Bone Marrow Concentrate (BMC) Therapy in Musculoskeletal Disorders: Evidence-Based Policy Position Statement of American Society of Interventional Pain Physicians (ASIPP)

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration\u27s (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine. OBJECTIVES: The aim of this review is to describe the current regulatory guidelines set in place by the FDA, specifically the terminology around minimal manipulation and homologous use within Regulation 21 CFR Part 1271, and specifically how this applies to the use of BMC in interventional musculoskeletal medicine. METHODS: The methodology utilized here is similar to the methodology utilized in preparation of multiple guidelines employing the experience of a panel of experts from various medical specialties and subspecialties from differing regions of the world. The collaborators who developed these position statements have submitted their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these position statements. The literature pertaining to BMC, its effectiveness, adverse consequences, FDA regulations, criteria for meeting the standards of minimal manipulation, and homologous use were comprehensively reviewed using a best evidence synthesis of the available and relevant literature. RESULTS/Summary of Evidence: In conjunction with evidence-based medicine principles, the following position statements were developed: Statement 1: Based on a review of the literature in discussing the preparation of BMC using accepted methodologies, there is strong evidence of minimal manipulation in its preparation, and moderate evidence for homologous utility for various musculoskeletal and spinal conditions qualifies for the same surgical exemption. Statement 2: Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions. • The evidence is highest for knee osteoarthritis with level II evidence based on relevant systematic reviews, randomized controlled trials and nonrandomized studies. There is level III evidence for knee cartilage conditions. • Based on the relevant systematic reviews, randomized trials, and nonrandomized studies, the evidence for disc injections is level III. • Based on the available literature without appropriate systematic reviews or randomized controlled trials, the evidence for all other conditions is level IV or limited for BMC injections. Statement 3: Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by trained physicians with the appropriate precautions under image guidance utilizing a sterile technique. Statement 4: Musculoskeletal disorders and spinal disorders with related disability for economic and human toll, despite advancements with a wide array of treatment modalities. Statement 5: The 21st Century Cures Act was enacted in December 2016 with provisions to accelerate the development and translation of promising new therapies into clinical evaluation and use. Statement 6: Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders and spine. With mixed results, these therapies are greatly outpacing the evidence. The reckless publicity with unsubstantiated claims of beneficial outcomes having putative potential, and has led the FDA Federal Trade Commission (FTC) to issue multiple warnings. Thus the US FDA is considering the appropriateness of using various therapies, including BMC, for homologous use. Statement 7: Since the 1980\u27s and the description of mesenchymal stem cells by Caplan et al, (now called medicinal signaling cells), the use of BMC in musculoskeletal and spinal disorders has been increasing in the management of pain and promoting tissue healing. Statement 8: The Public Health Service Act (PHSA) of the FDA requires minimal manipulation under same surgical procedure exemption. Homologous use of BMC in musculoskeletal and spinal disorders is provided by preclinical and clinical evidence. Statement 9: If the FDA does not accept BMC as homologous, then it will require an Investigational New Drug (IND) classification with FDA (351) cellular drug approval for use. Statement 10: This literature review and these position statements establish compliance with the FDA\u27s intent and corroborates its present description of BMC as homologous with same surgical exemption, and exempt from IND, for use of BMC for treatment of musculoskeletal tissues, such as cartilage, bones, ligaments, muscles, tendons, and spinal discs. CONCLUSIONS: Based on the review of all available and pertinent literature, multiple position statements have been developed showing that BMC in musculoskeletal disorders meets the criteria of minimal manipulation and homologous use. KEY WORDS: Cell-based therapies, bone marrow concentrate, mesenchymal stem cells, medicinal signaling cells, Food and Drug Administration, human cells, tissues, and cellular tissue-based products, Public Health Service Act (PHSA), minimal manipulation, homologous use, same surgical procedure exemption

CONTRIBUTION A L'ETUDE DE LA VIGNE DANS LE BEAUJOLAIS

LYON1-BU Santé (693882101) / SudocSudocFranceF

Screening, brief intervention, and referral to treatment (SBIRT) for offenders: protocol for a pragmatic randomized trial

Abstract Background Although screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based technique that, in some health-care settings, has been shown to cost-effectively reduce alcohol and drug use, research on the efficacy of SBIRT among criminal offender populations is limited. Such populations have a high prevalence of drug and alcohol use but limited access to intervention, and many are at risk for post-release relapse and recidivism. Thus, there exists a need for treatment options for drug-involved offenders of varying risk levels to reduce risky behaviors or enter treatment. Methods/design This protocol describes an assessment of SBIRT feasibility and effectiveness in a criminal justice environment. Eight-hundred persons will be recruited from a large metropolitan jail, with the experimental group receiving an intervention depending on risk level and the control group receiving minimal intervention. The intervention will assess the risk level for drug and alcohol misuse by inmates, providing those at low or medium risk a brief intervention in the jail and referring those at high risk to community treatment following release. In addition, a brief treatment (eight-session) option will be available. Using data from a 12-month follow-up interview, the primary study outcomes are a reduction in drug and alcohol use, while secondary outcomes include participation in treatment, rearrest, quality of life, reduction in HIV risk behaviors, and costs of SBIRT. Expected value Individual reductions in alcohol and drug use can have significant effects on public health and safety when observed over a large population at risk for substance-use problems. With wider dissemination statewide or nationwide, a relatively low-cost intervention such as SBIRT could offer demonstrated benefits in this population. Trial registration Clinical Trials Government Identifier, NCT01683643

Adherence to Scheduled Sessions in a Randomized Field Trial of Case Management: The Criminal Justice–Drug Abuse Treatment Studies Transitional Case Management Study

The Transitional Case Management (TCM) study, one of the projects of the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) cooperative, was a multi-site randomized test of whether a strengths-based case management intervention provided during an inmate’s transition from incarceration to the community increases participation in community substance abuse treatment, enhances access to needed social services, and improves drug use and crime outcomes. As in many intervention studies, TCM experienced a relatively large percentage of treatment-group participants who attended few or no scheduled sessions. The paper discusses issues with regard to participation in community case management sessions, examines patterns of session attendance among TCM participants, and analyzes client and case manager characteristics that are associated with number of sessions attended and with patterns of attendance. The average number of sessions (out of 12) attended was 5.7. Few client or case manager characteristics were found to be significantly related to session attendance. Clinical and research implications of the findings and of adherence in case management generally are discussed

Viral gene transfer of APPsα rescues synaptic failure in an Alzheimer’s disease mouse model

International audienc

Does changing antiretroviral therapy in the first trimester for pregnancy-related concerns have an impact on viral suppression ?: Changing ART in pregnancy and viral suppression ?

International audienceOBJECTIVE:To determine whether changing antiretroviral therapy (ART) during pregnancy because of concern about fetal risks led to poorer virological outcomes.METHODS:All pregnancies in women with HIV-1 infection enrolled in the national multicenter prospective French Perinatal cohort at 14 week gestation or more were included between January 2005 and December 2015, if the mother was on ART at conception with a plasma viral load <50 copies/mL. The reasons for a change in the ART were analyzed according to treatment guidelines at the time of the pregnancy and defined as for safety concerns in the absence of reported maternal intolerance. Virological and pregnancy outcomes were studied by survival analysis and logistic regression adjusted for a propensity score established for each patient according to baseline characteristics.RESULTS:Of 7079 pregnancies in the overall cohort, 1797 had ART at conception with a viral load <50 copies/mL before 14 week gestation. Of these, 22 changed regimens in the first trimester for intolerance, and 411 of the remaining 1775 (23%) solely for safety concerns. The proportion of change was higher when the initial treatment was not recommended in the national guidelines (OR adjusted: 23.1 [14.0-38.2]), than when it was an alternative option (ORa: 2.2 [1.3-3.7]), as compared to recommended first-line regimens. Treatment changes for safety concerns did not lead to poorer virological control, compared with pregnancies without such changes (19.3% vs. 15.6%, HRa: 1.0 [0.7-1.4]).CONCLUSIONS:Changing ART early in pregnancy to regimens considered safer for pregnancy, and neonatal health did not have a destabilizing effect on viral suppression