Is Epidural Injection of Sodium Chloride Solution a True Placebo or an Active Control Agent? A Systematic Review and Meta-Analysis.

BACKGROUND: Epidural injections have been extensively used since their description in 1901, and steroids since their first utilization in 1952. Multiple randomized controlled trials and systematic reviews have reached discordant conclusions regarding the effectiveness of sodium chloride solution and steroids in managing spinal pain. True placebo-controlled trials with the injection of an inactive substance to unrelated structures have been nonexistent. Consequently, the discussions continue to escalate, seemingly without proper discourse. In this review, we sought to assess the true placebo nature of saline and the effectiveness of steroids. OBJECTIVES: This assessment of sodium chloride solution is undertaken to assess if it is a true placebo when injected into the epidural space, is effective alone, and whether steroids are effective when injected with sodium chloride solution rather than local anesthetic in managing spinal pain. STUDY DESIGN: A systematic review of randomized controlled trials utilizing sodium chloride solution alone, steroids alone, or sodium chloride solution with steroids in managing spinal pain secondary to disc herniation or spinal stenosis. METHODS: The systematic review was performed utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Cochrane review criteria and Interventional Pain Management techniques--Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) was used to assess the methodological quality assessment. Qualitative analysis was performed by utilizing best evidence synthesis principles, and quantitative analysis was performed utilizing meta-analysis with conventional methodology and single-arm meta-analysis. PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1966 through December 2018. The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. Outcome measures for the present analysis, 20% improvement from the baseline pain scores or disability scores was considered clinically significant. Effectiveness was determined short-term if it was less than 6 months, whereas longer than 6 months was considered to be long-term. RESULTS: Of the 8 trials meeting inclusion criteria, 2 trials utilized fluoroscopic imaging and one study utilized ultrasound. All other studies performed the procedure without fluoroscopy. With dual-arm meta-analysis, there was no significant difference between epidural sodium chloride solution and epidural steroids with sodium chloride solution. Utilizing single-arm analysis, both epidural saline and epidural steroids with saline were effective in reducing 20% of pain, however, only reducing disability scores by 10% to 12%. Based on the qualitative analysis, epidural saline and epidural steroids with saline showed effect beyond placebo and showed level I, or strong evidence, that neither epidural saline, nor epidural steroids with saline are placebo and that both are effective. LIMITATIONS: Despite 8 randomized controlled trials, only 2 of them utilized fluoroscopy. Overall evidence is considered less than optimal and further studies elucidating these actions are strongly recommended. CONCLUSIONS: The findings of this systematic review and meta-analysis show that epidurally administered sodium chloride solution and sodium chloride solution with steroids may be effective in managing low back and lower extremity pain. Consequently, the findings of this review provide information that epidurally administered sodium chloride solution is not a true placebo.

Utilization of Vertebral Augmentation Procedures in the USA: a Comparative Analysis in Medicare Fee-for-Service Population Pre- and Post-2009 Trials.

PURPOSE OF REVIEW: To review the utilization patterns of vertebral augmentation procedures in the US Medicare population from 2004 to 2017 surrounding concurrent developments in the literature and the enactment of the Affordable Care Act (ACA). RECENT FINDINGS: The analysis of vertebroplasty and kyphoplasty utilization patterns was carried out using specialty utilization data from the Centers for Medicare and Medicaid Services Database. Of note, over the period of time between 2009 and 2017, the number of people aged 65 or older showed a 3.2% rate of annual increase, and the number of Medicare beneficiaries increased by 27.6% with a 3.1% rate of annual increase. Concurrently, vertebroplasty utilization decreased 72.8% (annual decline of 15% per 100,000 Medicare beneficiaries), and balloon kyphoplasty utilization decreased 19% (annual decline of 2.6% per 100,000 Medicare beneficiaries). This translates to a 38.3% decrease in vertebroplasty and balloon kyphoplasty utilization (annual decline of 5.9% per 100,000 Medicare beneficiaries) from 2009 to 2017. By contrast, from 2004 to 2009, there was a total 188% increase in vertebroplasty and balloon kyphoplasty utilization (annual increase rate of 23.6% per 100,000 Medicare beneficiaries). The majority of vertebroplasty procedures were done by radiologists, and the majority of kyphoplasties were done by aggregate groups of spine surgeons. These results illustrate a significant decline in vertebral augmentation procedures in the fee-for-service Medicare population between 2004 and 2017, with dramatic decreases following the publication of two 2009 trials that failed to demonstrate benefit of vertebroplasty over sham and the enactment of the ACA.

Cryptococcal Meningoencephalitis 10 Years After Bone Marrow Transplant in a Patient With Multiple Myeloma.

Cryptococcosis is a fungal infection that mostly affects immunocompromised patients. Diagnosis is based on the detection of cryptococcal antigen in the cerebrospinal fluid (CSF) or serum. Antifungal resistance is emerging, making treatment difficult and long. We report a case of cryptococcosis in a patient with multiple myeloma, years after undergoing a bone marrow transplant. Symptoms were mild, and imaging studies were nonspecific. CSF analysis revealed positive cryptococcal antigen. The patient was started on the standard three-phase antifungal therapy and recovered.

Responsible, Safe, and Effective Use of Biologics in the Management of Low Back Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public presentation and promises as well as in its use. OBJECTIVE: To provide guidance for the responsible, safe, and effective use of biologic therapy in the lumbar spine. To present a template on which to build standardized therapies using biologics. To ground potential administrators of biologics in the knowledge of the current outcome statistics and to stimulate those interested in providing biologic therapy to participate in high quality research that will ultimately promote and further advance this area of medicine. METHODS: The methodology used has included the development of objectives and key questions. A panel of experts from various medical specialties and subspecialties as well as differing regions collaborated in the formation of these guidelines and submitted (if any) their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these guidelines. The literature pertaining to regenerative medicine, its effectiveness, and adverse consequences was thoroughly reviewed using a best evidence synthesis of the available literature. The grading for recommendation was provided as described by the Agency for Healthcare Research and Quality (AHRQ). SUMMARY OF EVIDENCE: Lumbar Disc Injections: Based on the available evidence regarding the use of platelet-rich plasma (PRP), including one high-quality randomized controlled trial (RCT), multiple moderate-quality observational studies, a single-arm meta-analysis and evidence from a systematic review, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best-evidence synthesis. Based on the available evidence regarding the use of medicinal signaling/ mesenchymal stem cell (MSCs) with a high-quality RCT, multiple moderate-quality observational studies, a single-arm meta-analysis, and 2 systematic reviews, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Epidural Injections Based on one high-quality RCT, multiple relevant moderate-quality observational studies and a single-arm meta-analysis, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Facet Joint Injections Based on one high-quality RCT and 2 moderate-quality observational studies, the qualitative evidence for facet joint injections with PRP has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Sacroiliac Joint Injection Based on one high-quality RCT, one moderate-quality observational study, and one low-quality case report, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. CONCLUSION: Based on the evidence synthesis summarized above, there is Level III evidence for intradiscal injections of PRP and MSCs, whereas the evidence is considered Level IV for lumbar facet joint, lumbar epidural, and sacroiliac joint injections of PRP, (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis.Regenerative therapy should be provided to patients following diagnostic evidence of a need for biologic therapy, following a thorough discussion of the patient's needs and expectations, after properly educating the patient on the use and administration of biologics and in full light of the patient's medical history. Regenerative therapy may be provided independently or in conjunction with other modalities of treatment including a structured exercise program, physical therapy, behavioral therapy, and along with the appropriate conventional medical therapy as necessary. Appropriate precautions should be taken into consideration and followed prior to performing biologic therapy. Multiple guidelines from the Food and Drug Administration (FDA), potential limitations in the use of biologic therapy and the appropriate requirements for compliance with the FDA have been detailed in these guidelines. KEY WORDS: Regenerative medicine, platelet-rich plasma, medicinal signaling cells, mesenchymal stem cells, stromal vascular fraction, bone marrow concentrate, chronic low back pain, discogenic pain, facet joint pain, Food and Drug Administration, minimal manipulation, evidence synthesis.

Do Regenerative Medicine Therapies Provide Long-Term Relief in Chronic Low Back Pain: A Systematic Review and Metaanalysis.

BACKGROUND: Several cell-based therapies have been proposed in recent years the management of low back pain, including the injection of medicinal signaling cells or mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). However, there is only emerging clinical evidence to support their use at this time. OBJECTIVE: To assess the effectiveness of MSCs or PRP injections in the treatment of low back and lower extremity pain. STUDY DESIGN: A systematic review and metaanalysis of the effectiveness of PRP and MSCs injections in managing low back and lower extremity pain. DATA SOURCES: PubMed, Cochrane Library, US National Guideline Clearinghouse, prior systematic reviews, and reference lists. The literature search was performed from 1966 through June 2018. STUDY SELECTION: Randomized trials, observational studies, and case reports of injections of biologics into the disc, epidural space, facet joints, or sacroiliac joints. DATA EXTRACTION: Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR). The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. DATA SYNTHESIS: Twenty-one injection studies met inclusion criteria. There were 12 lumbar disc injections, 5 epidural, 3 lumbar facet joint, and 3 sacroiliac joint studies RESULTS: Evidence synthesis based on a single-arm metaanalysis, randomized controlled trials (RCTs), and observational studies, disc injections of PRP and MSCs showed Level 3 evidence (on a scale of Level I through V). Evidence for epidural injections based on single-arm metaanalysis, a single randomized controlled trial and other available studies demonstrated Level 4 (on a scale of Level I through V) evidence. Similarly, evidence for lumbar facet joint injections and sacroiliac joint injections without metaanalysis demonstrated Level 4 evidence (on a scale of Level I through V). LIMITATIONS: Lack of high quality RCTs. CONCLUSION: The findings of this systematic review and single-arm metaanalysis shows that MSCs and PRP may be effective in managing discogenic low back pain, radicular pain, facet joint pain, and sacroiliac joint pain, with variable levels of evidence in favor of these techniques. KEY WORDS: Chronic low back pain, regenerative therapy, medicinal signaling or mesenchymal stem cells, platelet-rich plasma, disc injection, lumbar facet joint injections, sacroiliac joint injections.

Reframing the Prevention Strategies of the Opioid Crisis: Focusing on Prescription Opioids, Fentanyl, and Heroin Epidemic.

The opioid epidemic has been called the "most consequential preventable public health problem in the United States." Though there is wide recognition of the role of prescription opioids in the epidemic, evidence has shown that heroin and synthetic opioids contribute to the majority of opioid overdose deaths. It is essential to reframe the preventive strategies in place against the opioid crisis with attention to factors surrounding the illicit use of fentanyl and heroin. Data on opioid overdose deaths shows 42,000 deaths in 2016. Of these, synthetic opioids other than methadone were responsible for over 20,000, heroin for over 15,000, and natural and semi-synthetic opioids other than methadone responsible for over 14,000. Fentanyl deaths increased 520% from 2009 to 2016 (increased by 87.7% annually between 2013 and 2016), and heroin deaths increased 533% from 2000 to 2016. Prescription opioid deaths increased by 18% overall between 2009 and 2016. The Drug Enforcement Administration (DEA) mandated reductions in opioid production by 25% in 2017 and 20% in 2018. The number of prescriptions for opioids declined significantly from 252 million in 2013 to 196 million in 2017 (9% annual decline over this period), falling below the number of prescriptions in 2006. In addition, data from 2017 shows significant reductions in the milligram equivalence of morphine by 12.2% and in the number of patients receiving high dose opioids by 16.1%. This manuscript describes the escalation of opioid use in the United States, discussing the roles played by drug manufacturers and distributors, liberalization by the DEA, the Food and Drug Administration (FDA), licensure boards and legislatures, poor science, and misuse of evidence-based medicine. Moreover, we describe how the influence of pharma, improper advocacy by physician groups, and the promotion of literature considered peer-reviewed led to the explosive use of illicit drugs arising from the issues surrounding prescription opioids.This manuscript describes a 3-tier approach presented to Congress. Tier 1 includes an aggressive education campaign geared toward the public, physicians, and patients. Tier 2 includes facilitation of easier access to non-opioid techniques and the establishment of a National All Schedules Prescription Electronic Reporting Act (NASPER). Finally, Tier 3 focuses on making buprenorphine more available for chronic pain management as well as for medication-assisted treatment. KEY WORDS: Opioid epidemic, fentanyl and heroin epidemic, prescription opioids, National All Schedules Prescription Electronic Reporting Act (NASPER), Prescription Drug Monitoring Programs (PDMPs).