Multidisciplinary Management Strategies for Long COVID: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions.

Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Platelet Rich Plasma and Platelet-Related Products in the Treatment of Radiculopathy-A Systematic Review of the Literature.

Back pain with radicular symptoms is associated with detrimental physical and emotional functioning and economic burden. Conservative treatments including physical, pharmacologic and injection therapy may not provide clinically significant or long-standing relief. Regenerative medicine research including Platelet rich plasma (PRP), Platelet lysate (PL) or Plasma rich in growth factors (PRGF) continues to develop, however evidence appraisal for treatment of radicular pain remains lacking. Thus, we performed a systematic review to evaluate the effectiveness of epidural steroid injections containing PRP or related products to treat radicular pain. Embase, PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were queried. Twelve studies were included in qualitative analysis, consisting of three randomized controlled trials and nine observational studies. The primary outcome was pain intensity, and secondary outcomes included functional improvement, anatomical changes on advanced imaging, and adverse events. All studies identified improved pain intensity and functional outcomes after epidural injection of PRP, PRGF and/or PL. Similar or longer lasting pain relief was noted in the PRP cohort compared to the cohort receiving epidural steroid injections with effects lasting up to 12-24 months. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis revealed a very-low certainty of evidence due to risk of bias, indirectness, and imprecision.

SPECT-CT as a Predictor of Pain Generators in Patients Undergoing Intra-Articular Injections for Chronic Neck and Back Pain.

BACKGROUND: The ability to accurately predict pain generators for chronic neck and back pain remains elusive. OBJECTIVE: We evaluated whether injections targeted at foci with uptake on single-photon emission computerized tomography-computed tomography (SPECT-CT) were associated with improved outcomes in patients with chronic neck and back pain. METHODS: A retrospective review was completed on patients undergoing SPECT-CT for chronic neck and back pain between 2016 and 2020 at a tertiary academic center. Patients' records were reviewed for demographic, clinical, imaging, and outcomes data. Only those patients who had facet injections after SPECT-CT were included in this evaluation. Patients undergoing injections targeted at foci of abnormal radiotracer uptake were compared with patients without uptake concerning immediate positive response, visual analog scale, and the need for additional injection or surgery at the target level. RESULTS: A total of 2849 patients were evaluated with a SPECT-CT for chronic neck and back pain. Of those, 340 (11.9%) patients received facet joint injections after SPECT-CT. A propensity score regression analysis adjusted for age, gender, body mass index, hypertension, multiple target injections, and injection location showed uptake targeted injections not being associated with an improved immediate positive response (odds ratio: 0.64; 95% confidence interval: 0.34-1.21; P = 0.172). In patients with a failed facet injection preceding SPECT-CT, adding SPECT-CT to guide facet injections was associated with a decrease in visual analog scale pain scores 2 weeks after injection (P = 0.018), particularly when changes were made to the facets being targeted (P = 0.010). CONCLUSION: This study suggests that there is benefit with SPECT-CT specially to guide facet injections after failed prior facet injections.

Efficacy and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I  2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I  2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.

Injectable Biologics for Neuropathic Pain: A Systematic Review.

BACKGROUND: Neuropathic pain is a complex condition that can be refractory to conventional management and can cause persistent suffering in patients. Current pharmacologic treatments can provide temporary symptomatic relief; however, the mechanism of these therapies does not address the underlying cause of neuropathic pain. The use of injectable biologics for neuropathic pain has multiple proposed mechanisms for analgesia including attenuation of inflammatory mediated processes, arrest or delay of the degenerative process, inhibition of apoptotic pathways, and augmentation of the survival and recovery of injured and uninjured nerves. STUDY DESIGN: A systematic review of human studies involving the use of injectable biologics for neuropathic pain. METHODS: A comprehensive search of several data bases including Ovid MEDLINE ® and Epub Ahead of Print, In Process & Other Non-Indexed Citations and Daily, and Ovid Embase from inception to November 24, 2020. RESULTS: The initial search yielded 3,450 studies with an additional 6 studies identified through other resources. Twenty-seven studies were included after independent review by two of the investigators. The included studies assessed the efficacy of injectable biologics for the treatment of neuropathic pain defined as pain reduction. Secondary outcome measures included functional improvement as well as safety of the procedures. A qualitative assessment of the literature without meta-analysis was performed due to the heterogeneity of the data. CONCLUSION: According to the GRADE criteria, there is very low certainty of evidence in support of the efficacy of injectable biologics for treatment of neuropathic pain. Future efforts should focus on creating a standardized methodology and study design with respect to preparation, dosage and route of administration of biologics. This will serve as a catalyst for higher quality randomized trials with generation of more useful data to help drive informed clinical decision making.

Autologous Platelet-Rich Plasma Applications in Chronic Pain Medicine: Establishing a Framework for Future Research - A Narrative Review.

BACKGROUND: During the last decades, platelet-rich plasma has been studied for the treatment of multiple chronic pain conditions, in addition to being employed in the enhancement of healing after tissue injury. OBJECTIVE: To establish a framework for future research regarding the utilization of platelet-rich plasma in the treatment of chronic tissue injuries. METHODS: Preclinical and clinical studies from 2000-2020 relevant to applications of platelet-rich plasma for the treatment of chronic pain conditions were extracted from PubMed and Medline databases. The studies were analyzed on the basis of the study population, type of intervention, method of platelet-rich plasma preparation, the number of treatments administered, the timeframe of injections, and clinical outcomes. RESULTS: Although several preclinical studies and double-blind, randomized trials have shown promising results in the application of platelet-rich plasma for the treatment of multiple chronic pain conditions, various studies have also reported controversial results. Additionally, the methods employed for obtaining the platelet-rich plasma have not been standardized between studies, resulting in different concentrations of blood components between the preparations utilized. Moreover, differences between studies were also found regarding the number of injections administered per treatment. CONCLUSIONS: Future research addressing the utilization of platelet-rich plasma in the treatment of chronic pain conditions should focus on shedding light on the following major questions: a) Is there a dose-effect relation between the platelet count and the clinical efficacy of the preparation?; b) What pathology determinants should be considered when selecting between leukocyte-enriched and leukocyte-depleted concentrates?; c) What is the role of platelet activation methods on the clinical efficacy of platelet-rich plasma?; d) Is there an optimal number of injections and time frame for application of multiple injection treatment cycles?; e) Does the addition of local anesthetics affect the clinical efficacy of platelet-rich plasma?; and f) Is there potential for future platelet-rich plasma applications for the treatment of neuropathic pain of peripheral origin?

Time-to-enrollment in clinical trials investigating neurological recovery in chronic spinal cord injury: observations from a systematic review and ClinicalTrials.gov database.

Currently, large numbers of clinical trials are performed to investigate different forms of experimental therapy for patients suffering from chronic spinal cord injury (SCI). However, for the enrollment process, there are different views on how the time period between injury and interventions should be determined. Herein, we sought to evaluate the impact of time-to-enrollment in chronic SCI clinical trials. A data set comprising 957 clinical studies from clinicalTrials.gov was downloaded and analyzed focusing on the eligibility criteria for post-injury time-to-enrollment. We also aggregated individual patient data from nine clinical trials of regenerative interventions for chronic SCI selected by a systematic literature search from 1990 to 2018. Characteristics of the studies were assessed and compared by dividing into three groups based on time-to-enrollment (group 1 ≤ 12 months, group 2 = 12-23 months and group 3 ≥ 24 months). In ClinicalTrials.gov registry, 445 trials were identified for chronic SCI where 87% (385) were unrestricted in the maximum post-injury time for trial eligibility. From systematic literature search, nine studies and 156 patients (group 1 = 30, group 2 = 55 and group 3 = 71) were included. The range of time-to-enrollment was 0.5 to 321 months in those studies. We also observed various degrees of motor and sensory improvement in between three time-to-enrollment groups. Our results indicate that enrolling wide ranges of time-to-enrollment in a group may present imprecise outcomes. Clinical trial designs should consider appropriate post-injury time frames to evaluate therapeutic benefit.

The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review.

BACKGROUND CONTEXT: There are limited treatments for discogenic low back pain. Intradiscal injections of biologic agents such as platelet-rich plasma (PRP) or stem cells (SC) are theorized to have regenerative properties and have gained increasing interest as a possible treatment, but the evidence supporting their use in clinical practice is not yet well-defined. PURPOSE: Determine the effectiveness of intradiscal biologics for treating discogenic low back pain. STUDY DESIGN: PRISMA-compliant systematic review. PATIENT SAMPLE: Patients with discogenic low back pain confirmed by provocation discography or clinical and imaging findings consistent with discogenic pain. OUTCOME MEASURES: The primary outcome was the proportion of individuals with ≥50% pain relief after intradiscal biologic injection at 6 months. Secondary outcomes included ≥2-point pain score reduction on NRS; patient satisfaction; functional improvement; decreased use of other health care, including analgesics and surgery; and structural disc changes on MRI. METHODS: Comprehensive literature search performed in 2018 and updated in 2020. Interventions included were biologic therapies including mesenchymal stem cells, platelet rich plasma, microfragmented fat, amniotic membrane-based injectates, and autologous conditioned serum. Any other treatment (sham or active) was considered for comparative studies. Studies were independently reviewed. RESULTS: The literature search yielded 3,063 results, 37 studies were identified for full-text review, and 12 met established inclusion criteria for review. The quality of evidence on effectiveness of intradiscal biologics was very low. A single randomized controlled trial evaluating platelet-rich plasma reported positive outcomes but had significant methodological flaws. A single trial that evaluated mesenchymal stem cells was negative. Success rates for platelet-rich plasma injectate in aggregate were 54.8% (95% Confidence Interval: 40%-70%). For mesenchymal stem cells, the aggregate success rate at six months was 53.5% (95% Confidence Interval: 38.6%-68.4%), though using worst-case analysis this decreased to 40.7% (95% Confidence Interval: 28.1%-53.2%). Similarly, ≥30% functional improvement was achieved in 74.3% (95% Confidence Interval: 59.8%-88.7%) at six months but using worst-case analysis, this decreased to 44.1% (95% Confidence Interval: 28.1%-53.2%). CONCLUSION: Limited observational data support the use of intradiscal biologic agents for the treatment of discogenic low back pain. According to the Grades of Recommendation, Assessment, Development and Evaluation System, the evidence supporting use of intradiscal mesenchymal stem cells and platelet-rich plasma is very low quality.

Characteristics of completed clinical trials for spinal cord injury from 1999 to 2020.

Numerous clinical trials are being conducted in the field of spinal cord injury (SCI). These trials are typically registered on ClinicalTrials.gov. The objective of this study was to identify the characteristics of the completed SCI trials and characterize the potential factors associated with publication. ClinicalTrials.gov database was queried for all the completed trials on patients with SCI. Baseline characteristics of the completed trials were assessed. The publication status of these trials was identified using PubMed or Google Scholar. The secondary and primary outcomes reported in the publication were then compared to the outcomes registered in ClinicalTrial.gov. Multivariable logistic regression analysis was performed to determine the characteristics associated with publication status and time to publication. A total of 457 of 1,061 trials on SCI were completed. Of those, 60% were ultimately published. Trials that had received funding from sources besides the NIH, private industries, or the federal government were more likely to remain unpublished. The median time to publish was three years, with larger trials taking a longer time. The median sample size for completed trials was 30. Assessment of mismatch rates in primary outcomes of published data to registered outcomes was 8.9%. In SCI trials, outcomes registered on ClinicalTrial.gov often matched published results. Additionally, sample size and funding source play a significant role in the publication rate of these trials. Published data represents a reliable source for clinicians, researchers, and patients; efforts to curb publication bias and reporting bias are paramount for implementing evidence-based practices and ensure proper scientific conduct.

Outcomes of a Comprehensive Pain Rehabilitation Program for Patients With Fibromyalgia.

OBJECTIVE: To analyze opioid intake interference with psychological, well-being, and functional outcomes and medication tapering in patients with fibromyalgia admitted to the Mayo Clinic Pain Rehabilitation Program (MCPRP) in Florida. PATIENTS AND METHODS: A retrospective study on MCPRP outcomes was conducted. We reviewed the health records of 150 patients with fibromyalgia who participated in the program from May 1, 2014, to May 1, 2015. All patients were asked to fill out a survey at admission to and dismissal from the program. Surveys contained questions from the numeric pain score, Multidimensional Pain Inventory (perceived life control and interference of pain subscales), Center for Epidemiological Studies-Depression Scale, Pain Catastrophizing Scale, 36-Item Short-Form Health Status Survey (general health perceptions subscale), and Pain Self-Efficacy Questionnaire. A medical record review identified categories and number of medications at program admission and dismissal. Patients were divided in 2 groups: those whose concomitant medication did not include opioids at admission (no opioids group) and those whose concomitant medication included opioids at admission (opioids group). RESULTS: By dismissal from the MCPRP, patients with fibromyalgia in the no opioids group had a significant (P<.05) improvement in all the self-reported scores. Medication, including opioids, were effectively tapered at a substantially higher percentage in the opioids group. CONCLUSION: Benefit of the comprehensive pain rehabilitation program in patients with fibromyalgia was indicated by clinical improvements in pain severity, physical and emotional health, and functional capacity while successfully tapering medication. Opioid intake at admission may modify the program outcomes.

The Effectiveness and Safety of Platelet-Rich Plasma for Chronic Wounds: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers. PATIENTS AND METHODS: We searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers. RESULTS: We included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events. CONCLUSION: Autologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020172817.

A three-dimensional computed tomography study to determine the ideal method for fluoroscopically-guided bone marrow aspiration from the iliac crest.

Bone marrow aspiration (BMA) through the iliac crest is potentially unsafe due to the vicinity of neurovascular structures in the greater sciatic notch. Our objective was to investigate the safety of a recently described BMA technique, specifically a trajectory from the posterior superior iliac spine (PSIS) to the anterior inferior iliac spine (AIIS). We conducted a chart review of 260 patients, analyzing three-dimensional reconstructed computed tomography images of the pelvis and sacrum to validate that this new approach offers a wide safety margin from the greater sciatic notch. Analysis of three-dimensional computed tomography scans demonstrated that the PSIS to AIIS trajectory never crossed the greater sciatic notch. The trajectory was noted to be at least one cm away from the greater sciatic notch in all measurements. The new trajectory entered the PSIS at 25.29 ± 4.34° (left side) and 24.93 ± 4.15° (right side) cephalad from the transverse plane, and 24.58 ± 4.99° (left side) and 24.56 ± 4.67° (right side) lateral from the mid-sagittal plane. The area of bone marrow encountered with the new approach was approximately 22.5 cm2. Utilizing the same CT scans, the trajectory from the traditional approach crossed the greater sciatic notch in all scans, highlighting the potential for violating the greater sciatic notch boundary and damaging important neurovascular structures. Statistically significant sex-related differences were identified in needle trajectory angles for both approaches. We conclude that based on this three-dimensional computed tomography study, a trajectory from the PSIS to the AIIS for BMA may offer a wide safety margin from the greater sciatic notch.

Promising role for mesenchymal stromal cells in coronavirus infectious disease-19 (COVID-19)-related severe acute respiratory syndrome?

Mesenchymal stromal cells (MSC) have immune regulatory and tissue regenerative properties. MSCs are being studied as a therapy option for many inflammatory and immune disorders and are approved to treat acute graft-versus-host disease (GvHD). The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic and associated coronavirus infectious disease-19 (COVID-19) has claimed many lives. Innovative therapies are needed. Preliminary data using MSCs in the setting of acute respiratory distress syndrome (ARDS) in COVID-19 are emerging. We review mechanisms of action of MSCs in inflammatory and immune conditions and discuss a potential role in persons with COVID-19.

Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice.

Microglia play an important role in the central sensitization and chronic pain. However, a direct connection between microglial function and pain development in vivo remains incompletely understood. To address this issue, we applied chemogenetic approach by using CX3CR1creER/+:R26LSL-hM4Di/+ transgenic mice to enable expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi DREADD) in microglia. We found that microglial Gi DREADD activation inhibited spinal nerve transection (SNT)-induced microglial reactivity as well as chronic pain in both male and female mice. Gi DREADD activation downregulated the transcription factor interferon regulatory factor 8 (IRF8) and its downstream target pro-inflammatory cytokine interleukin 1 beta (IL-1ß). Using in vivo spinal cord recording, we found that activation of microglial Gi DREADD attenuated synaptic transmission following SNT. Our results demonstrate that microglial Gi DREADD reduces neuroinflammation, synaptic function and neuropathic pain after SNT. Thus, chemogenetic approaches provide a potential opportunity for interrogating microglial function and neuropathic pain treatment.

Differences in Cytotoxicity of Lidocaine, Ropivacaine, and Bupivacaine on the Viability and Metabolic Activity of Human Adipose-Derived Mesenchymal Stem Cells.

PURPOSE: We evaluated biological effects of distinct local anesthetics on human adipose-derived mesenchymal stem cells when applied to reduce periprocedural pain during mesenchymal stem cell injections. METHODS AND MATERIALS: Metabolic activity (MTS assay), viability (Live/Dead stain), and gene expression (quantitative real-time reverse-transcriptase polymerase chain reaction) were measured in mesenchymal stem cells incubated with various concentrations of lidocaine, ropivacaine, or bupivacaine during a 12-hr time course. RESULTS: Cell viability and metabolic activity decreased in a dose, time, and substance-specific manner after exposure to lidocaine, ropivacaine, and bupivacaine, with ropivacaine being the least cytotoxic. Cell viability decreases after brief exposure (<1.5 hrs) at clinically relevant concentrations (eg, 8 mg/ml of lidocaine, 2.5 mg/ml of ropivacaine or bupivacaine). Mesenchymal stem cells exposed to local anesthetics change their expression of mRNA biomarkers for stress response (EGR1, EGR2), proliferation (MKI67, HIST2H4A), ECM (COL1A1, COL3A1), and cell surface marker (CD105). CONCLUSIONS: Local anesthetics are cytotoxic to clinical-grade human mesenchymal stem cells in a dose-, time-, and agent-dependent manner and change expression of ECM, proliferation, and cell surface markers. Lidocaine and bupivacaine are more cytotoxic than ropivacaine. Single-dose injections of local anesthetics may affect the biological properties of mesenchymal stem cells in vitro but may not affect the effective dose of MSCs in a clinical setting.

Sex-Related Differences in Symptoms and Psychosocial Outcomes in Patients With Fibromyalgia: A Prospective Questionnaire Study.

OBJECTIVE: To investigate sex-related differences in patients with fibromyalgia (FM) in terms of demographic characteristics and clinical features, including tender point count (TPC), mood disorders, sleep problems, FM symptom severity, fatigue, cognitive dysfunction, and quality of life (QOL). PATIENTS AND METHODS: We studied 668 consecutive patients with FM (606 women) from May 1, 2012, to November 30, 2013. Validated questionnaires assessed outcomes of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), sleep problems (Medical Outcomes Study Sleep Scale), FM symptom severity (Revised Fibromyalgia Impact Questionnaire), fatigue (Multidimensional Fatigue Inventory), cognitive dysfunction (Multiple Ability Self-report Questionnaire), and QOL (36-Item Short Form Health Survey). Nonparametric Mann-Whitney U and Pearson χ2 tests were used to compare continuous and categorical outcome measures, respectively, between men and women. Linear regression models were performed for all continuous dependent variables, adjusting for age, body mass index, ethnicity, marital status, and highest education level completed. P<.05 was considered statistically significant. The Benjamini-Hochberg procedure was used to adjust for multiple comparisons. RESULTS: Multiple linear regression analysis revealed a significant association of female sex and greater TPC (P<.001), lower overall FM symptom severity (lower overall Revised Fibromyalgia Impact Questionnaire score; P=.03), and higher QOL subscale score for vitality (36-Item Short Form Health Survey vitality subscale score; P=.02). After adjustment for multiple comparisons, only the association between female sex and greater TPC remained significant. There were no sex-related differences in demographic characteristics, depression, anxiety, sleep problems, FM symptom severity, cognitive dysfunction, and QOL. CONCLUSION: A higher TPC may be associated with female sex in patients with FM. The assumption of other sex-based differences in the clinical presentation of FM was not supported in our study.

A Systematic Review of Intra-Articular Ketamine for Postoperative Analgesia.

BACKGROUND: This systematic review appraises the evidence from human clinical trials comparing postoperative pain scores and opioid consumption in patients receiving intra-articular ketamine versus other modalities of analgesia after orthopedic joint procedures. METHODS: Studies were identified from Embase, Scopus, and OVID Medline databases. Included studies compared patients receiving intra-articular ketamine versus other modalities of analgesia. The primary outcome of interest was postprocedural pain score and total opioid consumption, whereas secondary outcomes included time to rescue analgesic medication request, active range of motion, time to mobilization, and adverse effects. RESULTS: Seventeen studies were included. Dosage of ketamine varied widely from 0.25 to 2 mg/kg. Fifteen of 17 demonstrated decreased overall pain scores and decreased total postoperative opioid consumption in patients receiving intra-articular ketamine versus control groups. Included studies generally demonstrated reduced time to mobilization and increased latency until rescue analgesic medication in the intra-articular ketamine group. CONCLUSIONS: Patients who received intra-articular ketamine generally reported lower pain scores and had lower postoperative opioid consumption after orthopedic joint procedures. This suggests that the intra-articular route of ketamine delivery may be a useful analgesic modality, although future larger-scale trials should explore its pharmacokinetics, optimal dosing, safety, and cost-effectiveness.

Factors Associated with Higher Rates of Heterotopic Ossification after Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Heterotopic Ossification (HO) refers to the formation of bone within soft tissue. Traumatic spinal cord injury (SCI) has been shown to be associated with development of HO. However, risk factors for HO following SCI are unknown. In light of this knowledge gap, we performed a systematic review and meta-analysis to summarize available evidence and elucidate risk factors associated with heterotopic ossification. An electronic literature search was conducted using five databases. Studies containing SCI patients, with a proportion diagnosed with HO, were included. Meta-analyses were performed to assess the association between following risk factors and development of HO: sex, type of injury, spasticity, pressure ulcer, injury level, urinary tract infection (UTI), deep vein thrombosis (DVT), number of smokers, and pneumonia. Nine studies with 2,115 patients were included. It was found that males (Odds Ratio [95% Confidence Interval]: 2.25 [1.61, 3.13]), smokers (2.88 [1.62, 5.11]), patients with complete injury (3.61 [2.29, 5.71]), pneumonia (2.86 [2.18, 3.75]), pressure ulcers (2.45 [1.89, 3.18]), UTI (3.84 [2.63, 5.62]) and spasticity (2.12 [1.67, 2.68]) had significantly higher odds of developing HO after spinal cord injury. In contrast, location of injury (Cervical vs. thoracic injury; (1.03 [0.72, 1.49]) and DVT (1.37 [0.91, 2.07]) were not associated with development of HO. Pooled results from existing literature on HO development show that several factors are significantly associated with development of HO. Given the complexity of SCI management, the results might have a positive impact on the clinical practice by leading to an effective screening aproach.