Response to "Scrutinizing the causal link between excited delirium syndrome and restraint - a commentary on: 'The role of restraint in fatal excited delirium: a research synthesis and pooled analysis' by E.M.F. Strömmer, W. Leith, M.P. Zeegers and M.D. Freeman".

de Boer et al. criticize the conclusions in our 2020 paper on the validity of Excited Delirium Syndrome (ExDS) as "egregiously misleading." Our conclusion was that there "is no existing evidence that indicates that ExDS is inherently lethal in the absence of aggressive restraint." The basis for de Boer and colleague's criticism of our paper is that the ExDS literature does not provide an unbiased view of the lethality of the condition, and therefore the true epidemiologic features of ExDS cannot be determined from what has been published. The criticism is unrelated to the goals or methods of the study, however. Our stated purpose was to investigate "how the term ExDS has evolved in the literature and been endowed with a uniquely lethal quality," and whether there is "evidence for ExDS as a unique cause of a death that would have occurred regardless of restraint, or a label used when a restrained and agitated person dies, and which erroneously directs attention away from the role of restraint in explaining the death." We cannot fathom how de Boer et al. missed this clearly stated description of the study rationale, or why they would endorse a series of fallacious and meaningless claims that gave the appearance that they failed to grasp the basic design of the study. We do acknowledge and thank these authors for pointing out 3 minor citation errors and an equally minor table formatting error (neither of which altered the reported results and conclusions in the slightest), however.

The role of restraint in fatal excited delirium: a research synthesis and pooled analysis.

The purpose of the present study was to perform a comprehensive scientific literature review and pooled data risk factor analysis of excited delirium syndrome (ExDS) and agitated delirium (AgDS). All cases of ExDS or AgDS described individually in the literature published before April 23, 2020 were used to create a database of cases, including demographics, use of force, drug intoxication, mental illness, and survival outcome. Odds ratios were used to quantify the association between death and diagnosis (ExDS vs. AgDS) across the covariates. There were 61 articles describing 168 cases of ExDS or AgDS, of which 104 (62%) were fatal. ExDS was diagnosed in 120 (71%) cases, and AgDS in 48 (29%). Fatalities were more likely to be diagnosed as ExDS (OR: 9.9, p < 0.0001). Aggressive restraint (i.e. manhandling, handcuffs, and hobble ties) was more common in ExDS (ORs: 4.7, 14, 29.2, respectively, p < 0.0001) and fatal cases (ORs: 7.4, 10.7, 50, respectively, p < 0.0001). Sedation was more common in AgDS and survived cases (OR:11, 25, respectively, p < 0.0001). The results of the study indicate that a diagnosis of ExDS is far more likely to be associated with both aggressive restraint and death, in comparison with AgDS. There is no evidence to support ExDS as a cause of death in the absence of restraint. These findings are at odds with previously published theories indicating that ExDS-related death is due to an occult pathophysiologic process. When death has occurred in an aggressively restrained individual who fits the profile of either ExDS or AgDS, restraint-related asphyxia must be considered a likely cause of the death.

A review of causal inference in forensic medicine.

The primary aim of forensic medical analysis is to provide legal factfinders with evidence regarding the causal relationship between an alleged action and a harmful outcome. Despite existing guides and manuals, the approach to formulating opinions on medicolegal causal inference used by forensic medical practitioners, and how the strength of the opinion is quantified, is mostly lacking in an evidence-based or systematically reproducible framework. In the present review, we discuss the literature describing existing methods of causal inference in forensic medicine, especially in relation to the formulation of expert opinions in legal proceedings, and their strengths and limitations. Causal inference in forensic medicine is unique and different from the process of establishing a diagnosis in clinical medicine. Because of a lack of tangibility inherent in causal analysis, even the term "cause" can have inconsistent meaning when used by different practitioners examining the same evidence. Currently, there exists no universally applied systematic methodology for formulating and assessing causality in forensic medical expert opinions. Existing approaches to causation in forensic medicine generally fall into two categories: intuitive and probabilistic. The propriety of each approach depends on the individual facts of an investigated injury, disease, or death. We opine that in most forensic medical settings, probabilistic causation is the most suitable for use and readily applicable. Forensic medical practitioners need, however, be aware of the appropriate approach to causation for different types of cases with varying degrees of complexity.

Central Sensitization Is Modulated Following Trigger Point Anesthetization in Patients with Chronic Pain from Whiplash Trauma. A Double-Blind, Placebo-Controlled, Crossover Study.

Objective: Central sensitization (CS) with low peripheral pain thresholds (PPTs) is a common finding among patients with chronic pain after whiplash (CPWI). While it has been proposed that myofascial myofascial trigger points (MTrPs) may act as modulators of central sensitization, previously reported findings are conflicting and inconclusive. The present study was designed to investigate immediate responsiveness of CS to alterations in nociceptive input. Design: Controlled, double-blind, cross-over. Subjects: Thirty-one patients with chronic pain (trapezius myalgia) and CS after whiplash. Methods: Participants were referred by randomization to group A for injection of a single peripheral pain generator (MTrP or other discrete tender point) with local anesthetic or to group B for sham injection and cross-over. Documentation of PPT (Algometer), maximum jaw opening (caliper), and grip strength (Vigorimeter), as well as subjective overall pain (visual analog scale [VAS]), was made before and after each intervention. Results: Statistical analysis of data (Student's t test, analysis of variance) confirmed that peripheral pain thresholds were significantly higher and maximum jaw opening significantly greater after anesthetizing a focal pain generator in the trapezius, but not after a sham injection. In contrast with the objective variables, subjective generalized pain improved (VAS) after not only an injection of local anesthetic, but also, and to a similar extent, after a sham injection. Conclusions: CS, as expressed by lowered PPT, is a rapidly adjusting physiological response to nociceptive stimuli in some patients with chronic pain after whiplash. PPT are likely modulated by myofascial tender points in selected patients with CS. With reference to the present findings, surgical ablation of MTrPs is discussed as a potential treatment modality for CS.

Correction to: A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions.

The published online version contains mistake in Acknowledgment Section. The author name "Steve Gorin, M.D." should have been "Steven Gorin, D.O, M.S.Ed.".

A review of the diversity in taxonomy, definitions, scope, and roles in forensic medicine: implications for evidence-based practice.

The scope, roles, and tasks of forensic medicine and forensic medical experts currently vary widely between countries and legal systems, which has resulted in barriers to organization, standard setting, and quality assurance for practice in forensic medicine, including for reporting. The legal fact finder is thus confronted with variability in the quality, structure, and content of forensic medical reports. We sought to define and categorize the scope, methods, and practices that fall under the description of forensic medicine, the various issues encountered in current forensic medical practice, and the potential role of evidence-based practice in forensic medicine. We searched electronic databases and reviewed relevant articles, as well as conducting personal correspondences with forensic medical practitioners around the world, to obtain a description of current forensic medical practice. The terms forensic medicine, legal medicine, medical jurisprudence, medico-legal services, forensic pathology, and clinical forensic medicine are used with mixed interpretations in different countries. The systems and services rendered are not uniform either. The methods used by forensic medical practitioners are not always evidence-based, or based on standardized methods, and vary greatly between experts and centers. There are also no universally accepted guidelines to prepare a standard and admissible report. The lack of a uniform system in forensic medicine creates difficulties in assessing the development and performance of forensic medicine as a distinct discipline. To prepare evidence-based forensic medical reports, generally accepted guidelines are necessary.

A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions.

INTRODUCTION: The purpose of the present investigation is to report on detailed complications among a much larger group of 2372 orthopaedic patients treated with stem cell injections who were followed in a treatment registry for up to nine years. METHODS: All patients underwent an MSC-based, percutaneous injection treatment of an orthopaedic condition between December 2005 and September 2014 at one of 18 clinical facilities. Treated areas of the body included the knee, hip, ankle/foot, hand/wrist, elbow, shoulder, and spine. The patients were followed prospectively via enrollment in a treatment registry. Patients were followed prospectively at one, three, six and 12 months, and annually thereafter, using an electronic system, ClinCapture software. RESULTS: A total of 3012 procedures were performed on 2372 patients with follow-up period of 2.2 years. A total of 325 adverse events were reported. The majority were pain post-procedure (n = 93, 3.9 % of the study population) and pain due to progressive degenerative joint disease (n = 90, 3.8 % of the study population). Seven cases reported neoplasms, a lower rate than in the general population. The lowest rate of adverse events was observed among patients injected with BMC alone. CONCLUSION: Lowest rate of adverse events was among those patients receiving BMC injections alone, but the higher rate of AEs for BMC plus adipose and cultured cells was readily explained by the nature of the therapy or the longer follow-up. There was no clinical evidence to suggest that treatment with MSCs of any type in this study increased the risk of neoplasm.

Risk factors for homicide victimization in post-genocide Rwanda: a population -based case- control study.

BACKGROUND: Homicide is one of the leading causes of mortality in the World. Homicide risk factors vary significantly between countries and regions. In Rwanda, data on homicide victimization is unreliable because no standardized surveillance system exists. This study was undertaken to identify the risk factors for homicide victimization in Rwanda with particular attention on the latent effects of the 1994 genocide. METHODS: A population-based matched case-control study was conducted, with subjects enrolled prospectively from May 2011 to May 2013. Cases of homicide victimization were identified via police reports, and crime details were provided by law enforcement agencies. Three controls were matched to each case by sex, 5-year age group and village of residence. Socioeconomic and personal background data, including genocide exposure, were provided via interview of a family member or through village administrators. Conditional logistic regression, stratified by gender status, was used to identify risk factors for homicide victimization. RESULTS: During the study period, 156 homicide victims were enrolled, of which 57 % were male and 43 % were female. The most common mechanisms of death were wounds inflicted by sharp instruments (knives or machetes; 41 %) followed by blunt force injuries (36.5 %). Final models indicated that risk of homicide victimhood increased with victim alcohol drinking patterns. There was a dose response noted for alcohol use: for minimal drinking versus none, adjusted odds ratio (aOR) = 3.1, 95%CI: 1,3-7.9; for moderate drinking versus none, aOR = 10.1, 95%CI: 3.7-24.9; and for heavy drinking versus none, aOR = 11.5, 95%CI: 3.6-36.8. Additionally, having no surviving parent (aOR = 2.7, 95%CI: 1.1-6.1), previous physical and/or sexual abuse (aOR = 28.1, 95%CI: 5.1-28.3) and drinking illicit brew and/or drug use (aOR = 7.7, 95%CI: 2.4-18.6) were associated with a higher risk of being killed. The test of interaction revealed that the variables that were significantly associated with a higher risk of homicide victimhood, did not exhibit any difference according to sex of the victim. However, the effect of belonging to a religion differed between women and men, but was significantly protective for both (aOR = 0.002, 95%CI: 0.001-0.054 and aOR = 0.20, 95%CI: 0.052-0.509, respectively). CONCLUSION: Homicide victims in Rwanda are relatively young and the proportion of female victims is one of the highest globally. Contrary to the initial study considerations, genocide exposure (either as a survivor or perpetrator) was not a significant predictor of homicide victimization. Rather, risk factors were similar to those described in other countries, regardless of gender status. Sensitizing communities against alcohol heavy drinking, and illicit brew drinking and/or drug abuse and physical or sexual violence could reduce the homicide rate in Rwanda.

A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis.

BACKGROUND: Prior studies describing the treatment of symptomatic knee osteoarthritis with injections of bone marrow concentrate have provided encouraging results. The relationship between the cellular dose contained within the bone marrow concentrate and efficacy of the treatment, however, is unclear. In the present study we describe clinical outcomes for symptomatic knee osteoarthritis in relation to higher and lower cell concentrations contained within a bone marrow concentrate treatment protocol. METHODS: Data from an ongoing patient registry was culled to identify 373 patients that received bone marrow concentrate injections for the treatment of 424 osteoarthritic knee joints. The clinical scales for these patients were assessed at baseline and then tracked post-procedure at 1, 3, 6 and 12 months, and annually thereafter. Tracked outcomes included the numeric pain scale; a lower extremity functional questionnaire; an International Knee Documentation Committee scale; and a subjective improvement rating scale. Using pain and functional outcome measures, a receiver operating characteristic analysis was used to define an optimal clinical outcome threshold at which bone marrow nucleated cell count could be divided into either a lower or higher cell count group within a treatment protocol. RESULTS: The lower and higher cell count groups were defined using a threshold of 4 × 10(8) cells. There were 224 and 185 knee joints treated in the lower (≤4 × 10(8)) and higher (>4 × 10(8)) cell count groups respectively. Most joints were diagnosed with early stage knee osteoarthritis. Both the lower and higher cell count groups demonstrated significant positive results with the treatment for all of the pain and functional metrics. The higher cell count group reported lower post treatment numeric pain scale values, in comparison with the lower cell count group (1.6 vs. 3.2; P < 0.001). No significant differences were detected for the other metrics, however. CONCLUSIONS: Improved function and reduced pain was observed in patients treated with a bone marrow concentrate protocol regardless of cellular dose; however, patients receiving a higher concentration of cells reported a better pain outcome in comparison with the lower dose group. These preliminary findings suggest that cell dose may be an important factor governing clinical outcomes in autologous bone marrow concentrate treatment of knee osteoarthritis. Further studies using a larger patient population may help elucidate these findings.

Fatal subarachnoid hemorrhage associated with internal carotid artery dissection resulting from whiplash trauma.

Spinal injury following inertial loading of the head and neck (whiplash) is a common sequel of low speed traffic crashes. A variety of non-musculoskeletal injuries have been described in association with injury to the spine following whiplash trauma, including traumatic brain injury, vestibular derangement, and cranial nerve injury, among others. Vascular injuries in the head and neck have, however, only rarely been described. We present the case of a middle-aged male who sustained an ultimately fatal injury that resulted from injury to the internal carotid artery (ICA) and intracerebral vascular structures following a hard braking maneuver, with no direct head- or neck contact with the vehicular interior. Based on this unusual mechanism of injury we reviewed hospital data from the United States nationwide inpatient database (NIS) to assess the frequency of similar injuries reportedly resulting from traffic crashes. The post-mortem examination revealed a left internal carotid artery dissection associated with subarachnoid hemorrhage (SAH). Based on the close temporal association, the absent prior history, and the plausibility of the injury mechanism, the injury was attributed to the braking maneuver. An analysis of NIS data demonstrated that the prevalence of subarachnoid hemorrhage is significantly higher when there is a traumatic etiology, and higher yet when the trauma is a traffic crash (odds ratio 3.3 and 4.3, respectively). The presented case, together with the hospital inpatient data analysis, indicate that although SAH in combination with ICA dissection is relatively rare, it is substantially more probable following a traffic crash. In a clinical or forensic setting the inference that magnitude of a trauma was low should not serve as a basis for either excluding a cervical artery dissection from a differential diagnosis, or for excluding the trauma as a cause of a diagnosed dissection. This case report illustrates a rare fatal outcome of inertial load to the head and neck induced by a sudden braking event in a commonly experienced non-collision traffic incident. The likely mechanism of injury resulted from interaction between the occupant and the 3-point seat belt. These findings indicate that ICA dissections are substantially more likely to be associated with SAH following head and neck trauma, regardless of the magnitude of the traumatic event or whether an impact was involved.

Percutaneous injection of autologous, culture-expanded mesenchymal stem cells into carpometacarpal hand joints: a case series with an untreated comparison group.

In the present study, we describe six patients who received autologous mesenchymal stem cell (MSC) therapy for symptomatic carpometacarpal (CMC) joint and hand osteoarthritis (OA). Six patients who received injections of adult autologous culture expanded MSCs in their thumb CMC joints were followed for 1 year posttreatment, and matched with four procedure candidates who remained untreated. We observed positive outcomes in the treatment group for both symptoms and function related to the OA, compared with a reported worsening among the untreated controls. While these results should be interpreted with caution because of the small number of treated subjects and lack of placebo control and randomization, we find sufficient evidence for further investigation of MSC therapy as an alternative to more invasive surgery in patients with OA of the hand.

Forensic epidemiology: a method for investigating and quantifying specific causation.

The field of forensic epidemiology was initially introduced as a systematic approach to the investigation of acts of bioterrorism. In recent years, however, the applications of forensic epidemiology have expanded greatly, covering a wide range of medicolegal issues routinely encountered in both criminal and civil court settings. Forensic epidemiology provides a method of evaluating causation in groups and individuals based in the application of the Hill Criteria, with conclusions given in terms of relative or comparative risk, or as a Probability of Causation. The purpose of this paper is to give a brief overview of the methods and applications of forensic epidemiology.

A predictive model for perinatal hypoxic ischemic encephalopathy using linked maternal and neonatal hospital data.

PURPOSE: To build an evidence-based model to estimate case-specific risk of perinatal hypoxic ischemic encephalopathy. METHODS: A retrospective, cross-sectional study of all births in Hawaii, Michigan, and New Jersey between 2010 and 2015, using linked maternal labor/delivery and neonatal birth records. Stepwise logistic regression and competitive Akaike information criterion were used to identify the most parsimonious model. Predictive ability of the model was measured with bootstrapped optimism-adjusted area under the ROC curve. RESULTS: Among 836,216 births there were 376 (0.45 per 1000) cases of hypoxic ischemic encephalopathy. The final model included 28 variables, 24 associated with increased risk, and 4 that were protective. The optimism-adjusted area under the ROC curve was 0.84. Estimated risk in the study population ranged from 1 in ∼323,000 to 1 in 2.5. The final model confirmed known risk factors (e.g., sentinel events and shoulder dystocia) and identified novel risk factors, such as maternal race and insurance status. CONCLUSION: Our study shows that risk of perinatal hypoxic ischemic encephalopathy injury can be estimated with high confidence. Our model fills a notable gap in the study of hypoxic ischemic encephalopathy prevention: the estimation of risk, particularly in the United States population which is unique with respect to racial and socioeconomic disparities.

Non-Surgical Management of Upper Cervical Instability via Improved Cervical Lordosis: A Case Series of Adult Patients.

Injury to the head and neck resulting from whiplash trauma can result in upper cervical instability (UCIS), in which excessive movement at C1 on C2 is observed radiologically. In some cases of UCIS there is also a loss of normal cervical lordosis. We postulate that improvement or restoration of the normal mid to lower cervical lordosis in patients with UCIS can improve the biomechanical function of the upper cervical spine, and thus potentially improve symptoms and radiographic findings associated with UCIS. Nine patients with both radiographically confirmed UCIS and loss of cervical lordosis underwent a chiropractic treatment regimen directed primarily at the restoration of the normal cervical lordotic curve. In all nine cases, significant improvements in radiographic indicators of both cervical lordosis and UCIS were observed, along with symptomatic and functional improvement. Statistical analysis of the radiographic data revealed a significant correlation (R2 = 0.46, p = 0.04) between improved cervical lordosis and reduction in measurable instability, determined by C1 lateral mass overhang on C2 with lateral flexion. These observations suggest that enhancing cervical lordosis can contribute to improvement in signs and symptoms of upper cervical instability secondary to traumatic injury.

Post-Traumatic Atlanto-Axial Instability: A Combined Clinical and Radiological Approach for the Diagnosis of Pathological Rotational Movement in the Upper Cervical Spine.

Post-traumatic rotational instability at the atlanto-axial (C1-2) joint is difficult to assess, much less quantify, due to the orientation and motion plane of the joint. Prior investigations have demonstrated that a dynamic axial CT scan, during which the patient maximally rotates the head right and left, can be used to evaluate and quantify the amount of residual overlap between the inferior articulating facet of C1 and the superior facet of C2, as an index of ligamentous laxity at the joint. We have previously demonstrated that a novel orthopedic test of rotational instability, the atlas-axis rotational test (A-ART), may have utility in identifying patients with imaging evidence of upper cervical ligament injury. In the present investigation, we assessed the correlation between a positive A-ART and a CT scan assessment of the relative quantity of residual C1-2 overlap, as a percent of the superior articulating facet surface area of C2. A retrospective review was conducted of the records of consecutive patients presenting to a physical therapy and rehabilitation clinic, over a 5-year period (2015-20) for chronic head and neck pain after whiplash trauma. The primary inclusion criteria were that the patient had undergone both a clinical evaluation with A-ART and a dynamic axial CT to evaluate for C1-2 residual facet overlap at maximum rotation. The records for a total of 57 patients (44 female/13 male) were identified who fit the selection criteria, and among these, there were 43 with a positive A-ART (i.e., "cases") and 14 with a negative A-ART (i.e., "controls). The analysis demonstrated that a positive A-ART was highly predictive of decreased residual C1-2 facet overlap: the average overlap area among the cases was approximately one-third that of the control group (on the left, 10.7% versus 29.1%, and 13.6% versus 31.0% on the right). These results suggest that a positive A-ART is a reliable indicator of underlying rotational instability at C1-2 in patients with chronic head and neck symptoms following whiplash trauma.

Injuries Due to Law Enforcement Use of Force in the United States, 2006-2015: Trends in Severity and by Race.

PURPOSE: The purpose of the study was to assess incidence and severity of hospital reported injuries related to law enforcement Use of Force (UoF) in the US over time, and by race. METHODS: Data from the National Emergency Department Sample from the Healthcare Cost and Utilization Project and the National Electronic Injury Surveillance System (NEISS-AIP) from US Consumer Product Safety Commission were queried to identify UoF injuries. Regression analysis, t-tests, and chi-square tests were used in the analysis. RESULTS: Between 2006-15, there were 529,259 emergency department admissions for UoF injury in the NEDS, and 870,779 admissions in the NEISS-AIP. In a model adjusting for year, sex, and age, the Injury Severity Score increased by 1.1% annually (p<0.0001). Black people were 6 times as likely to be admitted to the ED as White people or Native Americans/Alaska Natives, and 25 times as likely as Asians/Pacific Islanders. Black patients were 4 times as likely as White patients to be admitted as inpatients. Per arrest rate by race using FBI uniform crime reporting data, Black arrestees were 2.5-3.1 times as likely as any other race to be hospitalized for UoF injury. CONCLUSION: The results of the study demonstrate that US law enforcement are injuring civilians more frequently and severely over time, and that Black people are disproportionately affected.

Assessing specific causation of mesothelioma following exposure to chrysotile asbestos-containing brake dust.

BACKGROUND: The question of whether chrysotile asbestos-containing brake dust can plausibly serve as a cause of mesothelioma in an exposed individual has become a matter of heated debate in the medical literature despite multiple international, federal, and state governmental agencies acknowledging a causal association. OBJECTIVES: We describe and provide an analysis of various industry and academic perspectives contributing to the debate. METHODS: A framework is presented for evaluating the general and specific causal relationship between brake dust exposure and mesothelioma utilizing the principles of forensic epidemiology, and by applying the Bradford-Hill criteria. RESULTS AND CONCLUSIONS: We conclude that there is a "net" of evidence favoring a causal relationship between brake dust-associated chrysotile exposure and mesothelioma. The industry-sponsored position that there is insufficient evidence to support a contiguous "chain" of causation is specious from both a methodologic and evidentiary perspective. Finally, we suggest a semiquantitative approach for the evaluation of individual causation in putative cases of mesothelioma with a history of significant brake dust exposure.

An evaluation of applied biomechanics as an adjunct to systematic specific causation in forensic medicine.

Biomechanical tests of post hoc probability have been proposed by prior authors as reliable tests of causation in forensic settings. Biomechanical assessment of injury kinetics and kinematics is a potentially important tool in forensic medicine, but there is also the potential for misapplication. The most reliable application is when biomechanical analysis is used to explain injury mechanisms, such as how an injury may have occurred. When a biomechanical analysis is used as a means of determining whether, rather than how an injury has resulted from a traumatic exposure, then a lack of reliability of the methodology limits its application in forensic medicine. Herein, we describe a systematic assessment of causation by adapting established general causation principles to specific causation scenarios, and how biomechanical analysis of injury mechanics is properly used to augment such an approach in conjunction with the principles of forensic epidemiology. An example calculation of relative risk associated with cervical spine injury is provided as a representative probabilistic metric for assessing causation. The statistical benefits and limitations of biomechanical analysis are discussed as an adjunct to forensic medicine.