and NAFLD/NASH had higher FIB-4 scores, a significantly longer hospital length of stay (LOS) and intensive care LOS than controls (9.4 vs. 8.3 days, and 10.4 vs. 9.3, respectively), even after adjusting for cirrhosis and malignancies. Patients with COVID-19 and NAFLD/NASH also had significantly higher risk of needing invasive mandatory ventilation (IMV) (odds ratio 1.0727; 95% CI 1.0095-1.1400). Other outcomes were similar in both groups. CONCLUSIONS: In this large real-world cohort of patients hospitalised for COVID-19 in the United States, NAFLD/NASH were obesity-independent risk factors for complicated disease courses.

Use of Real-World Evidence to Drive Drug Development Strategy and Inform Clinical Trial Design.

Interest in real-world data (RWD) and real-world evidence (RWE) to expedite and enrich the development of new biopharmaceutical products has proliferated in recent years, spurred by the 21st Century Cures Act in the United States and similar policy efforts in other countries, willingness by regulators to consider RWE in their decisions, demands from third-party payers, and growing concerns about the limitations of traditional clinical trials. Although much of the recent literature on RWE has focused on potential regulatory uses (e.g., product approvals in oncology or rare diseases based on single-arm trials with external control arms), this article reviews how biopharmaceutical companies can leverage RWE to inform internal decisions made throughout the product development process. Specifically, this article will review use of RWD to guide pipeline and portfolio strategy; use of novel sources of RWD to inform product development, use of RWD to inform clinical development, use of advanced analytics to harness "big" RWD, and considerations when using RWD to inform internal decisions. Topics discussed will include the use of molecular, clinicogenomic, medical imaging, radiomic, and patient-derived xenograft data to augment traditional sources of RWE, the use of RWD to inform clinical trial eligibility criteria, enrich trial population based on predicted response, select endpoints, estimate sample size, understand disease progression, and enhance diversity of participants, the growing use of data tokenization and advanced analytical techniques based on artificial intelligence in RWE, as well as the importance of data quality and methodological transparency in RWE.

Impact of treatment with liposomal bupivacaine on hospital costs, length of stay, and discharge status in patients undergoing total knee arthroplasty at high-use institutions.

Aims: Post-surgical pain experienced by patients undergoing total knee arthroplasty (TKA) can be severe. Enhanced recovery after surgery programs incorporating multimodal analgesic regimens have evolved in an attempt to improve patient care while lowering overall costs. This study examined clinical and economic outcomes in hospitals using liposomal bupivacaine (LB) for pain control following TKA.Methods: This retrospective observational study utilized hospital chargemaster data from the Premier Healthcare Database from January 2011 through April 2017 for the 10 hospitals with the highest number of primary TKA procedures using LB. Within these hospitals, patients undergoing TKA who received LB were propensity-score matched in a 1:1 ratio to a control group not receiving LB. Outcomes included hospital length of stay (LOS), discharge status, 30-day same-hospital readmissions, total hospitalization costs, and opioid consumption; only patients with Medicare or commercial insurance as the primary payer for TKA were considered.Results: The study population included 20,907 Medicare-insured patients (LB = 10,411; control =10,496) and 12,505 patients with commercial insurance (LB = 6,242; control = 6,263). Overall, LOS was 0.6 days shorter with LB (p < 0.0001), and patients who received LB were 1.6-times more likely to be discharged home (p < 0.0001). Total hospitalization costs for the TKA procedure were lower with LB for patients with both Medicare (-$616; P < 0.0001) and commercial insurance (-$775; p < 0.0001). Opioid consumption was lower with LB in both payer populations (p < 0.0001). No significant differences for 30-day readmissions were found.Limitations: Costs were estimated using Premier charge-to-cost ratios and limited to goods and services recorded in the chargemaster. Findings from these 10 hospitals may not be representative of other US hospitals.Conclusions: In a sub-set of 10 US hospitals with the highest use of LB for TKA, LB use was associated with shorter hospital LOS, increased home discharge, lower total hospitalization costs, and decreased opioid use after TKA.

Complementary and alternative medicine: A survey of its use in children with chronic respiratory illness.

BACKGROUND: The use of complementary and alternative medicine (CAM) has increased in recent years, with especially high prevalence in individuals with chronic illnesses. In the United States, the prevalence of CAM use in pediatric asthma patients is as high as 89%. OBJECTIVE: To investigate the epidemiology of pediatric CAM use in respiratory subspecialty clinics. METHODS: A survey was conducted at two hospital-based respiratory clinics in Edmonton (Alberta) and Ottawa (Ontario). Caregivers (most often parents) of children <18 years of age were asked questions regarding child and caregiver use of CAM, including products and practices used, beliefs about CAM, trust in information sources about CAM and characteristics of the respondents themselves. RESULTS: A total of 202 survey questionnaires were completed (151 from Edmonton and 51 from Ottawa). Pediatric CAM use in Edmonton was 68% compared with 45% in Ottawa, and was associated with caregiver CAM use, poorer health and health insurance coverage for CAM. The majority (67%) of children using CAM had taken prescription drugs concurrently and 58% of caregivers had discussed this with their doctor. DISCUSSION: Lifetime use of CAM at these pediatric clinics was higher than reported for children who do not have chronic diseases. CAM practices that are popular may be worthy of further research to evaluate their effectiveness and safety profile with regard to drug interactions. Health care providers should be encouraged to discuss CAM use at every visit, and explore their patient's health-related beliefs, behaviours and treatment preferences.

HISTORIQUE: L'utilisation de la médecine complémentaire et parallèle (MCP) a augmenté ces dernières années. Sa prévalence est particulièrement élevée chez les personnes atteintes d'une maladie chronique. Aux États-Unis, sa prévalence chez les patients asthmatiques d'âge pédiatrique atteint les 89 %. OBJECTIF: Examiner l'épidémiologie de l'utilisation de la MCP en pédiatrie dans des cliniques spécialisées en santé respiratoire. MÉTHODOLOGIE: Les chercheurs ont effectué un sondage dans deux cliniques de santé respiratoire en milieu hospitalier, à Edmonton (Alberta) et à Ottawa (Ontario). Les personnes qui s'occupaient d'enfants de 18 ans ou moins (en général, les parents) se sont fait poser des questions sur l'utilisation de la MCP par l'enfant et par elles, y compris les produits et pratiques utilisés, les croyances au sujet de la MCP, la confiance envers les sources d'information sur la MCP et leurs caractéristiques personnelles. RÉSULTATS: Au total, 202 sondages ont été remplis (151 à Edmonton et 51 à Ottawa). L'utilisation de la MCP en pédiatrie à Edmonton s'élevait à 68 %, et à 45 % à Ottawa. Elle s'associait à l'utilisation de MCP par la personne qui s'occupait de l'enfant, à une moins bonne santé et à une couverture d'assurance pour la MCP. La majorité des enfants (67 %) qui utilisaient la MCP prenaient simultanément des médicaments sur ordonnance, et 58 % des personnes qui s'occupaient d'eux en avaient parlé avec leur médecin. EXPOSÉ: À ces cliniques de pédiatrie, l'utilisation générale de MCP était plus élevée que celle déclarée chez les enfants qui n'ont pas de maladie chronique. Les pratiques de MCP qui sont populaires devraient peut-être faire l'objet de recherches supplémentaires pour en évaluer l'efficacité et le profil d'innocuité en matière d'interactions médicamenteuses. Il faut encourager les dispensateurs de soins à parler de MCP à chaque rendez-vous et à explorer les croyances de leurs patients liées à la santé, leurs comportements et leurs préférences thérapeutiques.

Complementary and alternative medicine: a survey of its use in pediatric oncology.

Background. The use of complementary and alternative medicine (CAM) is high among children and youths with chronic illnesses, including cancer. The objective of this study was to assess prevalence and patterns of CAM use among pediatric oncology outpatients in two academic clinics in Canada. Procedure. A survey was developed to ask patients (or their parents/guardians) presenting to oncology clinics at the Stollery Children's Hospital in Edmonton and the Children's Hospital of Eastern Ontario (CHEO) in Ottawa about current or previous use of CAM products and practices. Results. Of the 137 families approached, 129 completed the survey. Overall CAM use was 60.5% and was not significantly different between the two hospitals. The most commonly reported reason for not using CAM was lack of knowledge about it. The most common CAM products ever used were multivitamins (86.5%), vitamin C (43.2%), cold remedies (28.4%), teething remedies (27.5%), and calcium (23.0%). The most common CAM practices ever used were faith healing (51.0%), massage (46.8%), chiropractic (27.7%), and relaxation (25.5%). Many patients (40.8%) used CAM products at the same time as prescription drugs. Conclusion. CAM use was high among patients at two academic pediatric oncology clinics. Although most respondents felt that their CAM use was helpful, many were not discussing it with their physicians.

Delay in operative stabilization of spine fractures in multitrauma patients without neurologic injuries: effects on outcomes.

BACKGROUND: Optimal timing for surgical stabilization of the fractured spine is controversial. Early stabilization facilitates mobilization and theoretically reduces associated complications. METHODS: We identified consecutive patients without neurologic injury requiring stabilization surgery for a spinal fracture at an academic tertiary-care hospital over a 12-year period. Incidences of postoperative complications were prospectively evaluated. We analyzed results based on the time elapsed before the final surgical stabilization procedure. Multivariate analyses were performed to explore the effects of potential confounders. RESULTS: A total of 83 patients (60 men, 23 women; mean age 39.4 yr) met the eligibility criteria and were enrolled. The mean Injury Severity Score (ISS) was 27.1 (range 12.0-57.0); 35% of patients had a cervical fracture and 65% had a thoraco-lumbar fracture. No statistically significant associations were uncovered between time to surgical stabilization and age, ISS or comorbidities. Comparing patients stabilized after 24 hours with those stabilized within 24 hours, there was an almost 8-fold greater risk of a complication related to prolonged recumbency (p = 0.007). We observed similar effects for other types of complications. Delays of more than 72 hours had a negative effect on complication rates; these effects remained significant after multivariate adjustments for age, comorbidity and ISS. CONCLUSION: This study demonstrates a strong relation between timing of surgical stabilization of spinal fractures in multitrauma patients without neurologic injuries and complications. Further studies with larger samples may allow for better adjustment of potentially confounding factors and identify subgroups in which this effect is most pronounced.

Synthesis of recommendations for the assessment and management of low back pain from recent clinical practice guidelines.

BACKGROUND CONTEXT: Low back pain (LBP) is a prevalent, costly, and challenging condition to manage. Clinicians must choose among numerous assessment and management options. Several recent clinical practice guidelines (CPGs) on LBP have attempted to inform these decisions by evaluating and summarizing the best available supporting evidence. The quality and consistency of recommendations from these CPGs are currently unknown. PURPOSE: To conduct a systematic review of recent CPGs and synthesize their recommendations on assessing and managing LBP for clinicians. STUDY DESIGN/SETTING: Systematic review. METHODS: Literature search using MEDLINE, National Guidelines Clearinghouse, National Institute for Clinical Excellence, Internet search engines, and references of known articles. Only CPGs related to both assessment and management of LBP written in English were eligible; CPGs that summarized evidence from before the year 2000 were excluded. Data related to methods and recommendations for assessment and management of LBP were abstracted independently by two reviewers. Methodological quality was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument by two reviewers. RESULTS: The search uncovered 669 citations, of which 95 were potentially relevant and 10 were included in the review; 6 discussed acute LBP, 6 chronic LBP, and 6 LBP with neurologic involvement. Methods used to develop CPGs varied, but the overall methodological quality was high as defined by AGREE scores. Recommendations for assessment of LBP emphasized the importance of ruling out potentially serious spinal pathology, specific causes of LBP, and neurologic involvement, as well as identifying risk factors for chronicity and measuring the severity of symptoms and functional limitations, through the history, physical, and neurologic examination. Recommendations for management of acute LBP emphasized patient education, with short-term use of acetaminophen, nonsteroidal anti-inflammatory drugs, or spinal manipulation therapy. For chronic LBP, the addition of back exercises, behavioral therapy, and short-term opioid analgesics was suggested. Management of LBP with neurologic involvement was similar, with additional consideration given to magnetic resonance imaging or computed tomography to identify appropriate candidates willing to undergo epidural steroid injections or decompression surgery if more conservative approaches are not successful. CONCLUSIONS: Recommendations from several recent CPGs regarding the assessment and management of LBP were similar. Clinicians who care for patients with LBP should endeavor to adopt these recommendations to improve patient care. Future CPGs may wish to invite coauthors from targeted clinician user groups, increase patient participation, update their literature searches before publication, conduct their own quality assessment of studies, and consider cost-effectiveness and other aspects in their recommendations more explicitly.

Potential triaging of referrals for lumbar spinal surgery consultation: a comparison of referral accuracy from pain specialists, findings from advanced imaging and a 3-item questionnaire.

BACKGROUND: Waiting times to see a spinal surgeon are among the highest in Canada. However, most patients who are referred would not benefit from surgical care. Effective triaging of surgical candidates may reduce morbidity related to prolonged waiting times and optimize use of limited resources. METHODS: We administered a questionnaire consisting of 3 items identifying leg-dominant or back-dominant pain among 119 consecutive patients who presented at a community spinal pain centre or a spinal surgical unit for assessment of an elective lumbar problem. We analyzed the questionnaire under 2 different scenarios: 1 hypothesized to be more sensitive and 1 hypothesized to be more specific. RESULTS: For the "sensitive" scenario of clearly back-dominant pain, the sensitivity of the questionnaire was 100% in identifying appropriate surgical candidates. For the "specific" scenario of leg-dominant pain, the questionnaire had a sensitivity of 83% and specificity of 73% in identifying appropriate surgical candidates, which was significantly superior to findings on computed tomography or magnetic resonance imaging (i.e., presence of neurocompressive lesions). When comparing the accuracy of the questionnaire in identifying appropriate surgical candidates to that of an assessment performed by a pain specialist at an acute spinal pain clinic, we found no statistically significant differences between the 2 methods. CONCLUSION: Use of the questionnaire when triaging patients may decrease the number of unnecessary referrals to spine surgeons. Adopting such a method of triaging could reduce waiting times for appropriate surgical candidates and potentially improve the outcomes of any resulting spinal surgery performed in a timely fashion.

Can cost utility evaluations inform decision making about interventions for low back pain?

BACKGROUND CONTEXT: Low back pain (LBP) is associated with high health-care utilization and lost productivity. Numerous interventions are routinely used, although few are supported by strong evidence. Cost utility analyses (CUAs) may be helpful to inform decision makers. PURPOSE: To conduct a systematic review of CUAs of interventions for LBP. STUDY DESIGN: Systematic review. METHODS: A search strategy combining medical subject headings and free text related to LBP and health economic evaluations was executed in MEDLINE. Cost utility analyses combined with randomized controlled trials for LBP were included. Studies that were published before 1998, non-English, decision analyses, and duplicate reports were excluded. Search results were evaluated by two reviewers, who extracted data independently related to clinical study design, economic study design, direct cost components, utility results, cost results, and CUA results. RESULTS: The search produced 319 citations, and of these 15 met eligibility criteria. Most were from the United Kingdom (n=8), published in the past 3 years (n=12), studied chronic LBP or radiculopathy (n=13), and had a follow-up >12 months (n=13). Combined, there were 33 study groups who received a mean 2.1 interventions, most commonly education (n=17), exercise therapy (n=13), spinal manipulation therapy (n=7), surgery (n=7), and usual care from a general practitioner (n=7). Mean baseline utility was 0.57, improving to 0.67 at follow-up; the mean difference in utility improvement between study groups was 0.04. Based on available data and converted to US dollars, the cost per quality-adjusted life year ranged from $304 to 579,527 dollars, with a median of 13,015 dollars. CONCLUSIONS: Few CUAs were identified for LBP, and there was heterogeneity in the interventions compared, direct cost components measured, indirect costs, other methods, and results. Reporting quality was mixed. Currently published CUAs do not provide sufficient information to assist decision makers. Future CUAs should attempt to measure all known direct cost components relevant to LBP, estimate indirect costs such as lost productivity, have a follow-up period sufficient to capture meaningful changes, and clearly report methods and results to facilitate interpretation and comparison.

The reliability of determining "leg dominant pain".

BACKGROUND CONTEXT: Patients with back dominant pain generally have a worse prognosis after spine surgery when compared with patients with leg dominant pain. Despite the importance of determining whether patients with lumbar spine pain have back or leg dominant pain as a predictor for success after decompression surgery, there are limited data on the reliability of methods for doing so. PURPOSE: To assess the test-retest reliability of a patient's ability to describe whether their lumbar spine pain is leg or back dominant using standardized questions. STUDY DESIGN/SETTING: Prospective, blinded, test-retest cohort study performed in an academic spinal surgery clinic. PATIENT SAMPLE: Consecutive patients presenting for consultation to one of three spinal surgeons for lumbar spine pain were enrolled. OUTCOME MEASURES: Eight questions to ascertain a patient's dominant location of pain, either back dominant or leg dominant, were identified from the literature and local experts. METHODS: These eight questions were administered in a test-retest format over two weeks. The test-retest reliability of these questions were assessed in a self-administered questionnaire format for one group of patients and by a trained interviewer in a second group. RESULTS: The test-retest reliability of each question ranged from substantial (eg, interviewer-administered percent question, weighted kappa=0.77) to slight (eg, self-administered pain diagram, weighted kappa=0.09). The Percent question was the most reliable in both groups (self-administered, interviewer). All questions in the interviewer-administered group were significantly (p<.001) more reliable than the self-administered group. Depending on the question, between 0% and 32% of patients provided a completely opposite response on test-retest. There was variability in prevalence of leg dominant pain, depending on which question was asked and there was no single question that identified all patients with leg dominant pain. CONCLUSION: A patient's ability to identify whether his or her lumbar spine pain is leg or back dominant may be unreliable and depends on which questions are asked, and also how they are asked. The Percent question is the most reliable method to determine the dominant location of pain. However, given the variability of responses and the generally poorer reliability of many specific questions, it is recommended that multiple methods be used to assess a patient's dominant location of pain.

Evidence-informed management of chronic low back pain with lumbar extensor strengthening exercises.

The management of chronic low back pain (CLBP) has proven very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of to The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this supplement were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.

Evidence-informed management of chronic low back pain with medicine-assisted manipulation.

The management of chronic low back pain (CLBP) has proven very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence Informed Management of Chronic Low Back Pain Without Surgery. Articles in this supplement were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.

Evidence-informed management of chronic low back pain with physical activity, smoking cessation, and weight loss.

The management of chronic low back pain (CLBP) has proven to be very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.

Evidence-informed management of chronic low back pain with prolotherapy.

The management of chronic low back pain (CLBP) has proven to be very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.

Evidence-informed management of chronic low back pain with spinal manipulation and mobilization.

The management of chronic low back pain (CLBP) has proven very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.

Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: A survey of practitioners.

OBJECTIVE: To study the side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain. DESIGN: Practitioner postal survey. SETTING: Postal survey of practitioners of prolotherapy for back and neck pain in the United States and Canada. PARTICIPANTS: A sample of prolotherapy practitioners from 2 professional organizations were surveyed about their training and experience, use of specific treatment procedures, estimated prevalence of side effects, and adverse events related to prolotherapy for back and neck pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence of side effects and adverse events. RESULTS: Surveys were completed by 171 practitioners (response rate, 50%). Ninety-eight percent held medical degrees, and 83% were board certified in various disciplines. Respondents had a median of 10 years of experience, during which they had treated a median of 500 patients and given a median of 2000 treatments. Side effects with the highest median estimated prevalence were pain (70%), stiffness (25%), and bruising (5%). There were 472 reports of adverse events, including 69 that required hospitalization and 5 that resulted in permanent injury secondary to nerve injury. The vast majority (80%) were related to needle injuries such as spinal headache (n = 164), pneumothorax (n=123), temporary systemic reactions (n = 73), nerve damage (n = 54), hemorrhage (n = 27), nonsevere spinal cord insult (ie, meningitis, paralysis, spinal cord injury) (n = 9), and disk injury (n = 2). CONCLUSIONS: Side effects related to prolotherapy for back and neck pain, such as temporary postinjection pain, stiffness, and bruising, are common and benign. Adverse events related to prolotherapy for back and neck pain are similar in nature to other widely used spinal injection procedures. Further study is needed to fully describe the adverse event profile of prolotherapy for back and neck pain.