The Opioid Industry Documents Archive: Advancing Public Health Through Industry Document Disclosure.

More than twenty-five years after the first signs of potential harm, the US remains locked in the grip of an opioid epidemic, with more Americans dying from overdoses than ever before.1 Diversion of prescription opioids plays an important role in opioid-related harms. Much of the scientific and public health focus on diversion has been on end-users, given how commonly non-medical prescription opioid use occurs, as well as the proportion of individuals who report that their source of non-medical opioids was friends or family. However, diversion of opioids, as well as their rampant oversupply, can be discerned higher up the supply chain, including among wholesalers, pharmacies and rogue prescribers whose behavior may trigger well-described "flags" warranting further evaluation and action.

Inflammatory Cerebral Amyloid Angiopathy: A Broad Clinical Spectrum.

Cerebral amyloid angiopathy (CAA) is a common central nervous system (CNS) vasculopathy, which in some cases is associated with subacute encephalopathy, seizures, headaches, or strokes due to vascular inflammation directed against vascular amyloid accumulation. The pathological subtypes of inflammatory CAA include CAA-related inflammation (CAAri) with mostly perivascular lymphocytic infiltrates, or amyloid-beta (Aß)-related angiitis (ABRA) with transmural granulomatous inflammation. CAAri and ABRA probably represent part of the spectrum of CNS vasculopathies, intermediate between CAA and primary CNS vasculitis, and they are closely related to Aß-related imaging abnormalities and other manifestations of an inflammatory response directed against Aß in the leptomeninges and cerebral parenchyma. As treatment strategies in Alzheimer's disease shift toward potentially effective antiamyloid immunotherapy, the incidence rate of inflammatory CAA (which is probably an underrecognized condition) is likely to increase. Its clinical features are varied and include subacute encephalopathy, behavioral symptoms, headaches, seizures, and focal neurological deficits, which necessitate a high degree of suspicion for this disorder that often responds to treatment. The recent definition of the typical clinical and radiological syndrome has increased its recognition and may eliminate the need for invasive histological sampling in at least some affected patients. Here we review the pathophysiology, clinical spectrum, and approach to diagnosis, and discuss illustrative cases that highlight the wide range of clinical presentations.

Relationship between Thoroughbred workloads in racing and the fatigue life of equine subchondral bone.

Fatigue life (FL) is the number of cycles of load sustained by a material before failure, and is dependent on the load magnitude. For athletes, 'cycles' translates to number of strides, with load proportional to speed. To improve previous investigations estimating workload from distance, we used speed (m/s, x) per stride collected using 5 Hz GPS/800 Hz accelerometer sensors as a proxy for limb load to investigate factors associated with FL in a Thoroughbred race start model over 25,234 race starts, using a combination of mathematical and regression modelling. Fore-limb vertical force (NKg-1) was estimated using a published equation: Vertical force = 2.778 + 2.1376x - 0.0535x2. Joint load (σ) was estimated based on the vertical force, scaled according to the maximum speed and defined experimental loads for the expected variation in load distribution across a joint surface (54-90 MPa). Percentage FL (%FL) was estimated using a published equation for cycles to failure (Nf) summed across each race start: Nf = 10(σ-134.2)/-14.1. Multivariable mixed-effects linear regression models were generated on %FL, adjusting for horse-level clustering, presented as coefficients; 95%CI. Scaled to the highest joint load, individual starts accrued a mean of 9.34%FL (sd. 1.64). Older age (coef. 0.03; 0.002-0.04), longer race-distances (non-linear power transformed), and firmer track surfaces (ref. Heavy 10: Good 3 coef. 2.37; 2.26-2.48) were associated with greater %FL, and males accrued less than females (p < 0.01). Most variables associated with %FL are reported risk factors for injury. Monitoring strides in racehorses may therefore allow identification of horses at risk, enabling early detection of injury.