Quantifying drug overdose deaths: A troubled path from start to finish.

Between 1999 and 2019, according to the Centers for Disease Control and Prevention (CDC), nearly 450,000 people died from overdoses involving prescribed opioids. This review examines how drug overdose deaths are compiled by the CDC using the coding system of the International Classification of Diseases (ICD). When it comes to drug-involved deaths, the ICD may not tell the whole story or even the right story. To learn why, the authors examined the CDC's source data and the standard death certificate. In fatal drug overdose cases, death certificates are issued often before the results of post-mortem toxicology are known by the certifier. The CDC believes that this delay in the death investigation process may account for errors when, for example, certifiers list ambiguous terms such as "suspected acute drug intoxication" or "possible drug overdose" as a cause of death. When incomplete data are coded according to the ICD, the error is passed along while potentially useful information is lost. The result may reflect accurately the annual total of drug-involved overdose deaths while obscuring the lethality of individual substances, consumed alone or in combination, which contributed to, or caused, drug-involved deaths. The true cause of most fatal drug overdoses-polysubstance abuse-often is lost in this process. A key objective of this paper is to describe the process used by the CDC to report drug-involved mortality and how the current iteration of the ICD may be ill-suited for this important task.

What Your Death Certificate Says About You May Be Wrong: A Narrative Review on CDC's Efforts to Quantify Prescription Opioid Overdose Deaths.

Mortality data in most countries are reported using the International Classification of Diseases (ICD), managed by the WHO. In this paper, we show how the ICD is ill-suited for classifying drug-involved deaths, many of which involve polysubstance abuse and/or illicitly manufactured fentanyl (IMF). Opioids identified in death certificates are categorized according to six ICD T-codes: opium (T40.0), heroin (T40.1), methadone (T40.3), other synthetic narcotics (T40.4), and other and unspecified narcotics (T40.6). Except for opium, heroin, and methadone, all other opioids except those that are unspecified are aggregated in two T-codes (T40.2 and T40.4), depending upon whether they are natural/semisynthetic or synthetic opioids other than methadone. The result is a system that obscures the actual cause of most drug overdose deaths and, instead, just tallies the number of times each drug is mentioned in an overdose situation. We examined the CDC's methodology for coding other controlled substances according to the ICD and found that, besides fentanyl, the ICD does not distinguish between other licit and illicitly manufactured controlled substances. Moreover, we discovered that the CDC codes all methadone-related deaths as resulting from the prescribed form of the drug. These and other anomalies in the CDC's mortality reporting are discussed in this report. We conclude that the CDC was at fault for failing to correct the miscoding of IMF. Finally, we briefly discuss some of the public policy consequences of this error, the misguided focus by public health and safety officials on pharmaceutical opioids, their prescribers and users, and the pressing necessity for the CDC to reassess how it measures and reports drug-involved mortality.

CDC's Efforts to Quantify Prescription Opioid Overdose Deaths Fall Short.

In a 2018 report titled, Quantifying the Epidemic of Prescription Opioid Overdose Deaths, four senior analysts of the Centers for Disease Control and Prevention (CDC), including the head of the Epidemiology and Surveillance Branch, acknowledged for the first time that the number of prescription opioid overdose deaths reported by the CDC in 2016 was erroneous. The error, they said, was caused by miscoding deaths involving illicitly manufactured fentanyl (IMF) as deaths involving prescribed fentanyl. To understand what caused this error, the authors examined the CDC's methodology for compiling drug-related mortality data, beginning with the source data obtained from approximately 2.8 million death certificates received each year from state vital statistics registrars. Systemic problems often begin outside the CDC, with a surprisingly high rate of errors and omissions in the source data. Using the CDC's explanation for what caused the error, the authors show why an international program used by the CDC for reporting mortality is ill-suited for compiling and reporting drug overdose deaths. Except for heroin, methadone, and opium, each of which has an individual program code, all other opioids are separated in just two program codes according to whether they are synthetic or semisynthetic/opiates. Methadone-involved deaths pose a special problem for the CDC because methadone has dual indications for treating pain and for treating opioid use disorder (OUD). In 2019, more than seven times more methadone was administered or dispensed for OUD treatment than was prescribed for pain, yet all methadone-involved deaths are coded by the CDC as involving the prescribed form of the drug. The authors conclude that the CDC was at fault for failing to recognize and correct this problem before 2016. Public policy consequences of this failure are briefly mentioned.

Academic plastic surgery: faculty recruitment and retention.

BACKGROUND: A critical element of a thriving academic plastic surgery program is the quality of faculty. A decline in recruitment and retention of faculty has been attributed to the many challenges of academic medicine. Given the substantial resources required to develop faculty, academic plastic surgery has a vested interest in improving the process of faculty recruitment and retention. METHODS: The American Council of Academic Plastic Surgeons Issues Committee and the American Society of Plastic Surgeons/Plastic Surgery Foundation Academic Affairs Council surveyed the 83 existing programs in academic plastic surgery in February of 2012. The survey addressed the faculty-related issues in academic plastic surgery programs over the past decade. Recruitment and retention strategies were evaluated. This study was designed to elucidate trends, and define best strategies, on a national level. RESULTS: Academic plastic surgery programs have added substantially more full-time faculty over the past decade. Recruitment efforts are multifaceted and can include guaranteed salary support, moving expenses, nurse practitioner/physician's assistant hires, protected time for research, seed funds to start research programs, and more. Retention efforts can include increased compensation, designation of a leadership appointment, protected academic time, and call dilution. CONCLUSIONS: Significant change and growth of academic plastic surgery has occurred in the past decade. Effective faculty recruitment and retention are critical to a successful academic center. Funding sources in addition to physician professional fees (institutional program support, grants, contracts, endowment, and so on) are crucial to sustain the academic missions.

Refractory bleeding from a chest wall sarcoma: a rare indication for palliative resection.

We report a case of a 57-year-old male who presented with an inoperable chest wall sarcoma due to numerous pulmonary metastases and was treated with chemotherapy and radiation therapy. The patient subsequently developed refractory bleeding from the chest wall tumor requiring palliative chest wall resection and reconstruction. The patient made an uneventful recovery however died from metastatic disease 8 months later. This case represents a very rare indication for palliative chest wall resection.

Preemptive use of high-frequency oscillatory ventilation in pediatric burn patients.

There is a high incidence of developing acute respiratory distress syndrome (ARDS) in pediatric patients with major burns, and this development leads to higher mortality. High-frequency oscillatory ventilation (HFOV) has been used to treat pediatric patients with severe ARDS. The decision of when to start HFOV in the pediatric burn victim with ARDS is debatable. We hypothesize that earlier institution of HFOV in these patients may lead to better outcomes. A single center, retrospective chart review of pediatric burn patients with ARDS from 1996 to 2007 was completed. Daily partial pressure of oxygen in arterial blood (P(a)O(2)):fraction of inspired oxygen (F(i)O(2)) and oxygenation index was calculated for each patient. Means and SDs were compared for those treated with early (0-48 hours) institution of HFOV with those who received it late (48-72 hours). We found a trend toward improved P(a)O(2):F(i)O(2) and oxygenation index (OI) in the early treated group; however, this trend was not statistically significant. There was no statistically significant difference in length of stay, length of time on HFOV, or adverse events. There was, however, a trend toward more barotraumas in the late treated group. Early (within 24-36 hours of burn injury) HFOV may improve P(a)O(2):F(i)O(2) and OI in patients with major burns. A multicenter prospective trial is needed to have enough statistical power to answer questions of P(a)O(2):F(i)O(2) and OI improvement at statistically significant level, as well as to determine whether there is any overall survival benefit.

The supply chain of medicinal controlled substances: addressing the Achilles heel of drug diversion.

The escalation of prescription drug abuse in the U.S. has attracted the attention of public health and safety officials as well as others puzzled by how such a tightly regulated enterprise could so easily be breached by those seeking controlled substances for nonmedical use. Prescribers and patients who use, misuse, or, in some cases, redistribute or divert these drugs have figured prominently in government strategies aimed at addressing this issue. This review departs from this paradigm and focuses on wholesale drug distributors, a highly efficient and largely behinds-the-scene link in the supply chain of controlled substances. By law, distributors are required to identify and report to the Drug Enforcement Administration (DEA) orders for controlled substances that are suspicious and may indicate drug diversion. Ten cases are examined in which distributors were each charged with failing to prevent the diversion of millions of doses of controlled substances. Special attention is given to a payment system employed by the industry that may encourage this unlawful commerce. Court records, agency and industry reports, and other published sources are used to document referenced cases and their disposition, and recommendations are offered for improving distributors' compliance with the law.

Cheese: an old drug in a new wrapper.

BACKGROUND: An unexpected outbreak of "cheese" heroin, which contained diphenhydramine and usually acetaminophen, began in Dallas around 2004. Onset occurred among youths living in neighborhoods populated by first-generation Hispanic immigrants. Little was known about the problem or the social strengths and deficits of these youth, who were primarily inhalers ("snorters") but at risk of transitioning to injection. METHODS: Multiple data sources were used, including surveys, data from emergency departments, law enforcement, treatment programs, and coroner, and interviews with users and key informants. RESULTS: Among heroin users under age 20, overdose deaths peaked in 2006, the school survey responses to using "cheese" heroin peaked in 2007, and treatment admissions peaked in 2008. Hispanic youth entering treatment were less likely to be injectors and report fewer problems than their Anglo counterparts and they were more likely to live with their families and to be supported by them. Sixty percent of the Hispanic youth had been in treatment previously and only 53% completed treatment. Cocaine and/or benzodiazepines were involved in 32% of the adolescent heroin deaths. CONCLUSIONS: The timely use of multiple data sources enabled this outbreak to be quickly identified and monitored, and the Cheese Heroin Task Force used the collected data to help respond to the problem, although retention in treatment and readmissions remained problematic. Cultural problems including immigration status, language, and misunderstandings about the nature of treatment were barriers to successful treatment outcomes. Completion of treatment as an inhaler is critical to reducing the likelihood of transitioning to injection.

High-frequency oscillatory ventilators in burn patients: experience of Riley Hospital for Children.

The objective of the study is to review a single institution's experience with high-frequency oscillatory ventilation (HFOV) and compare patient characteristics, outcomes, and complications with other reported studies of HFOV use in burn patients with acute respiratory distress syndrome and respiratory failure. This study is a retrospective chart review of the burn patients treated with HFOV in Pediatric Burn Unit at Riley Hospital for Children from October 1996 to April 2007. Patient data were collected, including demographics, percentage of TBSA burn, percentage of full-thickness burn, mechanisms of burn, settings on conventional mechanical ventilation and HFOV, and blood gas data before initiation of HFOV and at 1, 3, 6, 12, 24, 72 (3 days), 120 (5 days), 168 (7 days), 240 (10 days), and 336 hours (14 days). Length of stay, mortality, and complications were also included. HFOV was used 24 times in 21 patients between October 1996 and April 2007 with a mean age of 10 ± 11 years. At initiation of HFOV, the PaO2/FiO2 and oxygenation index values were 109 ± 26 and 36 ± 12, respectively. At stop, the PaO2/FiO2 improved to 166 ± 24 with an average increase from before HFOV of 57 ± 39 (P < .002). At 5 days of HFOV, oxygenation index improved to 14.1 ± 1.7 (P < .02) but did not significantly improve at discontinuation of HFOV at 28.8 ± 6.2 (P = .11). The mortality rate during admission to the burn unit was 29%. Barotrauma occurred in 38% of patients during HFOV. Severe hypercapnea was present briefly in 49% of patients, and this was refractory to standard treatment in 19%. In our experience, HFOV in severe burn patients has significant, early, and sustained improvement in oxygenation. Earlier institution of HFOV seems to significantly lower rates of barotraumas.

Issues and critiques of the forthcoming risk evaluation and mitigation strategy (REMS) for opioids in pain management.

OBJECTIVE: To examine the history and suitability of the Food and Drug Administration's (FDA) Risk Evaluation and Mitigation Strategy (REMS) for reducing the safety risks associated with the use of opioid medications, including the risks of abuse and overdose. This article will highlight recent attempts by the FDA to introduce a class wide REMS for new and existing Schedule II long-acting opioid drugs. A critique of these current REMS efforts and recommendations for the future will also be provided. DESIGN: A literature review and commentary design are utilized to highlight issues surrounding REMS efforts and to explore possible future directions. Expert opinion is offered to potentially guide future efforts in this arena. CONCLUSIONS: The stated goal of the FDA's proposed class wide opioid REMS program is to decrease abuse, misuse, addiction and overdose deaths from opioid medications. While the REMS program may have theoretical capabilities for evaluating and addressing problematic drug use among prescribed patients, it is unlikely to reduce the bulk of prescription drug abuse that occurs with non-patients. Our recommendations provide some ideas on how the REMS program can be improved to achieve the goals set for it by Congress and the FDA.

Legal liability perspectives on abuse-deterrent opioids in the treatment of chronic pain.

Abuse-deterrent opioid analgesic formulations can help reduce the risk of opioid diversion and abuse. Not all opioid analgesics are available as both extended- and immediate-release dosage forms in abuse-deterrent formulations. Clinicians may have to balance the clinical benefit of a product that does not use abuse-deterrent technology versus the regulatory benefit of using a product with this technology. There is the possibility that a health care professional may be held legally liable when a product without abuse-deterrent qualities is used and a person suffers harm that would not have occurred had an abuse-deterrent formulation been provided. This article reviews legal precedents that inform an understanding of the need to reduce malpractice exposure by identifying patients who are at high risk of opioid diversion and/or abuse and considering the use of an abuse-deterrent formulation for these patients.

Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy.

PURPOSE: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. METHODS AND MATERIALS: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm(2) wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. RESULTS: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. CONCLUSIONS: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

Cultured epithelial autografts for coverage of large burn wounds in eighty-eight patients: the Indiana University experience.

Since 1990, the authors have used a new technique for coverage of large burns, which begins with early tangential excision and coverage with cadaver allograft (A), followed by placement of cultured epithelial autograft (CEA) onto an allodermis base (CEA/A). They present their 18-year experience (1990-present) using CEA in 88 patients (20 children and 68 adults) with age range of 6 months to 73 years. A review of prospectively collected data was conducted on adult and pediatric patients grafted with CEA at the Indiana University Medical Center for definitive wound coverage (TBSA 28-98%). These patients were followed up for 3 to 90 months. Complications, take rates, and outpatient follow-ups were noted. The mean final take rate of CEA/A was 72.7%, and the overall patient survival rate was 91% (80 of 88 patients). Complications were classified as early and late, they included: (early) blistering and shearing (31%), pruritus and itching (4.7%), (late) CEA loss (2 patients, 2.3%), and wound contractures (66%). Contracture releases were performed on 32 patients (36%); of which, 18 were children (56%). Cultured keratinocytes provide an excellent alternative or adjunct to conventional split-thickness skin grafting in treating large burn wounds. A dedicated team of physicians, nurses, and therapists well rehearsed in CEA care are vital for success in keratinocyte grafting. The final graft take of 72.7% with a 91% overall survival rate gives much optimism for continuing to use CEA in critically burned patients.

Risk management and post-marketing surveillance for the abuse of medications acting on the central nervous system: expert panel report.

The abuse and diversion of medications is a significant public health problem. This paper is part of a supplemental issue of Drug and Alcohol Dependence focused on the development of risk management plans and post-marketing surveillance related to minimizing this problem. The issue is based on a conference that was held in October 2008. An Expert Panel was formed to provide a summary of the conclusions and recommendations that emerged from the meeting involving drug abuse experts, regulators and other government agencies, pharmaceutical companies and professional and other non-governmental organizations. This paper provides a written report of this Expert Panel. Eleven conclusions and 11 recommendations emerged concerning the state of the art of this field of research, the regulatory and public health implications and recommendations for future directions. It is concluded that special surveillance tools are needed to detect the emergence of medication abuse in a timely manner and that risk management tools can be implemented to increase the benefit to risk ratio. The scientific basis for both the surveillance and risk management tools is in its infancy, yet progress needs to be made. It is also important that the unintended consequences of increased regulation and the imposition of risk management plans be minimized.

Coverage of large pediatric wounds with cultured epithelial autografts in congenital nevi and burns: results and technique.

The use of cultured epithelial autografts (CEA) for the treatment of large burn wounds has gained popularity in recent years. This technique may circumvent the restrictions of limited donor site availability and hasten permanent wound coverage for large TBSA burns. The availability of a large amount of skin from a small donor site with the promise of permanent wound coverage suggests its use in other conditions such as giant congenital nevi (GCN) as well. The risk of malignant transformation of GCN to melanoma although somewhat controversial is significant enough to warrant early excision in childhood. Cultured keratinocytes may provide one-stage coverage of these large wounds, lessening the number of surgeries and the inherent staging problems of tissue expansion or autografting. A retrospective single institution review of was done for 29 children (20 burns and 9 patients with GCN) who underwent coverage of their large surface area wounds with CEA over an 18-year period. Excellent take rates were noted; 76.4% for burn patients and 66% for patients with GCN. Several strategies in preoperative, perioperative, and postoperative care have been standardized and have helped improve outcome. The keys to success with the CEA technique have been aggressive control of wound sepsis, surgical technique, specific use of topical antimicrobials, dressings, and the standardization of nursing and physiotherapy care. Although the cost of CEA is high, the benefits to patient care make this technique an appealing choice for large wound coverage in the pediatric population.

Killer fentanyl: is the fear justified?

BACKGROUND: Fentanyl-related deaths have created havoc with public health and safety, especially in the United States. With this increasingly apparent role as a drug of abuse in cases of overdose and death, the drug has acquired the reputation of 'killer fentanyl'. Is this fear justified? OBJECTIVE/METHODS: Information to clarify some of the present concerns regarding fentanyl abuse based on the review of the scientific literature in major databases and public sourced material available on the internet, followed by a quality assessment of reports. RESULTS/CONCLUSION: The opioid drug, fentanyl, is involved in medical cases of complications, toxic effects, addiction, abuse, overdose and death in patients, as well as abuse among healthcare professionals. The increase of fentanyl abuse is a growing public health problem that may evolve into a global problem. However, abuse patterns of legally and illegally produced fentanyl have produced confusion because media reporters and public officials often ignore important differences in the origins of the drug itself and the people who abuse it. In the light of possible fatal and nonfatal side effects, the use of fentanyl should be reconsidered, especially in view of the new opioid drugs that are now available.

Characteristics and motives of college students who engage in nonmedical use of methylphenidate.

Methylphenidate (MPH) has a long history of being an effective medication for attention deficit/hyperactivity disorder (ADHD). Recently, the nonmedical use of MPH has increased, particularly among college students. To investigate this, we surveyed 2,087 students regarding MPH misuse. Of 2,087 respondents, 110 (5.3%) used MPH nonmedically at least once. Most obtained MPH free from a friend, acquaintance, or family member. Misuse of Ritalin(R) occurred four times more frequently than Concerta. Among Ritalin abusers, Intranasal use was reported more often than oral. Students reported using MPH nonmedically for recreational reasons as well as to improve academic performance.

School-based administration of ADHD drugs decline, along with diversion, theft, and misuse.

Since 2000 researchers have reported a decline in the administration of attention-deficit/hyperactivity disorder (ADHD) medications given by school nurses, although no decline has been noted in the incidence of ADHD in school-age populations. Government data for the same period show reduced levels of methylphenidate abuse as measured by its involvement in hospital emergency department (ED) admissions. Offsetting this, however, is an increase in the involvement of amphetamine-dextroamphetamine in hospital ED admissions for the same period. Because ADHD medications are often administered in the school setting, a survey of school nurses was undertaken to identify factors related to the administration as well as to the diversion, theft, and misuse of ADHD medications. Of 311 school nurses responding, 295 (95%) reported a significant or moderate decline between 2002 and 2004 in the need for school-based administration of ADHD medications. Respondents also reported reductions in diversion, theft, and misuse of ADHD drugs.