Opioid overdose death following criminal justice involvement: Linking statewide corrections and hospital databases to detect individuals at highest risk.

BACKGROUND: Persons who interact with criminal justice and hospital systems are particularly vulnerable to negative health outcomes, including overdose. However, the relationship between justice involvement, healthcare utilization and overdose risk is not well-understood. This data linkage study seeks to improve our understanding of the link between different types of justice involvement as well as hospital interaction and risk of fatal opioid overdose among persons with incarcerations, arrests and parole/probation records for drug and property crimes in Maryland. METHODS: Maryland statewide criminal justice records were obtained for 2013-2016. Data were linked at the person-level to an all-payer hospitalization database and overdose death records for the same years. Logistic regression was performed to determine which criminal justice and hospital characteristics were associated with greatest risk of overdose death. RESULTS: 89,591 adults had criminal-justice records and were included in the study. During the 2013-2016 study period, 4108 (4.59 %) were hospitalized for a non-fatal opioid overdose, and 519 (0.58 %) died of opioid overdose. Strongest risk factors for death included being older, being white, having had an inpatient or emergency hospitalization, having had more arrests, having been arrested for a drug charge (vs. property charge), having a misdemeanor drug charge (vs. a felony charge), and having been released from incarceration during the study period. CONCLUSION: Linking corrections and healthcare information can help advance understanding of risk and target overdose prevention interventions directed at justice-involved individuals with greatest need.

Predictors of Overdose Death Among High-Risk Emergency Department Patients With Substance-Related Encounters: A Data Linkage Cohort Study.

STUDY OBJECTIVE: Persons with substance use disorders frequently utilize emergency department (ED) services, creating an opportunity for intervention and referral to addiction treatment and harm-reduction services. However, EDs may not have the appropriate tools to distinguish which patients are at greatest risk for negative outcomes. We link hospital ED and medical examiner mortality databases in one state to identify individual-level risk factors associated with overdose death among ED patients with substance-related encounters. METHODS: This retrospective cohort study linked Maryland statewide ED hospital claims records for adults with nonfatal overdose or substance use disorder encounters in 2014 to 2015 with medical examiner mortality records in 2015 to 2016. Logistic regression was used to identify factors in hospital records associated with risk of opioid overdose death. Predicted probabilities for overdose death were calculated for hypothetical patients with different combinations of overdose and substance use diagnostic histories. RESULTS: A total of 139,252 patients had substance-related ED encounters in 2014 to 2015. Of these patients, 963 later experienced an opioid overdose death, indicating a case fatality rate of 69.2 per 10,000 patients, 6 times higher than that of patients who used the ED for any cause. Factors most strongly associated with death included having both an opioid and another substance use disorder (adjusted odds ratio 2.88; 95% confidence interval 2.04 to 4.07), having greater than or equal to 3 previous nonfatal overdoses (adjusted odds ratio 2.89; 95% confidence interval 1.54 to 5.43), and having a previous nonfatal overdose involving heroin (adjusted odds ratio 2.24; 95% confidence interval 1.64 to 3.05). CONCLUSION: These results highlight important differences in overdose risk among patients receiving care in EDs for substance-related conditions. The findings demonstrate the potential utility of incorporating routine data from patient records to assess risk of future negative outcomes and identify primary targets for initiation and linkage to lifesaving care.

External Compressive Bracing With Initial Reduction of Pectus Carinatum: Compliance Is the Key.

BACKGROUND: To assess the impact of manipulation and a tailored program for compressive bracing on the quality of life of patients with flexible pectus carinatum. METHODS: Two hundred forty-nine sequential patients attending a clinic for assessment of pectus carinatum deformities underwent outpatient manipulation and then followed a prescribed schedule of continuous external compressive bracing but without significant progressive tightening. RESULTS: There was successful sustained reduction of the deformity in 244 patients with high reported rates of concordance (98%) and satisfaction (94%). Patients experienced a reduction in symptoms of anxiety and depression (P < .001) and had improved body satisfaction (P < .001). Mild skin irritation occurred in 18% of patients (n = 44), and there were 2 severe cases of skin irritation, 1 of which resulted in abandonment of bracing. CONCLUSIONS: Manipulation and nontightening compressive bracing was associated with complete concordance, high levels of successful bracing, improved confidence, and reduced psychological morbidity.

Initial reduction of flexible pectus carinatum with outpatient manipulation as an adjunct to external compressive bracing: technique and early outcomes at 12 weeks.

INTRODUCTION: Our aim was to assess whether initial reduction with outpatient soft-tissue manipulation of flexible pectus carinatum deformity prior to external compressive bracing was associated with improved compliance and patient satisfaction compared to reported outcomes of external brace with progressive tightening. MATERIALS AND METHODS: From our observational cohort of 227 patients, 177 were felt appropriate to undergo initial reduction and soft tissue manipulation prior to immediate custom fitting of an external compressive brace. These patients then followed a prescriptive schedule of 12 weeks of continuous external bracing with subsequent follow-up in clinic. RESULTS: The reduction in Haller Index was maintained throughout the period of external bracing without the need for progressive tightening of the external brace. The treatment was associated with high levels of patient satisfaction and high patient concordance compared to other protocols. There were no major complications and minor complications included only skin irritation. CONCLUSIONS: Out-patient initial reduction with manipulation prior to external compressive bracing is a novel technique which resulted in excellent concordance and high rates of patient satisfaction and should be considered as an adjunct to standard external bracing techniques. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level II.

Predicting Opioid Overdose Deaths Using Prescription Drug Monitoring Program Data.

INTRODUCTION: Prescription Drug Monitoring Program data can provide insights into a patient's likelihood of an opioid overdose, yet clinicians and public health officials lack indicators to identify individuals at highest risk accurately. A predictive model was developed and validated using Prescription Drug Monitoring Program prescription histories to identify those at risk for fatal overdose because of any opioid or illicit opioids. METHODS: From December 2018 to July 2019, a retrospective cohort analysis was performed on Maryland residents aged 18-80 years with a filled opioid prescription (n=565,175) from January to June 2016. Fatal opioid overdoses were identified from the Office of the Chief Medical Examiner and were linked at the person-level with Prescription Drug Monitoring Program data. Split-half technique was used to develop and validate a multivariate logistic regression with a 6-month lookback period and assessed model calibration and discrimination. RESULTS: Predictors of any opioid-related fatal overdose included male sex, age 65-80 years, Medicaid, Medicare, 1 or more long-acting opioid fills, 1 or more buprenorphine fills, 2 to 3 and 4 or more short-acting schedule II opioid fills, opioid days' supply ≥91 days, average morphine milligram equivalent daily dose, 2 or more benzodiazepine fills, and 1 or more muscle relaxant fills. Model discrimination for the validation cohort was good (area under the curve: any, 0.81; illicit, 0.77). CONCLUSIONS: A model for predicting fatal opioid overdoses was developed using Prescription Drug Monitoring Program data. Given the recent national epidemic of deaths involving heroin and fentanyl, it is noteworthy that the model performed equally well in identifying those at risk for overdose deaths from both illicit and prescription opioids.

A predictive risk model for nonfatal opioid overdose in a statewide population of buprenorphine patients.

BACKGROUND: Predicting which individuals who are prescribed buprenorphine for opioid use disorder are most likely to experience an overdose can help target interventions to prevent relapse and subsequent consequences. METHODS: We used Maryland prescription drug monitoring data from 2015 to identify risk factors for nonfatal opioid overdoses that were identified in hospital discharge records in 2016. We developed a predictive risk model for prospective nonfatal opioid overdoses among buprenorphine patients (N = 25,487). We estimated a series of models that included demographics plus opioid, buprenorphine and benzodiazepine prescription variables. We applied logistic regression to generate performance measures. RESULTS: About 3.24% of the study cohort had ≥1 nonfatal opioid overdoses. In the model with all predictors, odds of nonfatal overdoses among buprenorphine patients were higher among males (OR = 1.39, 95% CI:1.21-1.62) and those with more buprenorphine pharmacies (OR = 1.19, 95% CI:1.11-1.28), 1+ buprenorphine prescription paid by Medicaid (OR = 1.21, 95% CI:1.02-1.48), Medicare (OR = 1.93, 95% CI:1.63-2.43), or a commercial plan (OR = 1.98, 95% CI:1.30-2.89), 1+ opioid prescription paid by Medicare (OR = 1.30, 95% CI:1.03-1.68), and more benzodiazepine prescriptions (OR = 1.04, 95% CI:1.02-1.05). The odds were lower among those with longer days of buprenorphine (OR = 0.64, 95% CI:0.60-0.69) or opioid (OR = 0.79, 95% CI:0.65-0.95) supply. The model had moderate predictive ability (c-statistic = 0.69). CONCLUSIONS: Several modifiable risk factors, such as length of buprenorphine treatment, may be targets for interventions to improve clinical care and reduce harms. This model could be practically implemented with common prescription-related information and allow payers and clinical systems to better target overdose risk reduction interventions, such as naloxone distribution.

Defining and Assessing Geriatric Risk Factors and Associated Health Care Utilization Among Older Adults Using Claims and Electronic Health Records.

BACKGROUND: Using electronic health records (EHRs), in addition to claims, to systematically identify patients with factors associated with adverse outcomes (geriatric risk) among older adults can prove beneficial for population health management and clinical service delivery. OBJECTIVE: To define and compare geriatric risk factors derivable from claims, structured EHRs, and unstructured EHRs, and estimate the relationship between geriatric risk factors and health care utilization. RESEARCH DESIGN: We performed a retrospective cohort study of patients enrolled in a Medicare Advantage plan from 2011 to 2013 using both administrative claims and EHRs. We defined 10 individual geriatric risk factors and a summary geriatric risk index based on diagnosed conditions and pattern matching techniques applied to EHR free text. The prevalence of geriatric risk factors was estimated using claims, structured EHRs, and structured and unstructured EHRs combined. The association of geriatric risk index with any occurrence of hospitalizations, emergency department visits, and nursing home visits were estimated using logistic regression adjusted for demographic and comorbidity covariates. RESULTS: The prevalence of geriatric risk factors increased after adding unstructured EHR data to structured EHRs, compared with those derived from structured EHRs alone and claims alone. On the basis of claims, structured EHRs, and structured and unstructured EHRs combined, 12.9%, 15.0%, and 24.6% of the patients had 1 geriatric risk factor, respectively; 3.9%, 4.2%, and 15.8% had ≥2 geriatric risk factors, respectively. Statistically significant association between geriatric risk index and health care utilization was found independent of demographic and comorbidity covariates. For example, based on claims, estimated odds ratios for having 1 and ≥2 geriatric risk factors in year 1 were 1.49 (P<0.001) and 2.62 (P<0.001) in predicting any occurrence of hospitalizations in year 1, and 1.32 (P<0.001) and 1.34 (P=0.003) in predicting any occurrence of hospitalizations in year 2. CONCLUSIONS: The results demonstrate the feasibility and potential of using EHRs and claims for collecting new types of geriatric risk information that could augment the more commonly collected disease information to identify and move upstream the management of high-risk cases among older patients.

Melt-Quenched Glasses of Metal-Organic Frameworks.

Crystalline solids dominate the field of metal-organic frameworks (MOFs), with access to the liquid and glass states of matter usually prohibited by relatively low temperatures of thermal decomposition. In this work, we give due consideration to framework chemistry and topology to expand the phenomenon of the melting of 3D MOFs, linking crystal chemistry to framework melting temperature and kinetic fragility of the glass-forming liquids. Here we show that melting temperatures can be lowered by altering the chemistry of the crystalline MOF state, which provides a route to facilitate the melting of other MOFs. The glasses formed upon vitrification are chemically and structurally distinct from the three other existing categories of melt-quenched glasses (inorganic nonmetallic, organic, and metallic), and retain the basic metal-ligand connectivity of crystalline MOFs, which connects their mechanical properties to their starting chemical composition. The transfer of functionality from crystal to glass points toward new routes to tunable, functional hybrid glasses.

A Computational and Experimental Approach Linking Disorder, High-Pressure Behavior, and Mechanical Properties in UiO Frameworks.

Whilst many metal-organic frameworks possess the chemical stability needed to be used as functional materials, they often lack the physical strength required for industrial applications. Herein, we have investigated the mechanical properties of two UiO-topology Zr-MOFs, the planar UiO-67 ([Zr6O4(OH)4 (bpdc)6], bpdc: 4,4'-biphenyl dicarboxylate) and UiO-abdc ([Zr6O4(OH)4 (abdc)6], abdc: 4,4'-azobenzene dicarboxylate) by single-crystal nanoindentation, high-pressure X-ray diffraction, density functional theory calculations, and first-principles molecular dynamics. On increasing pressure, both UiO-67 and UiO-abdc were found to be incompressible when filled with methanol molecules within a diamond anvil cell. Stabilization in both cases is attributed to dynamical linker disorder. The diazo-linker of UiO-abdc possesses local site disorder, which, in conjunction with its longer nature, also decreases the capacity of the framework to compress and stabilizes it against direct compression, compared to UiO-67, characterized by a large elastic modulus. The use of non-linear linkers in the synthesis of UiO-MOFs therefore creates MOFs that have more rigid mechanical properties over a larger pressure range.

Postsynthetic bromination of UiO-66 analogues: altering linker flexibility and mechanical compliance.

A new member of the UiO-66 series of zirconium metal-organic frameworks (MOFs) is reported, and the postsynthetic bromination of its integral alkene moeities in a single-crystal to single-crystal manner is fully characterised. Nanoindentation is used to probe the bromination of unsaturated carbon-carbon bonds, in it and an analogous Zr MOF, which leads to more compliant materials with lower elastic moduli.

Zalutumumab in head and neck cancer.

INTRODUCTION: Over 90% of head and neck cancers overexpress EGFR. This correlates with advanced disease stage and worse prognosis. Strategies to inhibit the EGFR pathway have been developed over the last decade. Zalutumumab is a recent high-affinity completely human IgG1k antibody targeting EGFR. AREAS COVERED: The mechanism of action and data on efficacy and safety of zalutumumab in head and neck cancer. EXPERT OPINION: Zalutumumab has demonstrated acceptable toxicity in head and neck cancer patients, with rash being the most common adverse event. The toxicity profile makes zalutumumab an attractive option for patients who are heavily pretreated and/or have poor performance status due to concurrent co-morbidities. As the molecule is fully human, the likelihood of hypersensitivity to the drug is low. Zalutumumab may be effective at low concentrations through antibody-dependent cellular cytotoxicity. Current data from Phase I and II trials identify zalutumumab as a promising drug for the treatment of locally advanced head and neck cancer and recent data from a Phase III randomized trial showed encouraging survival results compared with best supportive care. Results from other ongoing Phase III trials will provide clarification on zalutumumab as a treatment option. The clinical development of this compound has been suspended from June 2011 until a development and commercialization partner is found.

Multidisciplinary care of the dying adolescent.

The adolescent at the end of life poses a unique combination of challenges resulting from the collision of failing health with a developmental trajectory meant to lead to attainment of personal independence. Because virtually all spheres of the dying adolescent's life are affected, optimal palliative care for these young persons requires a multidisciplinary team whose members have a good understanding of their complementary roles and a shared commitment to providing well-coordinated care. Members of the team include the physician (to initiate and coordinate palliative care management); the nurse (to work collaboratively with the physician and adolescent, especially through effective patient advocacy); the psychologist (to assess and manage the patient's neurocognitive and emotional status); the social worker (to assess and optimize support networks); the chaplain (to support the adolescent's search for spiritual meaning); and the child life specialist (to facilitate effective communication in preparing for death). A crucial area for dying adolescents is medical decision making, where the full range of combined support is needed. By helping the young person continue to develop personal autonomy, the multidisciplinary team will enable even the dying adolescent to experience dignity and personal fulfillment.