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1.
Bioorg Med Chem Lett ; 100: 129630, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38307441

RESUMEN

A series of macrocyclic PKCθ inhibitors based on a 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one hinge binder has been studied. Different aromatic and heteroaromatic substituents have been explored in order to optimize potency, isoform selectivity as well as DMPK properties. The importance of the length of the macrocyclic linker has also been analyzed. In particular, it has been found that methyl substitutions on the linker can have a profound influence on both potency and metabolic stability. Several compounds showing very good profiles, suitable for in vivo testing, are disclosed.

2.
N Engl J Med ; 381(19): 1801-1808, 2019 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-31633894

RESUMEN

BACKGROUND: Neurodegenerative disorders have been reported in elite athletes who participated in contact sports. The incidence of neurodegenerative disease among former professional soccer players has not been well characterized. METHODS: We conducted a retrospective cohort study to compare mortality from neurodegenerative disease among 7676 former professional soccer players (identified from databases of Scottish players) with that among 23,028 controls from the general population who were matched to the players on the basis of sex, age, and degree of social deprivation. Causes of death were determined from death certificates. Data on medications dispensed for the treatment of dementia in the two cohorts were also compared. Prescription information was obtained from the national Prescribing Information System. RESULTS: Over a median of 18 years, 1180 former soccer players (15.4%) and 3807 controls (16.5%) died. All-cause mortality was lower among former players than among controls up to the age of 70 years and was higher thereafter. Mortality from ischemic heart disease was lower among former players than among controls (hazard ratio, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P = 0.02), as was mortality from lung cancer (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.001). Mortality with neurodegenerative disease listed as the primary cause was 1.7% among former soccer players and 0.5% among controls (subhazard ratio [the hazard ratio adjusted for competing risks of death from ischemic heart disease and death from any cancer], 3.45; 95% CI, 2.11 to 5.62; P<0.001). Among former players, mortality with neurodegenerative disease listed as the primary or a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer's disease (hazard ratio [former players vs. controls], 5.07; 95% CI, 2.92 to 8.82; P<0.001) and lowest among those with Parkinson's disease (hazard ratio, 2.15; 95% CI, 1.17 to 3.96; P = 0.01). Dementia-related medications were prescribed more frequently to former players than to controls (odds ratio, 4.90; 95% CI, 3.81 to 6.31; P<0.001). Mortality with neurodegenerative disease listed as the primary or a contributory cause did not differ significantly between goalkeepers and outfield players (hazard ratio, 0.73; 95% CI, 0.43 to 1.24; P = 0.24), but dementia-related medications were prescribed less frequently to goalkeepers (odds ratio, 0.41; 95% CI, 0.19 to 0.89; P = 0.02). CONCLUSIONS: In this retrospective epidemiologic analysis, mortality from neurodegenerative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players than among matched controls. Dementia-related medications were prescribed more frequently to former players than to controls. These observations need to be confirmed in prospective matched-cohort studies. (Funded by the Football Association and Professional Footballers' Association.).


Asunto(s)
Atletas , Enfermedades Neurodegenerativas/mortalidad , Fútbol , Adulto , Anciano , Anciano de 80 o más Años , Lesiones Encefálicas , Estudios de Casos y Controles , Causas de Muerte , Femenino , Cardiopatías/mortalidad , Humanos , Incidencia , Modelos Logísticos , Longevidad , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Nootrópicos/uso terapéutico , Estudios Retrospectivos , Escocia/epidemiología
3.
J Neurol Neurosurg Psychiatry ; 93(12): 1262-1268, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36195436

RESUMEN

BACKGROUND: Autopsy studies of former contact sports athletes, including soccer and rugby players, frequently report chronic traumatic encephalopathy, a neurodegenerative pathology associated with traumatic brain injury. Nevertheless, little is known about the risk of neurodegenerative disease in these populations. We hypothesised that neurodegenerative disease risk would be higher among former elite rugby union players than the general population. METHODS: We conducted a retrospective cohort study accessing national electronic records on death certification, hospital admissions and dispensed prescriptions for a cohort of 412 male Scottish former international rugby union players and 1236 members of the general population, matched to former players by age, sex and area socioeconomic status. Mortality and incident neurodegenerative disease diagnoses among former rugby players were then compared with the matched comparison group. RESULTS: Over a median 32 years follow-up from study entry at age 30 years, 121 (29.4%) former rugby players and 381 (30.8%) of the matched comparison group died. All-cause mortality was lower among former rugby players until 70 years of age with no difference thereafter. During follow-up, 47 (11.4%) former rugby players and 67 (5.4%) of the comparison group were diagnosed with incident neurodegenerative disease (HR 2.67, 95% CI 1.67 to 4.27, p<0.001). CONCLUSIONS: This study adds to our understanding of the association between contact sports participation and the risk of neurodegenerative disease. While further research exploring this interaction is required, in the meantime strategies to reduce exposure to head impacts and head injuries in sport should be promoted.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Fútbol Americano , Enfermedades Neurodegenerativas , Humanos , Masculino , Adulto , Fútbol Americano/lesiones , Traumatismos en Atletas/epidemiología , Enfermedades Neurodegenerativas/epidemiología , Estudios Retrospectivos , Rugby , Conmoción Encefálica/diagnóstico
4.
Br J Sports Med ; 56(2): 68-79, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33619127

RESUMEN

The cessation of amateur and recreational sport has had significant implications globally, impacting economic, social and health facets of population well-being. As a result, there is pressure to resume sport at all levels. The ongoing prevalence of SARS-CoV-2 and subsequent 'second waves' require urgent best practice guidelines to be developed to return recreational (non-elite) sports as quickly as possible while prioritising the well-being of the participants and support staff.This guidance document describes the need for such advice and the process of collating available evidence. Expert opinion is integrated into this document to provide uniform and pragmatic recommendations, thereby optimising on-field and field-side safety for all involved persons, including coaches, first responders and participants.The nature of SARS-CoV-2 transmission means that the use of some procedures performed during emergency care and resuscitation could potentially be hazardous, necessitating the need for guidance on the use of personal protective equipment, the allocation of predetermined areas to manage potentially infective cases and the governance and audit of the process.


Asunto(s)
COVID-19 , Pandemias , Consenso , Primeros Auxilios , Humanos , SARS-CoV-2
5.
J Neurol Neurosurg Psychiatry ; 91(12): 1256-1260, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32694163

RESUMEN

INTRODUCTION: There is growing recognition of an association between contact sports participation and increased risk of neurodegenerative disease, including Alzheimer's disease and chronic traumatic encephalopathy. In addition to cognitive impairment, a range of mental health disorders and suicidality are proposed as diagnostic features of traumatic encephalopathy syndrome, the putative clinical syndrome associated with chronic traumatic encephalopathy. However, to date, epidemiological data on contact sport participation and mental health outcomes are limited. METHODS: For a cohort of former professional soccer players (n=7676) with known high neurodegenerative mortality and their matched general population controls (n=23 028), data on mental health outcomes were obtained by individual-level record linkage to national electronic records of hospital admissions and death certification. RESULTS: Compared with matched population controls, former professional soccer players showed lower risk of hospital admission for anxiety and stress related disorders, depression, drug use disorders, alcohol use disorders and bipolar and affective mood disorders. Among soccer players, there was no significant difference in risk of hospitalisation for mental health disorders between outfield players and goalkeepers. There was no significant difference in rate of death by suicide between soccer players and controls. CONCLUSIONS: Among a population of former professional soccer players with known high neurodegenerative disease mortality, hospital admissions for common mental health disorders were lower than population controls, with no difference in suicide. Our data provide support for the reappraisal of currently proposed diagnostic clinical criteria for traumatic encephalopathy syndrome, in particular the inclusion of mental health outcomes.


Asunto(s)
Atletas/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Trastornos Mentales/epidemiología , Fútbol , Suicidio/estadística & datos numéricos , Adulto , Anciano , Alcoholismo/epidemiología , Trastornos de Ansiedad/epidemiología , Atletas/psicología , Trastorno Bipolar/epidemiología , Estudios de Cohortes , Trastorno Depresivo/epidemiología , Humanos , Masculino , Trastornos Mentales/psicología , Salud Mental , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/epidemiología
6.
Br J Sports Med ; 2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33361278

RESUMEN

The COVID-19 pandemic has necessitated many novel responses in healthcare including sport and exercise medicine. The cessation of elite sport almost globally has had significant economic implications and resulted in pressure to resume sport in very controlled conditions. This includes protecting pitch-side medical staff and players from infection. The ongoing prevalence of SARS-CoV-2 and the desire to resume professional sport required urgent best practice guidelines to be developed so that sport could be resumed as safely as possible. This set of best practice recommendations assembles early evidence for managing SARS-CoV-2 and integrates expert opinion to provide a uniform and pragmatic approach to enhance on-field and pitch-side safety for the clinician and player. The nature of SARS-CoV-2 transmission creates new hazards during resuscitation and emergency care and procedures. Recommendations for the use and type of personal protective equipment during on-field or pitch-side emergency medical care is provided based on the clinical scenario and projected risk of viral transmission.

7.
Bioorg Med Chem Lett ; 28(17): 2998-3003, 2018 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-30122228

RESUMEN

According to the World Health Organization (WHO), approximately 1.7 million deaths per year are caused by tuberculosis infections. Furthermore, it has been predicted that, by 2050, antibacterial resistance will be the cause of approximately 10 million deaths annually if the issue is not tackled. As a result, novel approaches to treating broad-spectrum bacterial infections are of vital importance. During the course of our wider efforts to discover unique methods of targeting multidrug-resistant (MDR) pathogens, we identified a novel series of amide-linked pyrimido[4,5-b]indol-8-amine inhibitors of bacterial type II topoisomerases. Compounds from the series were highly potent against gram-positive bacteria and mycobacteria, with excellent potency being retained against a panel of relevant Mycobacterium tuberculosis drug-resistant clinical isolates.


Asunto(s)
Antibacterianos/farmacología , Girasa de ADN/metabolismo , Diseño de Fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Inhibidores de Topoisomerasa II/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Bacterias Grampositivas/metabolismo , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II/síntesis química , Inhibidores de Topoisomerasa II/química
9.
Bioorg Med Chem Lett ; 27(12): 2721-2726, 2017 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-28501511

RESUMEN

Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity. These highly selective IRAK4 compounds show activity in vivo via oral dosing in a TLR7 driven model of inflammation.


Asunto(s)
Inflamación/tratamiento farmacológico , Quinasas Asociadas a Receptores de Interleucina-1/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Administración Oral , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ensayos Analíticos de Alto Rendimiento , Imidazoles/farmacología , Inflamación/enzimología , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Interleucina-6/antagonistas & inhibidores , Interleucina-6/biosíntesis , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/química , Quinazolinas/administración & dosificación , Quinazolinas/química , Ratas , Ratas Endogámicas Lew , Relación Estructura-Actividad
10.
Bioorg Med Chem Lett ; 26(17): 4179-83, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27499455

RESUMEN

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.


Asunto(s)
Antibacterianos/química , ADN-Topoisomerasas de Tipo II/metabolismo , Tiazoles/química , Tiazolidinas/química , Inhibidores de Topoisomerasa II/química , Antibacterianos/síntesis química , Antibacterianos/farmacología , Supervivencia Celular/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/química , Evaluación Preclínica de Medicamentos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/farmacología , Tiazolidinas/síntesis química , Tiazolidinas/farmacología , Inhibidores de Topoisomerasa II/síntesis química , Inhibidores de Topoisomerasa II/farmacología
11.
Bioorg Med Chem Lett ; 25(22): 5384-8, 2015 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-26403930

RESUMEN

IRAK4 plays a critical role in the IL-1R and TLR signalling, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of permeable N-(1H-pyrazol-4-yl)carboxamides was developed by introducing lipophilic bicyclic cores in place of the polar pyrazolopyrimidine core of 5-amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamides. Replacement of the pyrazolo[1,5-a]pyrimidine core with the pyrrolo[2,1-f][1,2,4]triazine, the pyrrolo[1,2-b]pyridazine, and thieno[2,3-b]pyrazine cores guided by cLogD led to the identification of highly permeable IRAK4 inhibitors with excellent potency and kinase selectivity.


Asunto(s)
Amidas/síntesis química , Amidas/farmacología , Ácidos Carboxílicos/química , Quinasas Asociadas a Receptores de Interleucina-1/antagonistas & inhibidores , Pirazoles/química , Amidas/química , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/farmacología , Ciclización , Activación Enzimática/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Pirazoles/síntesis química , Pirazoles/farmacología
12.
Skeletal Radiol ; 44(10): 1477-83, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26109243

RESUMEN

BACKGROUND: Medical services at the Glasgow 2014 Commonwealth Games (CWG) were provided though a purpose-built medical polyclinic, which had a fully equipped radiology department along with other services, set up within the main Games Village. Data analysis of radiology services offered at CWG has not been published before. SETTING: Imaging services within the polyclinic, Athletes Village, Glasgow 2014 CWG. AIM: The aim of the paper is to analyse data on radiological investigations and assess the demand and distribution of workload on imaging services at CWG 2014. METHODOLOGY: Data on radiology investigations at the CWG 2014 was retrieved from the Carestream picture archiving and communication system (PACS) and Pharmasys (CWG official centralised electronic database system) and analysed. RESULTS: Six hundred ninety-seven diagnostic and interventional procedures were performed. Of these 37.9% were magnetic resonance imaging (MRI) scans, 22% were diagnostic ultrasound (US) examinations, 33.1% were radiographs, 4.3% were computed tomography (CT) scans and 2.7% were imaging-guided interventional procedures. 88% of imaging was performed on athletes and the remainder were performed on team officials and workforce. Demand on radiology services gradually picked up through the pre-competition period and peaked half way through the CWG. CONCLUSIONS: Radiology played a vital role in the successful provision of medical services at the Glasgow 2014 CWG. High demand on imaging services can be expected at major international sporting events and therefore pre-event planning is vital. Having back-up facilities in case of technical failure should be given due importance when planning radiology services at future CWG events.


Asunto(s)
Traumatismos en Atletas/diagnóstico , Sistemas de Información Radiológica/estadística & datos numéricos , Radiología/métodos , Radiología/estadística & datos numéricos , Traumatismos en Atletas/terapia , Humanos , Imagen por Resonancia Magnética , Radiografía Intervencional/métodos , Radiografía Intervencional/estadística & datos numéricos , Escocia , Deportes/estadística & datos numéricos , Tomografía Computarizada por Rayos X , Carga de Trabajo
13.
Biochemistry ; 53(4): 725-34, 2014 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-24450491

RESUMEN

Histone deacetylases (HDACs) play diverse roles in many diseases including cancer, sarcopenia, and Alzheimer's. Different isoforms of HDACs appear to play disparate roles in the cell and are associated with specific diseases; as such, a substantial effort has been made to develop isoform-selective HDAC inhibitors. Our group focused on developing HDAC1/HDAC2-specific inhibitors as a cancer therapeutic. In the course of characterizing the mechanism of inhibition of a novel HDAC1/2-selective inhibitor, it was determined that it did not exhibit classical Michaelis-Menten kinetic behavior; this result is in contrast to the seminal HDAC inhibitor SAHA. Enzymatic assays, along with a newly developed binding assay, were used to determine the rates of binding and the affinities of both the HDAC1/2-selective inhibitor and SAHA. The mechanism of action studies identified a potential conformational change required for optimal binding by the selective inhibitor. A model of this putative conformational change is proposed.


Asunto(s)
Antineoplásicos/química , Benzoatos/química , Histona Desacetilasa 1/antagonistas & inhibidores , Histona Desacetilasa 2/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/química , Ácidos Hidroxámicos/química , Xantenos/química , Animales , Antineoplásicos/farmacología , Benzoatos/farmacología , Línea Celular Tumoral , Femenino , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Xenoinjertos , Histona Desacetilasa 1/química , Histona Desacetilasa 2/química , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ácidos Hidroxámicos/farmacología , Cinética , Ratones , Ratones Desnudos , Modelos Moleculares , Unión Proteica , Conformación Proteica , Especificidad por Sustrato , Vorinostat , Xantenos/farmacología
14.
Pain Physician ; 27(3): 149-159, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38506682

RESUMEN

BACKGROUND: The central nervous system contains steroid receptors, particularly in the hypothalamic and limbic systems. These systems are responsible for driving certain emotions in humans, especially stress, anxiety, motivation, energy levels, and mood. Thus, corticosteroids may precipitate patients to experience these emotions. Most existing studies report neuropsychiatric side effects after oral or intravenous corticosteroids rather than epidural. OBJECTIVES: This study examines the neuropsychiatric side effects after epidural steroid injections (ESIs), with a focus on whether certain factors in patients' histories further exacerbate symptomatology. STUDY DESIGN: Prospective observational cohort study. SETTING: Fluoroscopy suite at an urban academic teaching hospital. METHODS: Patients were called 24 hours and one week after their ESIs and asked if they experienced certain neuropsychiatric symptoms more than usual compared to baseline. PATIENTS: Seventy-four patients undergoing a lumbosacral ESI (interlaminar (ILESI), caudal or transforaminal (TFESI)) were invited to take part in the study the day of his or her procedure. INTERVENTION/MEASUREMENT: Assessed whether psychiatric history, gender, race, type of ESI, or the number of levels injected affected frequency and duration of neuropsychiatric symptoms at one day and one week after an ESI. RESULTS: Significantly (P < 0.05) more patients with a psychiatric history experienced restlessness and irritability at day one than those without a psychiatric history. At week one, male gender (IRR 2.29, 95% CI 1.37, 3.83, P = 0.002), ILESI (IRR 7.75, 95% CI 1.03, 58.6, P = 0.047), and 2-level injections (IRR 2.14, 95% CI 1.13, 4.06, P = 0.019) were significantly associated to more total symptoms. LIMITATIONS: Single center study, reliance on subjective responses from patients, lack of follow-up after one week post-ESI. CONCLUSION(S): This study demonstrates that neuropsychiatric symptoms are rare overall after an ESI, though certain factors may influence patients experiencing these symptoms. Restlessness and irritability were more likely to occur one day after an ESI in those with a psychiatric history. Those who had a 2-level injection were more likely to keep experiencing most symptoms by week one, suggesting a possible correlation between corticosteroid dose and neuropsychiatric symptoms.


Asunto(s)
Ansiedad , Agitación Psicomotora , Humanos , Femenino , Masculino , Estudios Prospectivos , Corticoesteroides , Esteroides
15.
Pain Physician ; 27(2): E263-E267, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38324792

RESUMEN

BACKGROUND: Since electronic cigarettes (E-Cigs) were introduced to the United States (US) in 2007 its use has increased. Like other tobacco products, E-Cigs too pose health risks. Studies have shown a correlation between pain and tobacco use, with the association being bidirectional. However, there is limited data on the effect of E-Cig use on chronic pain, as well as its association with opioid use. OBJECTIVES: To evaluate the use of tobacco products, including E-Cigs in a chronic pain population. STUDY DESIGN: This study was designed as a cross sectional survey. SETTING: This study was set in an urban academic teaching center. METHODS: After IRB approval, surveys of established chronic pain patients were conducted over 4 months. The survey and results were anonymous, without the collection of any identifiable information. The adult patients who had been treated in the pain practice for over 3 months were included in this study. The survey collected the patients' age, gender, history of tobacco usage, cigarette smoking, E-Cig and opioid use. RESULTS: A total of 312 patients were surveyed. 198 women (63.5%) and 114 men (36.5%). The average age was 58.2; ~59 years for men and ~58 years for women. Eighty-four patients (26.9%) were managing pain using chronic opioids; 46 women and 38 men. Nine women (4.5%) had tried E-Cigs in the past, but none (0%) were active users. Eighteen men (15.8%) had tried E-Cigs in the past with 9 (7.8%) being active users. Among the opioid managed patients, 6 (9.1%) had and were active users of E-Cigs and all 6 were men (20%). LIMITATIONS: The anonymous results collected through the survey may not be accurate as they cannot be validated. In addition to the small sample size, the entire study population is from an urban academic center which may not be generalizable to all chronic pain patients. Finally, the study does not evaluate the impact of tobacco or E-Cig use on pain level or functional status. CONCLUSION: In this study of chronic pain patients, cigarette smoking and E-Cig use was similar to the reported use in the general adult population in the US. The study showed a strong correlation between tobacco use, especially cigarettes and E-Cigs, and opioid use. As the use of E-Cigs becomes more mainstream, the association between E-Cig use, chronic pain, and opioid use should be monitored.


Asunto(s)
Dolor Crónico , Sistemas Electrónicos de Liberación de Nicotina , Vapeo , Humanos , Adulto , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Dolor Crónico/epidemiología , Estudios Transversales , Analgésicos Opioides/uso terapéutico
16.
Phys Sportsmed ; 51(3): 260-268, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35191360

RESUMEN

BACKGROUND: Lower limb injuries constitute a problem in the sport of football. Our aim is to explore patterns and trends of lower limb injuries in an English professional football club. METHODS: This is a descriptive epidemiological study. Reports provided by the club's physical therapy team were screened for injuries among professional football players sustained over four seasons, from 2015/2016 to 2018/2019. Data included setting of injury (in-match or training), anatomical location of injury, type of injury, number of days off and month of injury. RESULTS: A total of 296 lower limb injuries were recorded in our study, with a rate of 11.14 per 1000 football hours. Injury rate during games was 51.38 per 1000 football hours, significantly greater than that during training at 3.81 per 1000 football hours (p = 0.021). The thigh was significantly the most commonly injured location at 4.67 per 1000 football hours (p < 0.001). Grade I tears were the most common injury type at 1.73 per 1000 football hours, significantly greater than grade III tears (p = 0.027), contusions (p = 0.043), fractures (p = 0.02), and lacerations (p = 0.019). Injury rates were found to be greatest during preseason and declined as season progressed. On average, an injury sidelined the affected footballer for a total of 20 days. CONCLUSION: Lower limb injuries were more common during matches than training. The thigh is the most common injury location, and grade I muscle tear was the most common type of injury. Injury rates were higher early on in the season. Potential prevention strategies include spacing out competition, adopting training and exercise regimens that cater for recovery, and increasing research regarding injury mechanisms.


Asunto(s)
Traumatismos en Atletas , Fútbol , Esguinces y Distensiones , Humanos , Incidencia , Extremidad Inferior/lesiones , Fútbol/lesiones
17.
Urol Pract ; 9(5): 474-480, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37145725

RESUMEN

INTRODUCTION: COVID-19 has forever impacted health care in the U.S. Changes to health and hospital policies led to disruptions to both patient care and medical training. There is limited understanding of the impact on urology resident training across the U.S. Our aim was to examine trends in urological procedures, as captured by the Accreditation Council for Graduate Medical Education resident case logs, throughout the COVID-19 pandemic. METHODS: Retrospective review of publicly available urology resident case logs between July 2015 and June 2021 was performed. Average case numbers were analyzed via linear regression with different models specifying different assumptions regarding the impact of COVID-19 on procedure in 2020 and onward. Statistical calculations utilized R (version 4.0.2). RESULTS: Analysis favored models which assumed the impact of COVID-related disruptions were specific to 2019-2020. Analysis of procedures performed indicate an average upward trend of urology cases nationally. An average annual increase of 26 procedures between 2016 and 2021 was noted, except for 2020 which saw an average drop of approximately 67 cases. However, in 2021 case volume dramatically increased to the same rate as projected had there not been a disruption in 2020. Stratifying by category of urology procedure revealed evidence for variability between categories in the magnitude of the 2020 decrease. CONCLUSIONS: Despite widespread pandemic-related disruptions in surgical care, urological volume has rebounded and increased, likely having minimal detriment to urological training over time. Urological care is essential and in high demand as evidenced by the uptick in volume across the U.S.

19.
Bioorg Med Chem Lett ; 21(8): 2559-63, 2011 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-21435873

RESUMEN

Optimization of a water soluble, moderately potent lead series of isoxazole-3-carboxamides was conducted, affording a compound with the requisite balance of potency, solubility and physicochemical properties for in vivo use. Compound 8e was demonstrated to be efficacious in a rat model of inflammatory pain, following oral administration.


Asunto(s)
Isoxazoles/química , Canales Catiónicos TRPV/antagonistas & inhibidores , Administración Oral , Amidas/síntesis química , Amidas/química , Amidas/uso terapéutico , Animales , Modelos Animales de Enfermedad , Humanos , Isoxazoles/síntesis química , Isoxazoles/uso terapéutico , Dolor/tratamiento farmacológico , Ratas , Canales Catiónicos TRPV/metabolismo
20.
Bioorg Med Chem Lett ; 21(15): 4652-7, 2011 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-21723725

RESUMEN

Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration.


Asunto(s)
Ciclohexanoles/química , Isoxazoles/química , Canales Catiónicos TRPV/antagonistas & inhibidores , Administración Oral , Amidas/química , Amidas/farmacocinética , Amidas/uso terapéutico , Animales , Capsaicina/toxicidad , Ciclohexanoles/farmacocinética , Ciclohexanoles/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Isoxazoles/farmacocinética , Isoxazoles/uso terapéutico , Microsomas Hepáticos/metabolismo , Ratas , Relación Estructura-Actividad , Canales Catiónicos TRPV/metabolismo
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