Epidemiology in the pharmaceutical industry

A survey assessing the practice of epidemiology in the pharmaceutical industry was sent to all member companies and research affiliates of the Pharmaceutical Research and Manufacturers of America (PhRMA) and to six non‐member companies. Eighty‐three companies were surveyed. Screening questions established whether or not a company employed epidemiologists, had an epidemiology department, or contracted work to epidemiologists outside the company. The survey included questions about organizational structure, functional role of epidemiologists, epidemiology department activities within the company, and collaboration with external partners. The response rate was 90.4%. Of the responding companies, 40% employed epidemiologists, 20% had epidemiology departments, and 36% utilized epidemiologists contracted outside the company. Eighty per cent of companies that employed epidemiologists also contracted epidemiology services outside of the company, while 6.7% of companies that did not employ epidemiologists utilized outside epidemiology services. Among all companies 42.7% employed or utilized epidemiologists. Differences were found in the extent to which large, medium and small pharmaceutical companies employ and utilize epidemiologists. The survey demonstrates that epidemiologists perform many roles within the pharmaceutical industry; that there are many potential opportunities for epidemiologists in this industry and that increased emphasis on safety will require more epidemiology training and recruitment efforts. Copyright © 2000 John Wiley & Sons, Ltd.     

Therapeutic Potential of a Novel Glucagon-like Peptide-1 Receptor Agonist,NLY01, in Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination, gliosis, and neurodegeneration. While the currently available disease-modifying therapies effectively suppress the immune attack on the CNS, there are no therapies to date that directly mitigate neurodegeneration. Glucagon-like peptide-1 (GLP-1) is a small peptide hormone that maintains glucose homeostasis. A novel GLP-1 receptor (GLP-1R) agonist, NLY01, was recently shown to have neuroprotective effects in the animal models of Parkinson’s disease and is now in a phase 2 clinical trial. In this study, we investigated the therapeutic potential of NLY01 in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our data show that NLY01 delays the onset and attenuates the severity of EAE in a prevention paradigm, when given before disease onset. NLY01 inhibits the activation of immune cells in the spleen and reduces their trafficking into the CNS. In addition, we show that NLY01 suppresses the production of chemokines that are involved in leukocyte recruitment to the site of inflammation. The anti-inflammatory effect of NLY01 at the early stage of EAE may block the expression of the genes associated with neurotoxic astrocytes in the optic nerves, thereby preventing retinal ganglion cell (RGC) loss in the progressive stage of EAE. In the therapeutic paradigm, NLY01 significantly decreases the clinical score and second attack in a model of relapsing–remitting EAE. GLP-1R agonists may have dual efficacy in MS by suppressing peripheral and CNS inflammation, thereby limiting neuronal loss.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01088-5.     

Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median–ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1748–1758, 1998     

The Fundamental Skills and Deconstructed Sub-Steps of Pediatric Cardiopulmonary Bypass

Perfusion education programs use simulation to provide students with clinical skills prior to entering the operating room. To teach the psychomotor execution of skills in a simulation lab requires a list of validated skills and deconstructed sub-steps to fully optimize adult learning. A list of the fundamental skills of adult cardiopulmonary bypass (CPB) was recently published; however, no defined list exists regarding pediatric CPB skills. The purpose of this survey is to form a definitive list of skills fundamental to pediatric CPB. A survey of 23 proposed pediatric CPB clinical skills and 291 proposed skill sub-steps was developed. Proposed pediatric CPB skills were evaluated using an established frequency and harm index. If the skill is performed >50% of the time (frequency), and if >50% believe that if the skill is performed incorrectly patient harm is probable (risk), then the skill is accepted as fundamental. The survey content was validated by subject matter experts and then distributed to practicing perfusionists between September 2020 and December 2020. Of the 125 survey respondents, 57.9% had 10 or more years in the field. 35.2% of respondents are American Society of Extracorporeal Technology (AmSECT) Fellows of Pediatric Perfusion (FPP) and pediatric CPB represents >50% of the annual caseload for 69.7% of respondents. 22 of the 23 proposed skills were accepted as fundamental in the conduct of pediatric CPB and 258 of the 291 proposed sub-steps associated with CPB skills were accepted as integral to skill performance. By surveying practicing pediatric perfusionists, this study identifies 22 skills as fundamental to the safe execution of pediatric CPB. In addition, skill sub-elements were identified as necessary for skill execution. This knowledge will assist perfusion programs in developing a pediatric simulation curriculum that matches current clinical execution of pediatric skills.     

Five myofibrillar lesion types in eccentrically challenged,unloaded rat adductor longus muscle—a test model

Sarcomere disruptions are observed in the adductor longus (AL) muscles following voluntary reloading of spaceflown and hindlimb suspension unloaded (HSU) rat, which resemble lesions in eccentrically challenged muscle. We devised and tested an eccentric contraction (ECCON) test system for the 14‐day HSU rat AL. Six to 7 hours following ECCON, ALs were fixed to allow immunostaining and electron microscopy (EM). Toluidine blue‐stained histology semithin sections were screened for lesion density (#/mm²). Serial semithin sections from the ECCON group were characterized for myosin immunointensity of lesions. Five myofibrillar lesion types were identified in histological semithin sections: focal contractions; wide A‐bands; opaque areas; missing A‐bands; and hyperstretched sarcomeres. Lesion density by type was greater for ECCON than NonECCON ALs (P ≤ 0.05; focal contractions and opaque regions). Lesion density (#‐of‐all‐five‐types/mm²) was significantly different (ECCON: 23.91 ± 10.58 vs. NonECCON: 5.48 ± 1.28, P ≤ 0.05; ECCON vs. SHAM: 0.00 ± 0.00; P ≤ 0.025). PostECCON optimal tension decreased (Poi‐drop, 17.84 ± 4.22%) and was correlated to lesion density (R² = 0.596), but prestretch tension demonstrated the highest correlation with lesion density (R² = 0.994). In lesions, the darkly staining A‐band lost the normally organized thick filament alignment to differing degrees across the different lesion types. Ranking the five lesion types by a measure of lesion length deformation (hypercontracted to hyperstretched) at the light microscopy level, related to the severity of thick filament registry loss across the lesion types at the electron microscopic level. This ranking suggested that the five lesion types seen in semithin sections at the light level represented a lesion progression sequence and paralleled myosin immunostaining loss as the distorted A‐band filaments spread across the hyperlengthening lesion types. Lesion ultrastructure indicated damage involved calcium homeostasis loss (focal contraction lesions) and “thick‐filamentcentering” failure of titin (wide A‐band lesions) in the early stages of lesion development. Anat Rec 254:39–52, 1999. © 1999 Wiley‐Liss, Inc.     

Cost of maternal near miss and potentially life-threatening conditions,Kenya

ObjectiveTo estimate the direct costs of treating women with maternal near misses and potentially life-threatening conditions in Kenya and the factors associated with catastrophic health expenditure for these women and their households.MethodsAs part of a prospective, nationally representative study of all women with near misses during pregnancy and childbirth or within 42 days of delivery or termination of pregnancy, we compared the cost of treating maternal near-miss cases admitted to referral facilities with that of women with potentially life-threatening conditions. We used logistic regression analysis to assess clinical, demographic and household factors associated with catastrophic health expenditure.FindingsOf 3025 women, 1180 (39.0%) had maternal near misses and 1845 (61.0%) had potentially life-threatening conditions. The median cost of treating maternal near misses was 7135 Kenyan shillings (71 United States dollars, US$) compared with 2690 Kenyan shillings (US$ 27) for potentially life-threatening conditions. Of the women who made out-of-pocket payments, 26.4% (122/462) experienced catastrophic expenditure. The highest median costs for treatment of near misses were in Nairobi and Central region (22 220 Kenyan shillings; US$ 222). Women with ectopic pregnancy complications and pregnancy-related infections had the highest median costs of treatment, at 7800 Kenyan shillings (US$ 78) and 3000 Kenyan shillings (US$ 30), respectively. Pregnancy-related infections, abortion, ectopic pregnancy, and treatment in secondary and tertiary facilities were significantly associated with catastrophic expenditure.ConclusionThe cost of treating maternal near misses is high and leads to catastrophic spending through out-of-pocket payments. Universal health coverage needs to be expanded to guarantee financial protection for vulnerable women.