RESUMO
Insight regarding the impact of COVID-19 on return to sporting participation is a key issue for many athletes. We report time-loss following respiratory tract infection (RTI), over the pandemic, in UK athletes preparing for international competition. During the study, 566 athletes developed COVID-19 and 217 developed other causes of RTI. Time-loss from COVID-19 reduced from a median (interquartile range) of 27 days (13- 40) in April-June 2020 to 10 days (8-13) from October-December 2022 (P<0.001). There was no change in time-loss following RTi (P=0.13). The time-loss period following COVID-19 has shortened over the pandemic. Further work is needed to explore why some athletes still have prolonged sporting time-loss.
Assuntos
COVID-19 , Infecções Respiratórias , Esportes , Humanos , COVID-19/epidemiologia , AtletasRESUMO
Deep neuromuscular block aims to improve operative conditions during laparoscopic surgery with a lower intra-abdominal pressure. Studies are conflicting on whether meaningful improvements in quality of recovery occur beyond emergence, and whether lower intra-abdominal pressure is achieved. In this pragmatic randomised trial with 1:1 allocation, adults undergoing elective laparoscopic surgery were allocated to moderate neuromuscular block reversed with neostigmine, or deep neuromuscular block reversed with sugammadex. Allocation was revealed to the anaesthetist only. Primary outcome was cognitive recovery of the Postoperative Quality of Recovery Scale, 7 days after surgery. Secondary outcomes included recovery in other domains of the Postoperative Quality of Recovery Scale at 15 min and 40 min; days 1, 3, 7, 14; and 1 and 3 months after surgery. Chi-square test was used for the primary outcome, and generalised linear mixed model for recovery over time between groups. Of 350 participants randomised, 140 (deep) and 144 (moderate) were analysed for the primary outcome. There was no difference in the Postoperative Quality of Recovery Scale cognitive domain at day 7 (deep 92.9% vs. moderate 91.8%, OR 1.164; 95%CI 0.486-2.788, p = 0.826), or at any other time-point. No significant difference was observed for physiological, emotive, activities of daily living, nociception, or overall recovery. Length of stay in the recovery area (mean (SD) deep 108 (58) vs. moderate 109 (57) min, p = 0.78) and hospital (1.8 (1.9) vs. 2.6 (3.5) days, p = 0.019) was not different. Intra-abdominal pressure and surgical operating conditions were not different between groups. Deep neuromuscular block did not improve quality of recovery compared with moderate neuromuscular block in operative laparoscopic surgery over a 1-h duration.
Assuntos
Período de Recuperação da Anestesia , Inibidores da Colinesterase/uso terapêutico , Neostigmina/uso terapêutico , Bloqueio Neuromuscular/métodos , Sugammadex/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Estudos Prospectivos , Método Simples-CegoRESUMO
Zonal flow appears in toroidal, magnetically confined plasmas as part of the self-regulated interaction of turbulence and transport processes. For toroidal plasmas having a strong toroidal magnetic field, the zonal flow is predominately poloidally directed. This Letter reports the first observation of a zonal flow that is toroidally directed. The measurements are made just inside the last closed flux surface of reversed field pinch plasmas that have a dominant poloidal magnetic field. A limit cycle oscillation between the strength of the zonal flow and the amplitude of plasma potential fluctuations is observed, which provides evidence for the self-regulation characteristic of drift-wave-type plasma turbulence. The measurements help advance understanding and gyrokinetic modeling of toroidal plasmas in the pursuit of fusion energy.
RESUMO
The first direct measurements of an impurity particle flux driven by drift-wave turbulence in a toroidal magnetized plasma are reported. The correlation between the impurity density and radial velocity fluctuations is measured using ion Doppler spectroscopy. The small, very fast radial velocity fluctuation is resolved with the aid of a new linearized spectrum correlation analysis method that rejects uncorrelated noise as the sample size increases. The measured C^{2+} turbulent impurity flux in the edge of the plasma is directed inward and is consistent with impurity density measurements. This is also the first direct evidence for fluctuation-induced transport due to trapped-electron-mode turbulence in reversed field pinch plasmas.
RESUMO
PURPOSE: Given the difficulty of durable repairs, there is continued interest in hernia prevention. One emerging prevention technique for parastomal hernias is prophylactic mesh placement, whereby mesh is inserted during the index procedure as hernia prophylaxis. We evaluated our experience using prophylactic mesh when creating an ileal conduit. METHODS: We retrospectively reviewed patients undergoing robotic cystectomy with ileal conduit from 6/2010 to 8/2017. Patient demographics and operative/perioperative outcomes were documented. We evaluated hernia recurrence using postoperative computed tomography scanning or physical exam. Prophylactic mesh was inserted at the operating surgeon's discretion using a synthetic resorbable or biologic mesh. RESULTS: During the study period, 38 patients underwent robotic-assisted cystectomy with ileal conduit formation. Average patient age was 68 years, with 28 (74%) male and 35 (92%) Caucasian patients. Three patients (8%) required conversion to open, and one patient (3%) had a concomitant colorectal resection. Thirty-one (88%) patients had postoperative computed tomography scanning. Prophylactic mesh was used in 18 patients (47%) in a retrorectus position. Of these, 15 (83%) patients had synthetic resorbable mesh and 3 (17%) patients had biologic mesh. At average follow-up of 21 months, one hernia recurred (5%) in a patient without mesh placement at the time of ileal conduit. At an average follow-up of 11 months, there have been no recurrences and no mesh-related complications in the prophylactic mesh group. CONCLUSIONS: Using prophylactic mesh in ileal conduit, creation is feasible and may decrease the parastomal hernia formation rate. Further study of using synthetic resorbable and biologic meshes for hernia prophylaxis is warranted.
Assuntos
Cistectomia , Hérnia Ventral/prevenção & controle , Telas Cirúrgicas , Derivação Urinária , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Estomas CirúrgicosRESUMO
While mutations in the fragile X mental retardation-1 (FMR1) gene are associated with varying reproductive outcomes in females, the effects of a complete lack of FMR1 expression are not known. Here, we studied the ovarian and reproductive phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were obtained at multiple time points in KO and wild type (WT) mice fed a control or rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian reserve than WT mice with an increased proportion of activated follicles. mTOR and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO mice, and increased the primordial follicle pool and age of last litter in WT mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO mice and proposes that premature recruitment of the primordial pool via altered mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in rapamycin-treated KO mice, as well as increased reproductive lifespan of rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic target.
Assuntos
Proteína do X Frágil da Deficiência Intelectual/genética , Oócitos/metabolismo , Reserva Ovariana/efeitos dos fármacos , Sirolimo/administração & dosagem , Serina-Treonina Quinases TOR/metabolismo , Animais , Feminino , Camundongos , Camundongos Knockout , Oócitos/efeitos dos fármacos , Tamanho do Órgão , Folículo Ovariano/efeitos dos fármacos , Fenótipo , Fosforilação , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologiaRESUMO
PURPOSE: To evaluate abdominal wall closure knowledge base and technical skills in surgical and OB/GYN residents. METHODS: Residents consented to participate in a skills laboratory and quiz. The skills portion involved closure of a 10-cm incision on a simulated abdominal wall. Participants were timed, filmed, and graded using a standardized grading system. RESULTS: Thirty surgical and OB/GYN residents participated. All residents reported closing the abdominal wall continuously, 97% preferred slowly absorbing sutures (28/29), 97% preferred taking 1-cm bites (29/30), and 93% spaced bites 1 cm apart (27/29). However, 77% (10/13) of surgery residents identified 4:1 as the ideal suture to wound length ratio; 47% (7/15) of OB/GYN residents believed it to be 2:1, and another 40% (6/15) indicated 3:1 (p < 0.0001). In the simulation, OB/GYN residents used significantly fewer stitches (p = 0.0028), significantly more distance between bites (p < 0.0001), and significantly larger bite size (p < 0.0001) than surgery residents. When graded, there was no significant difference between programs. CONCLUSIONS: Despite some knowledge regarding the principles of abdominal wall closure among surgical and OB/GYN residents, more instruction is needed. We identified some differences in knowledge base and techniques for abdominal wall closure among general surgery and OB/GYN residents, which are likely due to differences in educational curriculums.
Assuntos
Técnicas de Fechamento de Ferimentos Abdominais/educação , Competência Clínica , Cirurgia Geral/educação , Ginecologia/educação , Internato e Residência , Parede Abdominal/cirurgia , Currículo , Humanos , SuturasRESUMO
PURPOSE: Research has established that a ≥4:1 suture to wound (S:W) length ratio decreases incisional hernias. We evaluated our ability to obtain a 4:1 S:W length ratio in a surgery residency program. METHODS: Consecutive abdominal wall closures from 12/1/2013 through 4/9/2015 were reviewed. The length of the incisions and amount of suture used were measured. Patient demographics and operative variables were documented and compared related to inability to obtain a 4:1 ratio. RESULTS: One hundred patients underwent abdominal closure with S:W length measurements. Average wound length was 18.3 cm; average suture length used was 84.5 cm; and average S:W length ratio was 4.6:1. An S:W length ratio of ≥4:1 was achieved in 76% of cases. There was no difference in race, age, gender, BMI, type of procedure, or resident level in obtaining a 4:1 S:W length ratio. There was a significantly higher rate of not achieving a 4:1 ratio when two residents closed. Postoperative infection rate and hernia rate increased when a 4:1 S:W length ratio was not achieved compared with an adequate S:W length ratio. CONCLUSIONS: Despite the known importance of achieving a 4:1 S:W length ratio for abdominal closure, it was only achieved in 76% of study patients. Improved education on the importance of fascial closure is needed.
Assuntos
Técnicas de Fechamento de Ferimentos Abdominais/instrumentação , Hérnia Incisional/prevenção & controle , Laparotomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Ferida Cirúrgica/patologia , Suturas , Parede Abdominal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Hérnia Incisional/epidemiologia , Internato e Residência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
The field of abdominal wall hernia surgery continues to evolve at a rapid pace. Surgeons dealing with abdominal wall hernias must constantly stay abreast as new biomaterials and surgical techniques evolve. Increasing knowledge related to hernia formation and factors affecting outcomes will help surgeons prevent hernias and individualize hernia repair techniques and biomaterials based on specific clinical situations and patient characteristics. This review outlines some new advances in abdominal wall hernia management focusing on hernia prevention, preoperative strategies to improve outcomes, available biomaterials and mesh products used in hernia repair, new surgical techniques, and improving ways to evaluate outcomes and perform continuous quality improvement in hernia repair.
Assuntos
Parede Abdominal/cirurgia , Hérnia Ventral/cirurgia , Herniorrafia , Telas Cirúrgicas , Herniorrafia/métodos , Humanos , Técnicas de Sutura , Resultado do TratamentoRESUMO
BACKGROUND: Initial validation and feasibility for the Post-operative Quality of Recovery Scale (PQRS) was published in 2010. Ongoing validation includes studies to determine whether this scale can discriminate differences in recovery between cohorts. METHODS: A prospective cohort study included 61 patients, 18-40 years, and 61 patients, aged ≥ 65 years, undergoing knee arthroscopy under general anaesthesia; and 13 patients, aged ≥ 65 years, undergoing total knee replacement under general anaesthesia. Patients were assessed using the PQRS. Assessments were performed pre-surgery, at 15 and 40 min, 1 and 3 days, and 3 months after surgery. RESULTS: The effect of age was assessed by comparing young versus older arthroscopy patients. There were minimal differences in recovery profiles, other than for the nociceptive domain, where pain recovery was significantly better in the older arthroscopy patients (P < 0.001). The effect of surgery was assessed by comparing older patients undergoing knee arthroscopy with knee replacement patients. Recovery was significantly worse for the knee replacement group for cognition (P = 0.015), nociception (pain and nausea, P < 0.001), activities of daily living (P < 0.001), emotive recovery (P = 0.029), and all-domains recovery (P < 0.001). Despite differences in quality of recovery, satisfaction was high in all cohorts. CONCLUSIONS: Knee replacement had a large effect on recovery compared with knee arthroscopy. Age had minimal effect on recovery after knee arthroscopy. The study showed the ability of the PQRS to discriminate recovery in different domains.
Assuntos
Artroplastia do Joelho , Artroscopia , Articulação do Joelho/cirurgia , Recuperação de Função Fisiológica , Atividades Cotidianas , Adolescente , Adulto , Fatores Etários , Idoso , Anestesia Geral/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/estatística & dados numéricos , Artroscopia/efeitos adversos , Artroscopia/estatística & dados numéricos , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Resultado do Tratamento , Vitória/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Initial validation and feasibility of the Post-Operative Quality of Recovery Scale (PQRS) was published in 2010. Ongoing validation includes studies to determine whether this scale can discriminate differences in recovery in similar patients having different surgery. METHODS: A prospective observational study included 89 patients undergoing nasal surgery and 46 patients undergoing tonsillectomy as the primary surgical procedure. Patients were assessed using the PQRS. Assessments were performed pre-surgery, at 15 and 40 min, 1 and 3 days, and 3 months after surgery. RESULTS: Tonsillectomy patients were younger [25.0 standard deviation (SD) 17.8 vs. 32.1 SD 18.0 years, P = 0.031] and had shorter anaesthesia duration (29.5 SD 12.6 vs. 42.7 SD 15.8 min, P < 0.01). Tonsillectomy patients had worse recovery in the nociceptive (pain and nausea; P < 0.001), activities of daily living (P < 0.001) and overall recovery (P = 0.025) domains, but were not different in the cognitive, emotive (depression and anxiety) or physiological recovery domains. Complete satisfaction was lower for tonsillectomy (P < 0.001). At 3 months, there was equivalence between groups in all assessments. CONCLUSION: The study shows the ability of the PQRS to discriminate recovery in different domains. Tonsillectomy has a worse recovery profile over the first 3 days in nociceptive, activities of daily living and overall recovery, which is associated with poorer satisfaction than nasal surgery.
Assuntos
Período de Recuperação da Anestesia , Cavidade Nasal/cirurgia , Tonsilectomia/métodos , Atividades Cotidianas , Adolescente , Adulto , Anestesia Geral , Criança , Cognição , Estudos de Coortes , Análise Discriminante , Feminino , Humanos , Masculino , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Náusea e Vômito Pós-Operatórios/epidemiologia , Período Pós-Operatório , Estudos Prospectivos , Tonsilectomia/psicologia , Resultado do TratamentoRESUMO
Controlling Salmonella populations on commercial broiler grow out farms is a crucial step in reducing Salmonella contamination in processing plants. Broiler litter harbors many species of pathogenic bacteria including Salmonella. Sodium bisulfate has been shown to reduce concentration of bacteria in broiler litter. In experiments 1 and 2, sodium bisulfate was applied to broiler litter at rates that are comparable to what is commonly used by the poultry industry: 22.7, 45.4, and 68.0 kg/92.9 m(2). After application, sodium bisulfate was mixed into the litter. In experiments 3 and 4, sodium bisulfate was applied at 45.4 kg/92.9 m(2) to the surface of the litter. For all experiments, a cocktail of 5 Salmonella serovars was applied to the litter. Ammonia, pH, moisture, and water activity measurements were taken; additionally, total aerobic, anaerobic, enteric, and Salmonella concentrations were determined at 0, 24, and 96 h. In experiments 1 and 2, Salmonella concentrations were higher for treated litter than the control at 24 and 96 h (P < 0.001). In experiments 1 and 2, litter pH was lower for treated litter at 24 and 96 h; lowest pH was observed with the 68.0 kg/92.9 m(2), with a pH of 5.95 (P < 0.001). In experiments 3 and 4, litter pH was lowered for treated litter to 2.1 (P < 0.001). Even this lower pH did not reduce Salmonella concentrations compared with the control (P = 0.05). The decreased litter pH appeared to be responsible for increased viability of Salmonella. This research shows that the lowering of litter pH, which decreases litter ammonia production, could actually lead to an increased survivability of certain bacteria, such as Salmonella.
Assuntos
Galinhas , Pisos e Cobertura de Pisos/normas , Abrigo para Animais/normas , Viabilidade Microbiana/efeitos dos fármacos , Salmonella/efeitos dos fármacos , Sulfatos/farmacologia , Animais , Desinfetantes/administração & dosagem , Desinfetantes/farmacologia , Concentração de Íons de Hidrogênio , Sulfatos/administração & dosagem , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: There is a well-known relationship between MS and damage to the optic nerve, but advanced, quantitative MR imaging methods have not been applied to large cohorts. Our objective was to determine whether a short imaging protocol (< 10 minutes), implemented with standard hardware, could detect abnormal water diffusion in the optic nerves of patients with MS. MATERIALS AND METHODS: We examined water diffusion in human optic nerves via DTI in the largest MS cohort reported to date (104 individuals, including 38 optic nerves previously affected by optic neuritis). We also assessed whether such abnormalities are associated with loss of visual acuity (both high and low contrast) and damage to the retinal nerve fiber layer (assessed via optical coherence tomography). RESULTS: The most abnormal diffusion was found in the optic nerves of patients with SPMS, especially in optic nerves previously affected by optic neuritis (19% drop in FA). DTI abnormalities correlated with both retinal nerve fiber layer thinning (correlation coefficient, 0.41) and loss of visual acuity, particularly at high contrast and in nerves previously affected by optic neuritis (correlation coefficient, 0.54). However, diffusion abnormalities were overall less pronounced than retinal nerve fiber layer thinning. CONCLUSIONS: DTI is sensitive to optic nerve damage in patients with MS, but a short imaging sequence added to standard clinical protocols may not be the most reliable indicator of optic nerve damage.
Assuntos
Imagem de Tensor de Difusão/métodos , Esclerose Múltipla/patologia , Nervo Óptico/patologia , Neurite Óptica/patologia , Retina/patologia , Transtornos da Visão/patologia , Adulto , Idoso , Estudos de Coortes , Imagem de Tensor de Difusão/normas , Imagem de Tensor de Difusão/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Nervo Óptico/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Acuidade Visual , Água/metabolismo , Adulto JovemRESUMO
We investigated the influence of either propofol or desflurane on the incidence of postoperative cognitive dysfunction in a randomised trial of 180 patients undergoing coronary artery bypass surgery. The primary outcome was incidence of postoperative cognitive dysfunction at 3 months, defined as ≥1 SD deterioration in two or more of 12 neurocognitive tests. Secondary outcomes included early postoperative cognitive dysfunction (between days three and seven), delirium on day one, morbidity and length of hospital stay. Early postoperative cognitive dysfunction was significantly higher with propofol compared with desflurane (56/84 (67.5%) vs 41/83 (49.4%), respectively, p=0.018), but this effect was not seen at 3 months (10/87 (11.2%) vs 9/90 (10.0%), respectively. There was no difference in delirium (7/89 (7.9%) vs 12/91 (13.2%), respectively, length of hospital stay (median (IQR [range]) 7 (6-9 [4-15]) vs 6 (5-7 [5-16) days, respectively or other morbidities. Desflurane was associated with reduced early cognitive dysfunction.
Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Transtornos Cognitivos/etiologia , Ponte de Artéria Coronária/efeitos adversos , Isoflurano/análogos & derivados , Propofol/farmacologia , Idoso , Cognição/efeitos dos fármacos , Desflurano , Feminino , Seguimentos , Humanos , Isoflurano/farmacologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de RiscoRESUMO
OBJECTIVES: To provide information on the susceptibility of Staphylococcus aureus causing skin and soft tissue infections (SSTIs) in France, Ireland and the UK. PATIENTS AND METHODS: One thousand three hundred and ninety patients attending their general practitioners for skin infections were recruited. Susceptibility to 11 antimicrobials using CLSI (formerly NCCLS) broth microdilution was determined for 646 S. aureus isolates detected in the evaluable patient population. RESULTS: Susceptibility results were similar in the UK and Ireland, but differed in France. The largest difference between countries was observed for erythromycin and fusidic acid. In France, 67.8% of isolates were susceptible to erythromycin when compared with 88.6% in Ireland and 92.8% in the UK. However, 93.7% of French isolates were susceptible to fusidic acid, compared with 68.6% in Ireland and 75.6% in the UK. A diagnosis of impetigo was associated with reduced fusidic acid susceptibility. CONCLUSIONS: Differences in the prevalence of certain diagnoses, particularly impetigo, rather than differences in antibiotic consumption may explain some of the observed differences in susceptibility seen between these countries.
Assuntos
Anti-Infecciosos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Serviços de Saúde Comunitária/métodos , Farmacorresistência Bacteriana/fisiologia , França/epidemiologia , Humanos , Irlanda/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma. OBJECTIVES: This pilot study examined the effect of roflumilast on allergen-induced airway hyperresponsiveness (AHR) to histamine challenge and asthmatic response to allergen challenge. METHODS: In a randomized, double-blind, 2-period, crossover trial, 13 patients with mild allergic asthma [mean forced expiratory volume in 1 s (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000 microg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV(1) Assuntos
Alérgenos/efeitos adversos
, Aminopiridinas/uso terapêutico
, Benzamidas/uso terapêutico
, Hiper-Reatividade Brônquica/tratamento farmacológico
, Inibidores de Fosfodiesterase/uso terapêutico
, Administração Oral
, Adolescente
, Adulto
, Aminopiridinas/administração & dosagem
, Benzamidas/administração & dosagem
, Hiper-Reatividade Brônquica/induzido quimicamente
, Hiper-Reatividade Brônquica/fisiopatologia
, Testes de Provocação Brônquica/efeitos adversos
, Estudos Cross-Over
, Ciclopropanos/administração & dosagem
, Ciclopropanos/uso terapêutico
, Relação Dose-Resposta a Droga
, Método Duplo-Cego
, Seguimentos
, Volume Expiratório Forçado/efeitos dos fármacos
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Inibidores de Fosfodiesterase/administração & dosagem
, Projetos Piloto
, Resultado do Tratamento
RESUMO
BACKGROUND: The calcipotriol/betamethasone dipropionate two-compound product is safe and effective in the short-term treatment of psoriasis. OBJECTIVE: The primary objective was to investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks. The efficacy results are presented here. METHODS: Six hundred and thirty-four patients were randomised double-blind to treatment (once daily, when required) with either: 52 weeks of two-compound product (two-compound group), 52 weeks of alternating 4-week periods of two-compound product and calcipotriol (alternating group), or 4 weeks of two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). RESULTS: There was a trend towards a difference between treatments from the overall treatment effect for the percentage of satisfactory responses for each patient during the study (p = 0.071). This appeared to be due to the comparison of the two-compound and calcipotriol groups (p = 0.025). CONCLUSION: There was a trend towards the efficacy of the two-compound product used for up to 52 weeks being better than that of 4 weeks of the two-compound product followed by 48 weeks of calcipotriol.
Assuntos
Anti-Inflamatórios/uso terapêutico , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Betametasona/administração & dosagem , Betametasona/uso terapêutico , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Segurança , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus-host interactions is also not clear. OBJECTIVE: We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF). METHODS: Patients aged 4-12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months. RESULTS: Fifty children with acute asthma (mean age+/-SD, 7.4+/-2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4+/-16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER. CONCLUSION: RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections.
Assuntos
Asma/imunologia , Infecções por Picornaviridae/imunologia , RNA Viral/análise , Rhinovirus/imunologia , Doença Aguda , Alérgenos/imunologia , Asma/tratamento farmacológico , Asma/fisiopatologia , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Pico do Fluxo Expiratório , Infecções por Picornaviridae/fisiopatologia , RNA Viral/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Rhinovirus/isolamento & purificação , Índice de Gravidade de Doença , Testes Cutâneos , Resultado do TratamentoRESUMO
BACKGROUND: Asthma is a process of chronic allergic inflammation that may be worsened by the activation of neutrophils during acute exacerbations. OBJECTIVE: We investigated our hypothesis that changes in cellular activation may be detectable in peripheral blood (PB) during late-phase asthma and during clinical exacerbations. METHODS: Twenty-one stable asthmatics (9 on treatment with beta2-agonists only, 12 using inhaled corticosteroids) and 10 nonasthmatic volunteers were first compared using flow cytometry to measure beta2-integrin (CD11b/CD18) expression. Production of reactive oxygen species (ROS) was evaluated employing chemiluminescence. Next, 8 mild asthmatics were assessed using similar methods before and after allergen-induced late asthmatic reactions (LARs). Finally, 4 asthmatic subjects were evaluated over 3 months, and symptoms, peak expiratory flow (PEF) and ROS production were measured. Episodes of respiratory morbidity (exacerbations) were identified and their association with ROS production was examined. RESULTS: No differences were detected in adhesion molecule expression and ROS production comparing the normal and asthmatic groups. However, after development of the LAR, significant reductions in CD11b neutrophil expression (mean fluorescence intensity; MFI) were observed [before: 994 +/- 102 MFI (mean +/- SEM) versus after: 424 +/- 81 MFI; p < 0.01]. Furthermore, strong associations were found between decreases in CD11b and the severity of the LAR (r = 0.9; p < 0.02). In the clinical study, ROS production was significantly lower during exacerbations (median 43%; p < 0.05). Again, this measurement was significantly associated with reductions in PEF (r = 0.5, p < 0.03). CONCLUSIONS: In patients with mild stable asthma, no differences in the activation of circulating neutrophils were detectable compared to nonasthmatic individuals. During episodes of asthmatic airway obstruction, in the laboratory and in clinical disease, neutrophil activation decreased in PB, conceivably because activated cells may be preferentially sequestered in the lung.