The evolution of fentanyl-related substances: Prevalence and drug concentrations in postmortem biological specimens at the Miami-Dade Medical Examiner Department.

Since 2014, the Miami-Dade Medical Examiner Department (MDME) has observed a drastic increase in the number of fentanyl and fentanyl analog (fentanyl-related substances (FRSs)) fatalities since its introduction into the heroin and cocaine supply. Due to the prevalence of FRS in Miami-Dade County, the MDME toxicology laboratory began documenting each case in which fentanyl and/or a fentanyl analog was identified. Additional information monitored included demographics (age, race and sex), other drugs identified, cause of death (COD) and manner of death (MOD). From 2014 to 2022, the MDME toxicology laboratory analyzed a total of 1,989 cases that tested positive for FRS, of which 1,707 had detectable and/or quantifiable fentanyl concentrations in postmortem cases. The majority of decedents were white males (62%), and the predominant age range was 25-34 years. The most prevalent MOD was accident (93%) with the most common COD listed as acute combined drug toxicity of fentanyl in combination with other drugs (79%). Other drugs found in combination with fentanyl included heroin, cocaine (most prevalent), synthetic cathinones and ethanol. Of all FRS cases, 9% (170 cases) involved fentanyl alone as a COD, while 2% (38 cases) included only fentanyl analogs. Fentanyl concentrations ranged from 1.0 to 1,646 ng/mL in peripheral blood, 1.2 to 449 ng/mL in central blood, 3.2 to 28 ng/mL in donor blood (obtained during tissue harvesting), 1.1 to 108 ng/mL in antemortem blood, 8.5 to 1,130 ng/g in liver and 2.0 to 471 ng/g in brain. Drug concentrations were also reported for an additional eight fentanyl analogs. Considering the prevalence, high potency and constant evolution of FRS, it is important to continuously monitor trends and report drug concentrations in complex medical examiner casework in an effort to educate pathologists, law enforcement and local governments.

Prevalence of xylazine in overdose cases: An analysis of Miami-Dade County medical examiner case data.

Xylazine sedative, muscle relaxant, and analgesic used in a veterinary setting. Although xylazine was never approved for therapeutic use in humans, it has become popular in the street drug market as a cutting or bulking agent in the fentanyl and heroin supply. Recently, there has been a significant increase in the detection of xylazine in postmortem forensic toxicology casework. Xylazine can be identified during routine toxicology screening utilizing instrumentation such as gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Using the Miami-Dade Medical Examiner's LIMS system, all cases received between 2015 and 2022 in which xylazine was reported were reviewed. The cases studied include accidental drug overdose deaths in Miami-Dade County as well as Collier County (Naples), Florida. In total, there are 170 cases; the majority are accidental polydrug overdoses involving White males between the ages of 25 and 44 years old. Of the 170 cases, 37% listed xylazine as the cause of death. 13% of cases contained only xylazine and fentanyl while the remaining 87% of deaths were attributed to polydrug toxicity involving two or more substances. The prevalence of xylazine can be attributed to its increasing popularity rather than an increase in caseload. In 2019, xylazine was present in only 4% of all accidental fentanyl overdoses. By 2021, this percentage has increased sixfold, with xylazine present in 24% of all accidental fentanyl overdoses. Despite a decrease in fentanyl overdoses in 2022, the percentage of xylazine detection remained the same.

Evaluation and development of a novel binocular treatment (I-BiT™) system using video clips and interactive games to improve vision in children with amblyopia ('lazy eye'): study protocol for a randomised controlled trial.

BACKGROUND: Amblyopia (lazy eye) affects the vision of approximately 2% of all children. Traditional treatment consists of wearing a patch over their 'good' eye for a number of hours daily, over several months. This treatment is unpopular and compliance is often low. Therefore results can be poor. A novel binocular treatment which uses 3D technology to present specially developed computer games and video footage (I-BiT™) has been studied in a small group of patients and has shown positive results over a short period of time. The system is therefore now being examined in a randomised clinical trial. METHODS/DESIGN: Seventy-five patients aged between 4 and 8 years with a diagnosis of amblyopia will be randomised to one of three treatments with a ratio of 1:1:1 - I-BiT™ game, non-I-BiT™ game, and I-BiT™ DVD. They will be treated for 30 minutes once weekly for 6 weeks. Their visual acuity will be assessed independently at baseline, mid-treatment (week 3), at the end of treatment (week 6) and 4 weeks after completing treatment (week 10). The primary endpoint will be the change in visual acuity from baseline to the end of treatment. Secondary endpoints will be additional visual acuity measures, patient acceptability, compliance and the incidence of adverse events. DISCUSSION: This is the first randomised controlled trial using the I-BiT™ system. The results will determine if the I-BiT™ system is effective in the treatment of amblyopia and will also determine the optimal treatment for future development. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01702727.

Low strength of deep San Andreas fault gouge from SAFOD core.

The San Andreas fault accommodates 28-34 mm yr(-1) of right lateral motion of the Pacific crustal plate northwestward past the North American plate. In California, the fault is composed of two distinct locked segments that have produced great earthquakes in historical times, separated by a 150-km-long creeping zone. The San Andreas Fault Observatory at Depth (SAFOD) is a scientific borehole located northwest of Parkfield, California, near the southern end of the creeping zone. Core was recovered from across the actively deforming San Andreas fault at a vertical depth of 2.7 km (ref. 1). Here we report laboratory strength measurements of these fault core materials at in situ conditions, demonstrating that at this locality and this depth the San Andreas fault is profoundly weak (coefficient of friction, 0.15) owing to the presence of the smectite clay mineral saponite, which is one of the weakest phyllosilicates known. This Mg-rich clay is the low-temperature product of metasomatic reactions between the quartzofeldspathic wall rocks and serpentinite blocks in the fault. These findings provide strong evidence that deformation of the mechanically unusual creeping portions of the San Andreas fault system is controlled by the presence of weak minerals rather than by high fluid pressure or other proposed mechanisms. The combination of these measurements of fault core strength with borehole observations yields a self-consistent picture of the stress state of the San Andreas fault at the SAFOD site, in which the fault is intrinsically weak in an otherwise strong crust.

Talc-bearing serpentinite and the creeping section of the San Andreas fault.

The section of the San Andreas fault located between Cholame Valley and San Juan Bautista in central California creeps at a rate as high as 28 mm yr(-1) (ref. 1), and it is also the segment that yields the best evidence for being a weak fault embedded in a strong crust. Serpentinized ultramafic rocks have been associated with creeping faults in central and northern California, and serpentinite is commonly invoked as the cause of the creep and the low strength of this section of the San Andreas fault. However, the frictional strengths of serpentine minerals are too high to satisfy the limitations on fault strength, and these minerals also have the potential for unstable slip under some conditions. Here we report the discovery of talc in cuttings of serpentinite collected from the probable active trace of the San Andreas fault that was intersected during drilling of the San Andreas Fault Observatory at Depth (SAFOD) main hole in 2005. We infer that the talc is forming as a result of the reaction of serpentine minerals with silica-saturated hydrothermal fluids that migrate up the fault zone, and the talc commonly occurs in sheared serpentinite. This discovery is significant, as the frictional strength of talc at elevated temperatures is sufficiently low to meet the constraints on the shear strength of the fault, and its inherently stable sliding behaviour is consistent with fault creep. Talc may therefore provide the connection between serpentinite and creep in the San Andreas fault, if shear at depth can become localized along a talc-rich principal-slip surface within serpentinite entrained in the fault zone.