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INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.
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Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Controle Glicêmico , Sistema de Registros , Humanos , Hong Kong/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Criança , Adolescente , Hemoglobinas Glicadas/análise , Estudos Retrospectivos , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/diagnóstico , Prevalência , Glicemia/análise , Fatores de Risco , Pré-EscolarRESUMO
AIM: Barriers to retention in inpatient and residential care for persons who use drugs are understudied in the rural context. We sought to better understand barriers to retention in inpatient and residential drug treatment in a large, multi-site, geographically diverse sample of persons who use opioids and/or injection drugs in the rural U.S. METHODS: We conducted semi-structured individual interviews with persons currently using opioids and/or injection drugs in 9 U.S. states, including Illinois, Kentucky, Massachusetts, North Carolina, New Hampshire, Ohio, Oregon, Vermont, and Wisconsin. Content areas included substance use history and experiences with all modalities of drug treatment. We performed initial structural coding followed by an iterative "open-coding" process of itemizing and categorizing content within each code, and a multi-coder memoing process to summarize themes. We identified themes using three levels of the Social-Ecological Model (SEM): individual, interpersonal, and facility-level (organizational) barriers. RESULTS: Among 304 interviewed, over half (n = 166, 54 %) reported having experienced inpatient and residential treatment. Lack of treatment retention was driven by interrelated factors at all levels of the SEM. Person-level factors inhibiting retention included lack of readiness to stop using, which was particularly true for court-ordered treatment, and dislike of "freedom limitations". The sole interpersonal-level factor was the influence of other patients on re-initiation of drug use. Facility-level barriers included unaddressed withdrawal symptoms and lack of access to MOUD, staff relatability, inadequate staff training, and, particularly in residential treatment, lack of structure and supervision. Lack of preparation for coping with real-world triggers was seen as a barrier to engagement in ongoing treatment. CONCLUSION: Barriers to retention in inpatient and residential substance use treatment were present at three levels of the SEM. Interviews suggest much room for improvement in inpatient and residential drug treatment programs with respect to improving access to MOUD, tailoring content to better address social challenges in the rural context, and improving quality control measures with respect to staff and resident supervision.
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Pacientes Internados , Transtornos Relacionados ao Uso de Opioides , Tratamento Domiciliar , População Rural , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Feminino , Adulto , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Estados Unidos , Pessoa de Meia-Idade , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/psicologia , Acessibilidade aos Serviços de SaúdeRESUMO
BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.
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Estimulantes do Sistema Nervoso Central , Overdose de Drogas , Metanfetamina , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Humanos , Masculino , Estados Unidos/epidemiologia , Adulto , Feminino , Analgésicos Opioides/uso terapêutico , Motivação , Tolerância a Medicamentos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Overdose de Drogas/epidemiologiaRESUMO
Background: People who inject drugs (PWID) are a key population for treatment with direct-acting antiviral medications (DAAs) to eliminate hepatitis C virus (HCV). We developed a Pharmacist, Physician, and Patient Navigator Collaborative Care Model (PPP-CCM) for delivery of HCV treatment; this study describes clinical outcomes related to HCV treatment (initial evaluation, treatment initiation, completion, and cure), as well as patient satisfaction. Methods: We conducted a single-arm prospective pilot study of adult PWID living with HCV. Participants completed baseline and six-month follow-up surveys, and treatment and outcomes were abstracted from electronic health records. Primary outcome was linkage to pharmacist for HCV evaluation; secondary outcomes included DAA initiation, completion, and cure, as well as patient-reported satisfaction. Results: Of the 40 PWID enrolled, mean age was 43.6 years, 12 (30 %) were female, 20 (50 %) were non-white, and 15 (38 %) were unhoused. Thirty-eight (95 %) were successfully linked to the pharmacist for initial evaluation. Of those, 21/38 (55 %) initiated DAAs, and 16/21 (76 %) completed treatment. Among those completing treatment who had viral load data to document whether they achieved "sustained virologic response", i.e. cure, 10/11 (91 %) were found to be cured. There was high satisfaction with 100 % responding "agree or strongly agree" that they had a positive experience with the pharmacist. Conclusion: Nearly all participants in this pilot were successfully linked to the pharmacist for evaluation, and more than half were started on DAAs; results provide preliminary evidence of feasibility of pharmacist-led models of HCV treatment for PWID. Clinicaltrialsgov registration number: NCT04698629.
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INTRODUCTION: Paediatric patients differ from adult patients with respect to anatomy, examination factors, behaviour, and intellectual development, requiring dedicated specialised knowledge and expertise. In the absence of a formal dedicated paediatric medical imaging subspecialty, this study undertook to understand student radiographers' experiences and perspectives on paediatric medical imaging. METHODS: The study entailed a descriptive cross-sectional survey design entailed a 51-item closed and open-ended response questionnaire using a total sampling method. Data were collected from both under- and postgraduate student radiographers who undertook clinical placement. Data interpretation and analysis involved statistical analysis of close-ended questions and thematic analysis of open-ended questions. RESULTS: The overall response rate was 70%. Most participants acknowledged the importance of dedicated paediatric content as well as the theory content covered. The shortcoming in pre-placement practical component was overcome through varied approaches like observations and attempting through supervision whilst experiencing uncertainty, anxiety and felt unfair to risk the patient. As reported in literature like their qualified counterparts expressed similar challenges in technique adaptation, styles of interactions in gaining cooperation from both the children and parents. They also felt paediatric content and the practicals should be embedded throughout the course offering to not compromise the day-to-day service delivery. CONCLUSIONS: The study findings iterate the importance paediatric imaging in the service delivery context. The importance of undertaking these examinations reliant on experiential learning is insufficient to bridge the gap of preparation prior to placement. IMPLICATIONS FOR PRACTICE: Collaborative academic and clinical radiography education will ensure that radiography students' dedicated specialised paediatric imaging knowledge and experience are enhanced.
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Radiologia , Estudantes de Medicina , Criança , Humanos , Austrália , Estudos Transversais , Radiografia , Radiologia/educaçãoRESUMO
BACKGROUND: Co-use of stimulants and opioids is rapidly increasing. Randomized clinical trials (RCTs) have established the efficacy of medications for opioid use disorder (MOUD), but stimulant use may decrease the likelihood of initiating MOUD treatment. Furthermore, trial participants may not represent "real-world" populations who would benefit from treatment. METHODS: We conducted a two-stage analysis. First, associations between stimulant use (time-varying urine drug screens for cocaine, methamphetamine, or amphetamines) and initiation of buprenorphine or extended-release naltrexone (XR-NTX) were estimated across two RCTs (CTN-0051 X:BOT and CTN-0067 CHOICES) using adjusted Cox regression models. Second, results were generalized to three target populations who would benefit from MOUD: Housed adults identifying the need for OUD treatment, as characterized by the National Survey on Drug Use and Health (NSDUH); adults entering OUD treatment, as characterized by Treatment Episodes Dataset (TEDS); and adults living in rural regions of the U.S. with high rates of injection drug use, as characterized by the Rural Opioids Initiative (ROI). Generalizability analyses adjusted for differences in demographic characteristics, substance use, housing status, and depression between RCT and target populations using inverse probability of selection weighting. RESULTS: Analyses included 673 clinical trial participants, 139 NSDUH respondents (weighted to represent 661,650 people), 71,751 TEDS treatment episodes, and 1,933 ROI participants. The majority were aged 30-49 years, male, and non-Hispanic White. In RCTs, stimulant use reduced the likelihood of MOUD initiation by 32% (adjusted HR [aHR] = 0.68, 95% CI 0.49-0.94, p = 0.019). Stimulant use associations were slightly attenuated and non-significant among housed adults needing treatment (25% reduction, aHR = 0.75, 0.48-1.18, p = 0.215) and adults entering OUD treatment (28% reduction, aHR = 0.72, 0.51-1.01, p = 0.061). The association was more pronounced, but still non-significant among rural people injecting drugs (39% reduction, aHR = 0.61, 0.35-1.06, p = 0.081). Stimulant use had a larger negative impact on XR-NTX initiation compared to buprenorphine, especially in the rural population (76% reduction, aHR = 0.24, 0.08-0.69, p = 0.008). CONCLUSIONS: Stimulant use is a barrier to buprenorphine or XR-NTX initiation in clinical trials and real-world populations that would benefit from OUD treatment. Interventions to address stimulant use among patients with OUD are urgently needed, especially among rural people injecting drugs, who already suffer from limited access to MOUD.
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Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Masculino , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologiaRESUMO
Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.
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Dor Crônica , Infecções por HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Dor Crônica/epidemiologia , ComorbidadeRESUMO
INTRODUCTION: This study aimed to assess the trend of percutaneous and open surgical procedures for peripheral arteriovenous malformations (AVMs) performed in NHS hospitals in England between 2012 and 2018. METHODS: Hospital Episode Statistics (HES) is a freely available data warehouse that represents the whole population of England served by the NHS. Data from the HES database was obtained and analysed for all hospital episodes between 2012 and 2018 for the total number and trend of 'primary diagnosis', and 'primary procedures and interventions' identified for peripheral AVMs. RESULTS: Over the period studied, there was an increase in the total number of admissions for peripheral AVMs; total primary diagnosis increased from 2242 to 2857 per year. Open surgery remained more commonly performed than percutaneous procedures throughout the studied period. However, the overall percentage of primary procedures and interventions being percutaneous in this period increased from 29.8% to 41.0% per year. The increase in the number of percutaneous procedures per year seemed to occur in both children (from 43 to 124) and adults (from 408 to 492) over the course of the study period. CONCLUSIONS: This study concluded that open surgery remained the most commonly performed primary procedure for peripheral AVMs, although there was an increasing trend for percutaneous procedures in NHS hospitals in England. The increase in the number and percentage of percutaneous procedures for peripheral AVMs was likely to have significant resource implications for the provision of care for patients with peripheral AVMs in NHS hospitals.
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Malformações Arteriovenosas , Medicina Estatal , Adulto , Criança , Humanos , Malformações Arteriovenosas/epidemiologia , Malformações Arteriovenosas/cirurgia , Hospitalização , Inglaterra/epidemiologiaRESUMO
INTRODUCTION: Opioid use disorder (OUD) is common among people in jail and is effectively treated with medications for OUD (MOUD). People with OUD may have an incomplete or inaccurate understanding of OUD and MOUD, and of how to access care. We evaluated an OUD treatment decision making (TDM) intervention to determine whether the intervention increased MOUD initiation post-release. METHODS: We conducted an observational retrospective cohort study of the TDM intervention on initiation of MOUD, individuals with records data indicating confirmed or suspected OUD incarcerated in four eligible jails were eligible to receive the intervention. Time-to-event analyses of the TDM intervention were conducted using Cox proportional hazard modeling with MOUD as the outcome. RESULTS: Cox proportional hazard modeling, with the intervention modeled as having a time-varying effect due to violation of the proportionality assumption, indicated that those receiving the TDM intervention (nâ¯=â¯568) were significantly more likely to initiate MOUD during the first month after release from jail (adjusted hazard ratio 6.27, 95 % C.I. 4.20-9.37), but not in subsequent months (AHR 1.33 95 % C.I. 0.94-1.89), adjusting for demographics, prior MOUD, or felony or gross misdemeanor arrest in the prior year compared to those not receiving the intervention (nâ¯=â¯3174). CONCLUSION: The TDM intervention was associated with a significantly higher relative hazard of starting MOUD, specifically during the first month after incarceration. However, a minority of all eligible people received any MOUD. Future research should examine ways to increase initiation on MOUD immediately after (or ideally during) incarceration.
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Terapia Comportamental/métodos , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides/psicologia , Educação de Pacientes como Assunto/métodos , Prisioneiros/psicologia , Adolescente , Adulto , Buprenorfina/uso terapêutico , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Tratamento de Substituição de Opiáceos/psicologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Prisões , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto JovemRESUMO
With Hong Kong's ageing population, advancement of medical technologies and hospital congestion, it is not uncommon for emergency physicians to encounter complicated critically ill patients in daily practice. It becomes a fundamental role of emergency physicians to initiate timely diagnostic and therapeutic interventions to save a patient's life and improve their prognosis. It is the reason a critical care service has been developed in emergency departments worldwide over the last decade. This article shares how emergency department intensivists can contribute to this novel model of care with some illustrative cases. Advanced airway and peri-intubation management, difficult mechanical ventilation, treatment of shock, circulatory arrest, and metabolic disturbances can be safely and efficiently handled in the current emergency department setting. Obstacles, barriers, and the road ahead will be discussed.
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Cuidados Críticos/normas , Serviço Hospitalar de Emergência/organização & administração , Cuidados Críticos/organização & administração , Estado Terminal/terapia , Hong Kong , Humanos , Padrões de Prática MédicaRESUMO
On March 4, 2017 at the age of 68, Sidney George Shaw (Sid) unexpectedly died from complications following surgery, only four years after retiring from the University of Bern. Trained in biochemistry at Oxford University, Sid had quickly moved into molecular pharmacology and became a key investigator in the field of enzyme biochemistry, vasoactive peptide research, and receptor signaling. Sid spent half his life in Switzerland, after moving to the University of Bern in 1984. This article, written by his friends and colleagues who knew him and worked with him during different stages of his career, summarizes his life, his passions, and his achievements in biomedical research. It also includes personal memories relating to a dear friend and outstanding scientist whose intellectual curiosity, humility, and honesty will remain an example to us all.
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Bioquímica/história , Farmacologia/história , Endotelinas/história , Inglaterra , História do Século XX , História do Século XXI , Neurofarmacologia/história , SuíçaRESUMO
Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against cancer stem cells in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.
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Neoplasias do Endométrio/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imunoglobulina G/farmacologia , Isoenzimas/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Células-Tronco Neoplásicas/metabolismo , Retinal Desidrogenase/metabolismo , Família Aldeído Desidrogenase 1 , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Isoenzimas/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos SCID , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Retinal Desidrogenase/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: The aim of this study was to compare short-term outcomes between epidural analgesia and conventional intravenous analgesia for patients undergoing laparoscopic colectomy. This paper uses a large national database to add a current perspective on trends in analgesia and the outcomes associated with two analgesia options. Our evidence augments the opinions of recent randomized controlled trials. METHODS: The University HealthSystem Consortium, an alliance of more than 300 academic and affiliate institutions, was reviewed for the time period of October 2008 through September 2014. International Classification of Disease 9th Clinical Modification codes for laparoscopic colectomy and epidural catheter placement were used. RESULTS: A total of 29,429 patients met our criteria and underwent laparoscopic colectomy during the study period. One hundred and ten (0.374%) patients had an epidural catheter placed for analgesia. Baseline patient demographics were similar for the epidural and conventional analgesia groups. Total charges were significantly higher in the epidural group ($52,998 vs. $39,277; p < 0.001). Median length of stay was longer in the epidural group (6 vs. 5 days; p < 0.001). There was no statistical difference between the epidural and conventional analgesia groups in death (0 vs. 0.03%; p = 0.999), urinary tract infection (0 vs. 0.1%; p = 0.999), ileus (11.8 vs. 13.6%; p = 0.582), or readmission rate (9.1 vs. 9.3%; p = 0.942). CONCLUSION: Compared to conventional analgesic techniques, epidural analgesia does not reduce the rate of postoperative ileus, and it is associated with increased cost and increased length of stay. Based on our data, routine use of epidural analgesia for laparoscopic colectomy cannot be justified.
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Administração Intravenosa/estatística & dados numéricos , Analgesia Epidural/estatística & dados numéricos , Analgésicos/administração & dosagem , Colectomia/estatística & dados numéricos , Manejo da Dor/métodos , Administração Intravenosa/efeitos adversos , Administração Intravenosa/economia , Adulto , Idoso , Analgesia Epidural/efeitos adversos , Analgesia Epidural/economia , Colectomia/métodos , Feminino , Preços Hospitalares/estatística & dados numéricos , Humanos , Íleus/epidemiologia , Íleus/etiologia , Laparoscopia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Manejo da Dor/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
Wound healing is a complex physiological process comprised of discrete but inter-related and overlapping stages, requiring exact timing and regulation to successfully progress, yet occurs spontaneously in response to injury. It is characterised by four phases, coagulation, inflammation, proliferation and remodelling. Each phase is predominated by particular cell types, cytokines and chemokines. The innate immune system represents the first line of defence against invading microorganisms. It is entirely encoded with the genome, and comprised of a cellular response with specificity provided by pattern recognition receptors (PRRs) such as toll-like receptors (TLRs). TLRs are activated by exogenous microbial pathogen associated molecular patterns (PAMPs), initiating an immune response through the production of pro-inflammatory cytokines and further specialist immune cell recruitment. TLRs are also activated by endogenous molecular patterns termed damage associated molecular patterns (DAMPs). These ligands, usually shielded from the immune system, act as alarm signals alerting the immune system to damage and facilitate the normal wound healing process. TLRs are expressed by cells essential to wound healing such as keratinocytes and fibroblasts, however the specific role of TLRs in this process remains controversial. This article reviews the current knowledge on the potential role of TLRs in dermal wound healing where inflammation arising from pathogenic activation of these receptors appears to play a role in chronic ulceration associated with diabetes, scar hypertrophy and skin fibrosis.
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Imunidade Inata/fisiologia , Pele/imunologia , Pele/lesões , Receptores Toll-Like/imunologia , Cicatrização/imunologia , Animais , Proliferação de Células/fisiologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Neovascularização Fisiológica/fisiologia , Pele/metabolismo , Receptores Toll-Like/metabolismoRESUMO
In the Western world, peripheral vascular disease (PVD) has a high prevalence with high morbidity and mortality. In a large percentage of these patients, lower limb amputation is still required. Studies of ischaemic skeletal muscle disclosed evidence of endogenous angiogenesis and adaptive skeletal muscle metabolic changes in response to hypoxia. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in homeostatic and inflammatory processes. More than 50 different chemokines and 20 different chemokine receptors have been cloned. The chemokine stromal-cell-derived factor-1 (SDF-1 aka CXCL12) is a constitutively expressed and inducible chemokine that regulates multiple physiological processes, including embryonic development and organ homeostasis. The biologic effects of SDF-1 are mediated by chemokine receptor CXCR4, a 352 amino acid rhodopsin-like transmembrane-specific G protein-coupled receptor (GPCR). There is evidence that the administration of SDF-1 increases blood flow and perfusion via recruitment of endothelial progenitor cells (EPCs). This review will focus on the role of the SDF-1/CXCR4 system in the pathophysiology of PVD and discuss their potential as therapeutic targets for PVD.
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BACKGROUND: Dysfunction of the nitric oxide pathway is implicated in peripheral arterial disease. Nitric oxide synthase (NOS) isoforms and NOS activity were studied in muscle from patients with critical leg ischaemia (CLI). Alterations in NOS during revascularization surgery were also assessed. METHODS: Muscle biopsies were taken from patients with CLI undergoing amputation and also from patients undergoing femorodistal bypass at the start of surgery, after arterial clamping and following reperfusion. The presence of NOS within muscle sections was confirmed using reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. NOS isoform distribution was studied by immunohistochemistry. NOS mRNA and protein levels were measured using real-time reverse transcriptase-polymerase chain reaction and western blotting. NOS activity was assessed with the citrulline assay. RESULTS: All three NOS isoforms were found in muscle, associated with muscle fibres and microvessels. NOS I and III protein expression was increased in CLI (P = 0.041). During revascularization, further ischaemia and reperfusion led to a rise in NOS III protein levels (P = 0.008). NOS activity was unchanged. CONCLUSION: Alterations in NOS I and III occurred in muscle from patients with CLI and further changes occurred during bypass surgery.
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Ponte de Artéria Coronária , Doença da Artéria Coronariana/enzimologia , Isquemia/enzimologia , Perna (Membro)/irrigação sanguínea , Músculo Esquelético/irrigação sanguínea , Óxido Nítrico Sintase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biópsia , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Isoenzimas/metabolismo , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: To examine the prevalence of cervical dystonia (CD) in the US population. METHOD: A survey consisting of relevant demographic and CD-related questions was e-mailed to 2 million people selected from the Shopper's Voice database. RESULTS: Across a census-weighted sample, 0.280% of 60,062 respondents (79% female, 92% Caucasian) reported a diagnosis of CD and 0.170% reported a diagnosis of ST, indicating possible prevalence of 0.390% of either/both diagnoses. Less than half (42.7%) of those who reported either diagnosis were receiving treatment. CONCLUSIONS: CD is potentially under-diagnosed and under-treated; approaches to increase awareness of CD and its treatments are needed.
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Torcicolo/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Vigilância da População , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To directly compare two serotypes of botulinum toxin (BoNTA and BoNTB) in cervical dystonia (CD) using a randomized, double-blind, parallel-arm study design. METHODS: Subjects with CD who had a previous response from BoNTA were randomly assigned to BoNTA or BoNTB and evaluated in a blinded fashion at baseline, 4 weeks, 8 weeks, and 2-week intervals thereafter until loss of 80% of clinical effect or completion of 20 weeks of observation. CD severity was measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and adverse events were assessed by structured interview. Statistical analysis included Wilcoxon rank sum test, log rank tests, and Kaplan-Meier survival curves for duration of effect. RESULTS: A total of 139 subjects (BoNTA, n = 74; BoNTB, n = 65) were randomized at 19 study sites. Improvement in TWSTRS score was found at 4 weeks after injection and did not differ between serotypes. Dysphagia and dry mouth were more frequent with BoNTB (dysphagia: BoNTA 19% vs BoNTB 48%, p = 0.0005; dry mouth (BoNTA 41% vs BoNTB 80%, p < 0.0001). In clinical responders, BoNT A had a modestly longer duration of benefit (BoNTA 14 weeks, BoNTB 12.1 weeks, p = 0.033). CONCLUSION: Both serotypes of botulinum toxin (BoNTA and BoNTB) had equivalent benefit in subjects with cervical dystonia at 4 weeks. BoNTA had fewer adverse events and a marginally longer duration of effect in subjects showing a clinical response.