RESUMO
Socio-economic deprivation is associated with adverse maternal and childhood outcomes. Epidural analgesia, the gold standard for labour analgesia, may improve maternal well-being. We assessed the association of socio-economic status with utilisation of epidural analgesia and whether this differed when epidural analgesia was advisable for maternal safety. This was a population-based study of NHS data for all women in labour in Scotland between 1 January 2007 and 23 October 2020, excluding elective caesarean sections. Socio-economic status deciles were defined using the Scottish Index of Multiple Deprivation. Medical conditions for which epidural analgesia is advisable for maternal safety (medical indications) and contraindications were defined according to national guidelines. Of 593,230 patients in labour, 131,521 (22.2%) received epidural analgesia. Those from the most deprived areas were 16% less likely to receive epidural analgesia than the most affluent (relative risk 0.84 [95%CI 0.82-0.85]), with the inter-decile mean change in receiving epidural analgesia estimated at -2% ([95%CI -2.2% to -1.7%]). Among the 21,219 deliveries with a documented medical indication for epidural analgesia, the socio-economic gradient persisted (relative risk 0.79 [95%CI 0.75-0.84], inter-decile mean change in receiving epidural analgesia -2.5% [95%CI -3.1% to -2.0%]). Women in the most deprived areas with a medical indication for epidural analgesia were still less likely (absolute risk 0.23 [95%CI 0.22-0.24]) to receive epidural analgesia than women from the most advantaged decile without a medical indication (absolute risk 0.25 [95%CI 0.24-0.25]). Socio-economic deprivation is associated with lower utilisation of epidural analgesia, even when epidural analgesia is advisable for maternal safety. Ensuring equitable access to an intervention that alleviates pain and potentially reduces adverse outcomes is crucial.
Assuntos
Analgesia Epidural , Analgesia Obstétrica , Dor do Parto , Trabalho de Parto , Gravidez , Humanos , Feminino , Criança , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Analgésicos , Dor do Parto/tratamento farmacológico , Escócia , Fatores SocioeconômicosRESUMO
Lumbar epidural is the gold standard for labour analgesia. Low concentrations of local anaesthetic are recommended. This network meta-analysis investigated whether further reducing the concentration of local anaesthetic can improve maternal and neonatal outcomes without compromising analgesia. We conducted a systematic search of relevant databases for randomised controlled trials comparing high (>0.1%), low (>0.08% to ≤0.1%) or ultra-low (≤0.08%) concentration local anaesthetic (bupivacaine or equivalent) for labour epidural. Outcomes included mode of delivery, duration of labour and maternal/neonatal outcomes. Bayesian network meta-analysis with random-effects modelling was used to calculate odds ratios or weighted mean differences and 95% credible intervals. A total of 32 studies met inclusion criteria (3665 women). The total dose of local anaesthetic received increased as the concentration increased; ultra-low compared with low (weighted mean difference -14.96 mg, 95% credible interval [-28.38 to -1.00]) and low compared with high groups (weighted mean difference -14.99 [-28.79 to -2.04]), though there was no difference in the number of rescue top-ups administered between the groups. Compared with high concentration, ultra-low concentration local anaesthetic was associated with increased likelihood of spontaneous vaginal delivery (OR 1.46 [1.18 to 1.86]), reduced motor block (Bromage score >0; OR 0.32 [0.18 to 0.54]) and reduced duration of second stage of labour (weighted mean difference -13.02 min [-21.54 to -4.77]). Compared with low, ultra-low concentration local anaesthetic had similar estimates for duration of second stage of labour (weighted mean difference -1.92 min [-14.35 to 10.20]); spontaneous vaginal delivery (OR 1.07 [0.75 to 1.56]; assisted vaginal delivery (OR 1.35 [0.75 to 2.26]); caesarean section (OR 0.76 [0.49 to 1.22]); pain (scale 1-100, weighted mean difference -5.44 [-16.75 to 5.93]); and maternal satisfaction. Although a lower risk of an Apgar score < 7 at 1 min (OR 0.43 [0.15 to 0.79]) was reported for ultra-low compared with low concentration, this was not sustained at 5 min (OR 0.12 [0.00 to 2.10]). Ultra-low concentration local anaesthetic for labour epidural achieves similar or better maternal and neonatal outcomes as low and high concentration, but with reduced local anaesthetic consumption.
Assuntos
Analgesia Epidural , Analgesia Obstétrica , Anestésicos Locais , Analgésicos , Teorema de Bayes , Cesárea , Feminino , Humanos , Recém-Nascido , Metanálise em Rede , GravidezRESUMO
Centralization of care has improved outcomes in esophagogastric (EG) cancer surgery. However, specialist surgical centers often work within clinical silos, with little transfer of knowledge and experience. Although variation exists in multiple dimensions of perioperative care, the differences in operative technique are rarely studied. An esophageal anastomosis workshop was held to identify areas of common and differing practice within the operative technique. Surgeons showed videos of their anastomosis technique by open and minimally invasive surgery. Each video was followed by a discussion. Surgeons from 10 different EG cancer centers attended. Eight key technical differences and learning points were identified and discussed: the optimum diameter of the gastric conduit; avoiding ischemia in the gastric conduit; minimizing esophageal trauma; the use of an esophageal mucosal collar; omental wrapping; intraoperative leak testing; ideal diameter of the circular stapler and the growing use of linear stapled anastomoses. The workshop received positive feedback from participants and on 2 years follow-up, 40% stated that they believed that the learning of tips and techniques during the workshop has contributed to lowering their anastomotic leak rate. Many differences exist in surgical technique. The reasons for, and crucially the significance of, these differences must be discussed and examined. Workshops provide a forum for peer-to-peer collaborative learning to reflect on one's own practice and improve surgical technique. These changes can, in turn, generate incremental improvements in patient care and postoperative outcomes.
Assuntos
Neoplasias Esofágicas , Práticas Interdisciplinares , Anastomose Cirúrgica , Fístula Anastomótica/etiologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Grampeamento CirúrgicoRESUMO
Gestational breast cancer (GBC) presents many challenges for women and the clinicians who care for them. The aim of this study was to explore the health care experiences of women diagnosed with GBC to inform and improve clinical care of women in this predicament. Semi-structured interviews were conducted with 17 women who had been diagnosed with GBC in the previous 5 years. The overarching themes for perceived quality of care were "communication" and "comprehensive care." "Communication" had two sub themes: "interdisciplinary communication" (the way health professionals from different disciplines communicated with each other about the management of the woman's care) and "patient communication" (how they communicated this to the woman). The "comprehensive care" theme incorporated three sub themes: "the spirit" (psychological care); "the mind" (information provision); and "the body" (management of treatment side effects). Women's own accounts of positive and negative experiences of GBC care provide unique and specific insights which improve understanding of their concerns and needs. The findings can inform advances in quality and efficacy of clinical care; offer guidance for obstetricians, oncologists and allied health professionals about the needs of women diagnosed with GBC and how care can be optimised; and inform the development of resources to assist women and their families.
Assuntos
Neoplasias da Mama/terapia , Prestação Integrada de Cuidados de Saúde/normas , Qualidade da Assistência à Saúde/normas , Adulto , Comunicação , Feminino , Humanos , Comunicação Interdisciplinar , Pessoa de Meia-Idade , Gravidez , Relações Profissional-Paciente , Pesquisa QualitativaRESUMO
The objective of this systematic review is to identify key components of enhanced recovery protocols (ERP) that lead to improved length of hospital stay (LOS) following esophagectomy. Relevant electronic databases were searched for studies comparing clinical outcome from esophagectomy followed by a conventional pathway versus ERP. Relevant outcome measures were compared and metaregression was performed to identify the key ERP components associated with reduced in LOS. Thirteen publications were included, ERP was associated with no changes in in-hospital mortality, total complications, anastomotic leak, or pulmonary complications compared with a conventional pathway, however LOS was reduced in the ERP group. Metaregression identified that immediate extubation was associated with reduced LOS (OR = -0.51, 95%CI -0.77 to -0.25; P < 0.01). Several postoperative factors were associated with a significant reduction in length of hospital stay, and in order of most important were (i) gastrograffin swallow ≤5 days (OR = -4.27, 95%CI -4.50 to -4.03); (ii) mobilization on postoperative day ≤1 (OR = -2.49, 95%CI -2.63 to -2.34); (iii) removal of urinary catheter ≤2 days (OR = -0.99, 95%CI -1.15 to -0.84); (iv) oral intake with at least sips of fluid ≤1 day (OR = -0.96, 95%CI -1.24 to -0.68); (v) enteral diet with feeding jejunostomy or gastrostomy ≤ 1 day (OR = -0.57, 95%CI -0.80 to -0.35) and (vi) epidural removal ≤ 4 days (OR = -0.17, 95%CI -0.27 to -0.07). Several core ERP components and principles appear to be associated with LOS reduction. These elements should form a part of the core ERP for the specialty, while surgical teams incorporate other elements through an iterative process.
Assuntos
Esofagectomia , Tempo de Internação , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/etiologia , Extubação , Analgesia Epidural , Meios de Contraste/administração & dosagem , Diatrizoato de Meglumina/administração & dosagem , Ingestão de Líquidos , Deambulação Precoce , Nutrição Enteral , Esofagectomia/efeitos adversos , Mortalidade Hospitalar , Humanos , Fatores de Tempo , Cateterismo UrinárioRESUMO
Specific reading disability (SRD) is now widely recognised as often being caused by phonological processing problems, affecting analysis of spoken as well as written language. According to one theoretical account, these phonological problems are due to low-level problems in auditory perception of dynamic acoustic cues. Evidence for this has come from studies showing poor discrimination of frequency-modulated from unmodulated tones. We measured frequency modulation detection limens (FMDLs) in 16 children with specific reading disability (SRD group), 16 children with mild to moderate hearing loss (SNH group) and 16 age-matched controls (CA group) aged 8-14. To obtain information about possible mechanisms used in frequency modulation detection, FMDLs were measured at modulation rates of 2 and 20 Hz, both in the absence and the presence of amplitude modulation, intended to force listeners to rely, if possible, upon phase-locking cues. Although both the SNH and SRD groups showed a trend for elevated FMDLs at both 2 and 20 Hz, these differences reached statistical significance for the SNH group alone. However, the SNH group had no evidence of literacy impairments. This study thus shows that impairments in perceiving dynamically modulated auditory stimuli do not necessarily lead to difficulty in learning to read.
Assuntos
Dislexia/fisiopatologia , Perda Auditiva Neurossensorial/fisiopatologia , Percepção da Altura Sonora/fisiologia , Acústica da Fala , Distúrbios da Fala/etiologia , Adolescente , Análise de Variância , Audiometria de Tons Puros , Limiar Auditivo , Estudos de Casos e Controles , Criança , Dislexia/complicações , Feminino , Perda Auditiva Neurossensorial/complicações , Humanos , Masculino , Mascaramento Perceptivo/fisiologia , Psicometria , Análise de Regressão , Distúrbios da Fala/fisiopatologiaRESUMO
It has been suggested that specific reading disability (SRD) may be attributable to an impaired ability to perceive spectral differences between sounds that leads to a deficit in frequency discrimination and subsequent problems with language and literacy. The objective of the present study was three-fold. We aimed to (a) determine whether children with mild to moderate sensorineural hearing loss were impaired in their ability to discriminate frequency, (b) assess the extent to which any such deficits may be due to an inability to use information derived from phase locking, and (c) examine whether frequency discrimination abilities were predictive of measures of word and nonword reading and nonword repetition. Difference limens for frequency (DLFs) were obtained for 22 children with mild to moderate hearing loss (SNH group) and 22 age-matched controls (CA group) at central frequencies of 1 kHz, where phase-locking information is available, and 6 kHz, where it is not. A battery of standardized tests of language and literacy was also administered. The SNH group exhibited significantly elevated DLFs at both 1 and 6 kHz relative to controls, despite considerable variability of thresholds in both groups. Although no group differences were found for receptive and expressive vocabulary, receptive grammar, and nonword reading, the SNH group performed worse than controls on word reading and nonword repetition, even though word reading scores were age-appropriate. Frequency discrimination abilities were associated with reading and nonword repetition across groups, but these correlations largely disappeared when the two groups were analyzed separately. Together, these results provide evidence for a dissociation between impaired frequency discrimination and relatively "spared" language and literacy in children with mild to moderate sensorineural hearing loss. These results cast doubt on the assertion that a deficit in frequency discrimination necessarily leads to marked deficits in the development of language and literacy.
Assuntos
Linguagem Infantil , Dislexia/etiologia , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/fisiopatologia , Transtornos do Desenvolvimento da Linguagem/etiologia , Discriminação da Altura Tonal/fisiologia , Adolescente , Análise de Variância , Audiometria de Tons Puros , Limiar Auditivo/fisiologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Testes de Linguagem , Masculino , Psicometria , Acústica da FalaRESUMO
The interaction between indomethacin and probenecid has been studied in 17 patients with rheumatoid arthritis with the use of a specific gas-liquid chromatographic method for the assay of indomethacin in plasma and urine. Probenecid in a dose of 0.5 gm twice daily improved the therapeutic response to indomethacin administered in a dose of 25 mg 3 times daily for a 3-wk period. There was an increase in the mean AUC of indomethacin in plasma from 2,553 +/- 213 hr ng/ml to 4,181 +/- 384 hr ng/ml when probenecid was given, but there was no change in the plasma half-life of indomethacin. There was a reduction in the mean plasma clearance of indomethacin from 174 +/- 21 ml/kg/hr to 107 +/- 14 ml/kg/hr when probenecid was added to the indomethacin therapy and a decrease in the apparent volume of distribution from 0,927 +/- 0.16 L/kg to 0.613 +/- 0.13 L/kg. There was no change in the amount of free indomethacin excreted in the urine during probenecid therapy but there was a reduction in the urinary excretion of free plus glucuronide conjugate of indomethacin from 8,967 +/- 867 microgram/day to 4,760 +/- 674 microgram/day, with a fall in the mean renal clearance of indomethacin glucuronide from 271 +/- 48 ml/min to 126 +/- 57.0 ml/min. The changes in the plasma indomethacin concentration profile during probenecid therapy are due to a decrease in the nonrenal clearance of indomethacin possibly because of reduced biliary clearance.
Assuntos
Indometacina/metabolismo , Probenecid/metabolismo , Adulto , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Proteínas Sanguíneas/metabolismo , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Indometacina/uso terapêutico , Cinética , Masculino , Pessoa de Meia-Idade , Probenecid/uso terapêutico , Ligação ProteicaRESUMO
A sudden increase in the incidence of milk off-flavours in bulk tank milk from Prince Edward Island (Canada) dairy farms in the late 1990s prompted an investigation of potential herd-level risk factors. A prospective case-control study was conducted from 2000 to 2002. Data on herd management were obtained by questionnaire and field investigation from all the 62 identified off-flavour positive farms (cases) and 62 loosely matched (for data-collection convenience) off-flavour negative farms (controls). Forty-three of the 62 cases (69%) of milk off-flavours identified during the study period were classified as "transmitted" (feed) off-flavours, and 9 (15%), 6 (10%), and 4 (6%) as "rancid", "oxidized" and "malty" off-flavours, respectively. Given this evidence and the relatively low incidence of other flavour defects in milk, only transmitted-flavour cases were considered in the analyses of risk factors. Poor air quality in the lactating cows' barn (OR = 40.8), using baled silage as the main forage (OR = 10.6), as well as feeding roughage before milking (OR = 253.3) or as a free choice (OR = 3.2) all were significantly (P < 0.05) associated with the incidence of transmitted flavours in bulk-tank milk. Clipping the hair on the cows' udder (OR = 0.07) and changing the bedding material more than once a day (OR = 0.12) were protective. The finding about feeding baled silage before milking has raised hypotheses about silage composition (in particular the off-flavour compounds or their precursors) and also about the process of silage making itself.
Assuntos
Mastite Bovina/epidemiologia , Leite/fisiologia , Ração Animal , Animais , Estudos de Casos e Controles , Bovinos , Indústria de Laticínios , Feminino , Incidência , Mastite Bovina/etiologia , Mastite Bovina/prevenção & controle , Odorantes , Ilha do Príncipe Eduardo/epidemiologia , Estudos Prospectivos , Fatores de Risco , Estações do Ano , Silagem , Inquéritos e Questionários , PaladarRESUMO
Although the use of Freund's Complete Adjuvant (FCA) has been discouraged for the production of polyclonal antibodies, little clinical evidence supports the belief that FCA necessarily affects the well-being of immunized rabbits. We designed the present study to determine whether immunization at multiple sites with small volumes of Freund's adjuvant affects rabbit well-being. We injected 18 female New Zealand White rabbits (six animals per group) with antigen in FCA, Freund's Incomplete Adjuvant, or physiologic saline in the following volumes and routes: 0.02 to 0.03 mL intradermally in each of 30 to 40 sites and 0.1 mL subcutaneously in each of two sites. The body weight, temperature, complete blood count, and behavior of the rabbits in the home cage, upon handling, and in an open field did not differ significantly among the immunization groups during the 7-week assessment period. Only the degree of induration around injection sites differed: as expected, FCA induced the greatest response at the injection sites, but the sites were neither ulcerative nor necrotic, nor did palpation of the sites induce any apparent discomfort to the rabbits. We conclude that FCA may be used safely and humanely in rabbits if small volumes are injected intradermally or subcutaneously in multiple sites.
Assuntos
Bem-Estar do Animal , Comportamento Animal/fisiologia , Adjuvante de Freund/imunologia , Imunização/veterinária , Coelhos/fisiologia , Animais , Contagem de Células Sanguíneas/veterinária , Temperatura Corporal , Peso Corporal , Feminino , Adjuvante de Freund/administração & dosagem , Adjuvante de Freund/efeitos adversos , Proteínas de Choque Térmico/administração & dosagem , Histocitoquímica , Injeções Intradérmicas/veterinária , Injeções Subcutâneas/veterinária , Rim/patologia , Fígado/patologia , Pulmão/patologia , Muramidase/administração & dosagem , Coelhos/psicologiaRESUMO
INTRODUCTION: The management of acute postoperative pain poses a significant challenge in surgical specialities. Despite the prevalence and impact of acute postoperative pain, there is a paucity of published data regarding its occurrence and sensory qualities after joint replacement. HYPOTHESIS: That a proportion of patients would experience severe acute postoperative pain at rest after total hip replacement (THR) and total knee replacement (TKR). MATERIALS AND METHODS: Pain was assessed preoperatively, and then five times daily for the first three postoperative days in 105 THR and TKR patients. Pain severity was assessed using a pain Visual Analogue Scale and the sensory qualities of pain were assessed using the pain descriptors from the Short-Form McGill Pain Questionnaire. RESULTS: Median acute pain scores peaked on the first postoperative day, with 58% of TKR patients and 47% of THR patients reporting moderate-severe pain. Preoperative pain was most frequently described as aching, stabbing and sharp, whereas acute postoperative pain was described as aching, heavy and tender. Night pain disturbed between 44-57% of TKR patients and 21-52% of THR patients on postoperative nights 1-3. DISCUSSION: These findings demonstrate that acute postoperative pain at rest after joint replacement, particularly TKR, is poorly managed, although it does not reach the severity of preoperative pain. LEVEL OF EVIDENCE: Level IV (observational cohort study).
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Dor Pós-Operatória/etiologia , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Índice de Gravidade de Doença , Sono , Inquéritos e Questionários , Fatores de TempoRESUMO
The National Influenza Surveillance Scheme includes data from sentinel general practice consultations for influenza-like illness, laboratory reports of influenza and absenteeism rates from a national employer. The 1998 season was dominated by an increase in influenza A in all States and Territories and low influenza B activity. All influenza A isolates were characterised as influenza A (H3N2). Peak activity in 1998 was recorded in July and August. Data are coordinated, analysed and disseminated at a national level and published in Communicable Diseases Intelligence during the influenza season.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Influenza Humana/epidemiologia , Vigilância da População , Distribuição por Idade , Austrália/epidemiologia , Feminino , Humanos , Incidência , Vírus da Influenza A , Vírus da Influenza B , Masculino , Nova Zelândia/epidemiologia , Estações do Ano , Distribuição por SexoRESUMO
Twenty-one patients with rheumatoid arthritis were given indomethacin 25 mg t.i.d. by mouth for 3 weeks followed by indomethacin 25 mg t.i.d. plus a 100 mg suppository at night, after a 5-day period on placebo capsules. The mean (+/- S.E.) 24-hour creatinine clearance was 57.8 +/- 5.7 ml/min in the placebo period and was not significantly altered during indomethacin therapy, 53.1 +/- 5.5 ml/min in the oral period and 56.6 +/- 6.4 ml/min in the oral plus suppository period (P greater than 0.1). In 6 volunteers, duplicate 2-hour creatinine clearances were performed after a single oral dose of 50 mg indomethacin. After placebo capsules the mean creatinine clearance was 133.7 +/- 9.5 ml/min and after 50 mg indomethacin it was 126.5 +/- 8.9 ml/min (P greater than 0.1). In 4 of the volunteers the mean creatinine clearance after 8 days on indomethacin 25 mg q.i.d. was 117.1+/- 5.3 ml/min (P greater than 0.1). Indomethacin plasma concentrations were in the usual range for the dose given. Indomethacin caused no reduction in the creatinine clearance in spite of causing significant inhibition of prostaglandin E synthesis.
Assuntos
Indometacina/efeitos adversos , Rim/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Idoso , Creatinina/sangue , Creatinina/urina , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Indometacina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Placebos , Supositórios , Fatores de TempoRESUMO
1 Indomethacin 100 mg nightly for 1 week has been administered to 13 patients with rheumatoid arthritis by both oral and rectal routes in a double-blind, randomized, cross-over study. 2 Clinical assessments were performed at 09.00 and 14.00 h on the last 3 days of each active treatment period and compared to the results on the last 2 days of the placebo control period. 3 Indomethacin produced significant improvements in the clinical assessments at both 09.00 and 14.00 h compared to placebo but not differences were seen between the two routes of administration. 4 No significant difference was seen in the side effects experienced in the two periods. 5 The mean (+/- s.e. mean) plasma indomethacin concentration at 09.00 h in the oral period was 200.3 +/- 27.4 ng/ml, not significantly different from that in the suppository period (220.0 +/- 28.9 ng/ml). 6 Indomethacin 100 mg nightly by mouth is as effective as a 100 mg suppository and easier to administer.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Indometacina/administração & dosagem , Administração Oral , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Indometacina/efeitos adversos , Indometacina/sangue , Indometacina/uso terapêutico , Masculino , Pessoa de Meia-Idade , SupositóriosRESUMO
Investigation of 44 paired test and control patients, all suffering from rheumatoid arthritis, following exposure to phenylbutazone (PBZ) and/or oxyphenbutazone (OPB), suggests that there is no significant increase in the level of chromosomal damage in lymphocytes. The control subjects comprised two series, one previously exposed to PBZ and/or OPB, but not for at least 1-5 years, and the other never exposed to PBZ or OPB. No significant difference in the level of chromosome damage was found between patients never exposed, previously exposed, or now receiving PBZ and/or OPB.
Assuntos
Cromossomos/efeitos dos fármacos , Fenilbutazona/farmacologia , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxifenilbutazona/farmacologia , Fenilbutazona/sangue , Classe Social , Fatores de TempoRESUMO
Fifteen patients with rheumatoid arthritis received indomethacin in three treatment schedules; indomethacin retard 75 mg twice daily; indomethacin capsules 50 mg three times daily; and indomethacin 100 mg suppository at night with 50 mg by mouth each morning. The study was a double-blind, double-dummy one with each treatment being given for 2 weeks after a washout period of 3 days. After the washout period, and at the end of each 2 week active treatment period, blood samples were taken during a dosage interval for assay of indomethacin concentrations in plasma. Clinical assessments were also performed. All three treatment period produced significant clinical improvements in the assessments compared with the placebo washout period. However, no differences were seen between the treatments. Side effects occurred with equal frequency in all three periods, and the anticipated reduction in central nervous system side effects during the indomethacin retard period was not seen. Plasma concentrations of indomethacin were significantly higher during indomethacin retard therapy with a peak concentration of 2500 +/- 25 ng ml-1 during indomethacin retard therapy (mean +/- s.d.) and 1900 +/- 200 ng ml during conventional oral therapy. Indomethacin retard is as effective as the other formulations of indomethacin but appears to offer no significant advantages.
Assuntos
Indometacina/administração & dosagem , Idoso , Artrite Reumatoide/tratamento farmacológico , Preparações de Ação Retardada , Feminino , Humanos , Indometacina/metabolismo , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
Twenty patients with definite or classical rheumatoid arthritis entered and completed a sequential study of placebo for 1 week, oral indomethacin 25 mg 3 times a day for 3 weeks, and oral indomethacin 25 mg 3 times a day plus 100 mg indomethacin suppository at night for 3 weeks. Twelve of the patients had previously been classified as responders and eight as nonresponders to indomethacin by an independent assessor. At the end of each period patients were assessed by a blind observer for duration of morning stiffness, pain score, digital joint size, grip strength, articular index, analgesic tablet usage, and the patient's own overall global assessment and comparative global assessment. In 8 of the 9 tests used responders improved on indomethacin in comparison with placebo, while nonresponders did not improve. There were no significant differences between responders and nonresponders in the plasma half-life, plasma clearance of indomethacin, protein binding of indomethacin, or urinary excretion of free or conjugated indomethacin. There were no significant differences between responders and nonresponders in the urinary excretion of 7HDPA or in the platelet aggregation or platelet malonyldialdehyde production tests. In responders there was a significant positive correlation between the plasma indomethacin concentration (r=0.44, P<0.05) and the percentage inhibition of malonyldialdehyde production by the platelets. However, in nonresponders this correlation, while significant (P<0.05), was negative (r=-0.498). Both for responders and nonresponders there was a significant correlation between plasma indomethacin concentration and the percentage reduction in 7HDPA. There was no correlation between the clinical response and the plasma concentration of indomethacin. There appears to be a biochemical difference between responders and nonresponders, which, while not necessarily causally linked with the clinical response to indomethacin, is worthy of further study.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Indometacina/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/urina , Plaquetas/efeitos dos fármacos , Ensaios Clínicos como Assunto , Feminino , Humanos , Indometacina/sangue , Indometacina/urina , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacosRESUMO
In 1998 there were 85,096 notifications to the National Notifiable Diseases Surveillance System; slightly lower than in 1997 (89,579). The number of measles cases remained low, and well below the number reported in the outbreak years of 1993 and 1994. Rubella notifications further decreased and remained low in 1998. The Measles Control Campaign from August to November 1998, did not impact significantly on the number of measles or rubella cases reported for 1998. Notifications of Haemophilus influenzae type b reached a record low since surveillance began in 1991, and appeared to have stabilised at a low rate since the introduction of the conjugated vaccine in 1992. The previously reported outbreak of pertussis in 1997 tapered off in early 1998. Food-borne disease, or detection of disease, appeared to be on the rise with an increase in notification rates of campylobacteriosis and salmonellosis. Notifications of hepatitis A decreased, correcting the previous high number of notifications in 1997. Sexually transmissible diseases (STDs) increased. Notifications for chlamydial infection were the highest for all sexually transmitted diseases and third highest for all notifiable diseases. Notifications of gonococcal infection also continued to rise and have doubled since 1991, whilst notifications for syphilis increased slightly after falling steadily over recent years. Arbovirus infections of concern in 1998 were dengue outbreaks in Far North Queensland and the first case of Japanese Encephalitis for mainland Australia, highlighting the importance of surveillance of arboviruses and vectors for their detection and management.