RESUMEN
Involving users through participation in healthcare service and environment design is growing. Existing approaches and toolkits for practitioners and researchers are often paper based involving workshops and other more traditional design approaches such as paper prototyping. The advent of digital technology provides the opportunity to explore new platforms for user participation. This paper presents results from three studies that used a bespoke situated user participation digital kiosk, engaging 33 users in investigating healthcare environment design. The studies, from primary and secondary care settings, allowed participant feedback on each environment and proved a novel, engaging "21st century" way to participate in the appraisal of the design process. The results point toward this as an exciting and growing area of research in developing not just a new method of user participation but also the technology that supports it. Limitations were noted in terms of data validity and engagement with the device. To guide the development of user participation using similar situated digital devices, key lessons and reflections are presented.
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Participación de la Comunidad , Recolección de Datos/métodos , Planificación Ambiental , Ambiente de Instituciones de Salud , Adulto , Actitud del Personal de Salud , Terminales de Computador , Arquitectura y Construcción de Instituciones de Salud , Femenino , Humanos , Masculino , Persona de Mediana Edad , Participación del Paciente , Interfaz Usuario-Computador , Adulto JovenRESUMEN
Peyronie's disease is an inflammatory disorder, which causes thickening of the tunica albuginea of the penis. Peyronie's disease has a variable natural history and the assessment and management of the disease has yet to be standardised. The case notes of 97 patients with a diagnosis of Peyronie's disease were retrospectively reviewed at a single tertiary referral centre. Patients who were able to achieve sexual penetrative activity to the satisfaction of both partners were managed conservatively. Patients who were unable to achieve penetrative sexual activity were given intra-cavernosal prostaglandin, with those achieving a satisfactory erection being offered appropriate surgical intervention. The mean age at presentation was 50 years (range 18-82). A total of 59 (61%) men were able to have penetrative sex at the time of presentation. Following initial conservative management, only five (8%) of this group had disease progression, which stopped them from being able to penetrate. In all 38 (39%) men who were not able to penetrate at presentation were offered surgical intervention. In all 24 (63%) of these men chose to have surgical intervention. Tunical plication resulted in the ability to penetrate in 77% of men choosing this option whereas only 46% of men undergoing autologous saphenous vein grafting were able to have penetrative sex. Assessment of penetrative sexual function is an essential component of the management of patients with Peyronie's disease. This enables appropriate counselling with respect to possible conservative management or the most appropriate surgical intervention. The majority of patients with Peyronie's disease can achieve sexual penetrative activity, many without surgical intervention.
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Coito/fisiología , Induración Peniana/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Humanos , Masculino , Persona de Mediana Edad , Induración Peniana/terapia , Estudios Retrospectivos , Adulto JovenRESUMEN
The aim of this study was to assess whether environmental enrichment and environmental conditions can influence the expression of sickness behaviour. The behaviour in response to injection of lipopolysaccharide or saline was examined in a total of 96 62-weeks old hatchmate hens kept in a free range or cage environment. There were eight experimental treatments, each with 12 birds. Half the birds were sourced from a commercial cage layer unit (C/-) and half from a commercial free range unit (FR/-). After intraperitoneal injection with either lipopolysaccharide or saline (as a control), the hens were placed in either a cage (-/C) or free range (-/FR) environment. Lipopolysaccharide caused greater suppression of activity in free range (FR/FR) than in caged hens, including less walking (53% reduction), roosting (-86%) and preening (-60%) (p<0.05). Those responses were not observed in caged birds released into free range, nor in free range birds introduced to cages, suggesting that both the presence of and the familiarity with an environment affected sickness behaviour patterns. Increased sleeping was the most consistent response (+147%; p<0.001), and it was least influenced by environment. It was concluded that free range layer hens can express a greater range of sickness behaviours than caged hens, and this may make it more difficult to recognise disease expression in the caged environment.
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Bienestar del Animal , Conducta Animal/efectos de los fármacos , Pollos , Vivienda para Animales , Lipopolisacáridos/efectos adversos , Animales , FemeninoRESUMEN
INTRODUCTION: Males presenting for assisted reproduction after vasectomy have a high chance of normal spermatogenesis and of successful surgical sperm retrieval. We aimed to evaluate simple percutaneous methods of retrieving sperm for intracytoplasmic sperm injection in males with secondary azoospermia due to previous vasectomy. PATIENTS AND METHODS: We analyzed a series of post-vasectomy males who presented for sperm retrieval between 1999 and 2005 and who were not being considered for vasal reconstruction as their primary method of re-establishing their fertility. RESULTS: All 132 men had sperm retrieved successfully, 97% with percutaneous methods. In seventy-five percent of the couples intracytoplasmic sperm injection was done, with a total number of 184 cycles being performed. The clinical pregnancy and live birth rates were 25 and 24%, respectively. There were no significant scrotal haematomas, and only 2 patients had postoperative pain after percutaneous sperm retrieval that required analgesia for more than 2 days. CONCLUSION: We have shown that percutaneous sperm retrieval, where normal spermatogenesis is assumed, is successful in all men following vasectomy. Percutaneous methods of retrieving epididymal or testicular sperm are inexpensive, simple and could replace open techniques in men who are not considering vasal reconstruction following vasectomy.
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Azoospermia/terapia , Inyecciones de Esperma Intracitoplasmáticas , Recuperación de la Esperma , Espermatogénesis , Vasectomía , Adulto , Azoospermia/etiología , Azoospermia/fisiopatología , Femenino , Humanos , Nacimiento Vivo , Masculino , Persona de Mediana Edad , Embarazo , Índice de Embarazo , Recuperación de la Esperma/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION: The impact of Modernising Medical Careers on the differential need for consultant urologists and urological surgeons is as yet unknown. This study's aim was to determine what changes there had been in operative urological activity so as to predict the need for urological surgeons in the future. MATERIALS AND METHODS: A retrospective study of all elective operative urological surgery over a 15-year period was performed. The absolute numbers of patients presenting for different grades of surgery were aggregated and analysed using the Spearman's rank correlation test. RESULTS: Aggregated data from 27,839 procedures demonstrated no change in the number of operations (r 0.01; NS) or the number of diagnostic endoscopic procedures (r 0.21; NS) carried out over the study period. There was a decrease in endoscopic surgery related to a 70% reduction in trans-urethral resection of the prostate (TURP) (r -0.89; P = <0.0001) and an increase in ureteroscopic interventions (r 0.82; P = 0.0002) for stone disease. There was no change in the amount of major surgery carried out (r -0.43; NS) over the 15 years. CONCLUSIONS: There have been changes to the pattern of surgery urologists have provided over the last 15 years but the need for complex surgical interventions has not altered. This suggests there will be as great a need for operating surgeons in the future, as currently exists.
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Procedimientos Quirúrgicos Electivos/tendencias , Procedimientos Quirúrgicos Urológicos/tendencias , Movilidad Laboral , Cistoscopía/métodos , Cistoscopía/tendencias , Inglaterra , Humanos , Masculino , Estudios Retrospectivos , Resección Transuretral de la Próstata/tendencias , Enfermedades Urológicas/diagnóstico , Enfermedades Urológicas/cirugía , Vasectomía/tendenciasRESUMEN
OBJECTIVE: British Association of Urological Surgeons (BAUS) guidelines and government initiatives have put pressure on the effective use of outpatient resources. Follow up appointments need to be carefully managed to ensure efficient use of available resources. The aim of this study was to audit outpatient follow up service with particular attention to the appropriateness of the appointments made. METHODS: All patients attending a general urology clinic were assessed by a form completed for each individual appointment. The source of the appointment and the time interval was recorded and each follow up appointment was judged to be either appropriate or inappropriate by the person giving the consultation. For those deemed to be inappropriate, justification was sought and the notes independently reviewed by a different clinician to verify this categorisation. RESULTS: Of 164 appointments made, 143 patients attended for follow up. A total of 131 appointments were considered to be appropriate (92%) with only 12 deemed by the consulting clinician to be inappropriate (8%). The commonest cause for an inappropriate appointment was failure to appreciate that follow up had already been arranged for a different date. There was no correlation between the source of the referral and an inappropriate referral. CONCLUSION: This audit suggests an effective use of the outpatient follow up resource with respect to the appropriateness and timing of follow up consultations. Other areas of resource management such as default rates should be investigated in an attempt to improve the efficiency of a service.
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Atención Ambulatoria/estadística & datos numéricos , Citas y Horarios , Recursos en Salud/estadística & datos numéricos , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Inglaterra , Humanos , Auditoría Médica , Derivación y ConsultaRESUMEN
INTRODUCTION: Modernisation of Medical Careers dictates a shortening of the training required to achieve consultant status. Precisely what type of work these consultants could be expected to accomplish, and be trained to do, is not clear. The objective of this study was to demonstrate a method of stratifying urological workload so as to determine what a urological trainee, undergoing shortened training, might be expected to do as a consultant and to use this stratification to help manpower planning within the specialty. PATIENTS AND METHODS: A cohort study of all urological activity undertaken over a 3-year period in a single teaching hospital in the UK was performed. All out-patient, in-patient or day-case activity within the urological department was analysed in the years 2000-2002. Urological activity was stratified according to the absolute numbers of patients presenting for different types of out-patient consultation, the grade of complexity of any surgical intervention undertaken, and the theatre resource consumed by the study population. RESULTS: Utilising prospectively collected data, it was possible to aggregate information about the contributions generalist and sub-specialty activity made to the overall workload of a urological unit. Whilst the majority of out-patient activity, and almost 88% of the surgical workload, could be accomplished by consultants undergoing shortened training, 11.9% of specialised urological activity, consuming nearly 43% of the available theatre resource, was outwith the remit of such a specialist. CONCLUSIONS: Shortened training seems able to satisfy the service delivery needs of the majority of out-patient and day-case urological activity. It will not, however, fulfil the need for subspecialty-based training required to cope with the large minority of patients necessitating complex surgical intervention. Specialist training programmes, promoting advanced operative skills, need to be evolved in parallel to shortened training so as to ensure global urological service provision for the future.
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Atención a la Salud/normas , Educación de Postgrado en Medicina/organización & administración , Urología/educación , Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Movilidad Laboral , Estudios de Cohortes , Consultores , Inglaterra , Humanos , Estudios Prospectivos , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Factores de Tiempo , Carga de TrabajoRESUMEN
OBJECTIVE: To determine the validity of a system for coding the reason for urological referral from primary care, using ICD10, and thus enable benchmarking of urological outpatient activity. PATIENTS AND METHODS: Four studies were conducted: (i) A pilot study to aggregate information into a few input diagnosis codes (925 patients); (ii) Validation of the aggregated codes using input diagnoses from a second centre (928 patients); (iii) A prospective study by three urologists to determine the system's generic utility (918 patients); (iv) A study to aggregate the presumptive codes for 2771 patients to gain an insight into the case-mix of patients referred to a general urological service via the outpatient department. RESULTS: The aggregation of input diagnoses from general practice referrals into 36 'presumptive codes' was possible and could be validated. Prospective coding, for 96% of eligible patients, was possible with < 1% of referral diagnoses not being codable. Further aggregation of the data for 2771 patients showed that 31% were referred with urological malignancy whilst 69% had symptoms suggesting benign urological disease. CONCLUSIONS: This preliminary study of presumptive coding suggests that it is a feasible and valid method of recording the input diagnoses for patients presented to a urological service. The information it provides has relevance for the structuring, benchmarking, resourcing and manpower requirements of that service, essential components for clinical governance. It also has relevance to the prospective collection of patient data for research and audit.
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Registros Médicos/normas , Derivación y Consulta , Enfermedades Urológicas/terapia , Inglaterra , Medicina Familiar y Comunitaria , Control de Formularios y Registros , Humanos , Proyectos Piloto , Estudios Prospectivos , Estudios RetrospectivosAsunto(s)
Coristoma/diagnóstico , Enfermedades de la Vejiga Urinaria/diagnóstico , Vejiga Urinaria/patología , Adulto , Coristoma/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Conductos Paramesonéfricos/patología , Dolor Pélvico/etiología , Enfermedades de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To assess the accuracy of pre-operative diagnosis of preputial pathology ainongst urologists and general surgeons. PATIENTS AND METHODS: Data were collected on 460 adult patients having had circumcision performed by either a general surgeon or a urologist over a 10-year period. RESULTS: Pre-operative diagnosis was consistent with final histology in 83% of cases and further management was never altered by the histological result. Re-referral rates were 0% for general surgeons and 2.7% for urologists (P > 0.05) and there were no cases needing further surgical intervention. CONCLUSIONS: Routine submission of histological specimens for analysis and out-patient follow-up are not required following circumcision.
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Circuncisión Masculina , Fimosis/etiología , Adolescente , Adulto , Anciano , Estudios de Seguimiento , Humanos , Masculino , Fimosis/patología , Cuidados Preoperatorios/métodos , Derivación y Consulta/estadística & datos numéricos , Estudios Retrospectivos , Sensibilidad y EspecificidadAsunto(s)
Quistes/congénito , Enfermedades de los Genitales Masculinos/congénito , Vesículas Seminales , Adulto , Quistes/cirugía , Enfermedades de los Genitales Masculinos/cirugía , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Dolor/prevención & control , Tomografía Computarizada por Rayos X , Ultrasonografía IntervencionalRESUMEN
A major function of p27, also known as Kip1, is to bind and inhibit cyclin/cyclin-dependent kinase complexes, thereby blocking cell cycle progression. As p27 operates at the heart of the cell cycle, it is perhaps not surprising that it is emerging as a key player in multiple cell fate decisions including proliferation, differentiation, and cell death. The central role of p27 makes it important in a variety of disease processes that involve aberrations in cellular proliferation and other cell fates. Most notable among these processes is neoplasia. A large number of studies have reported that p27 expression is frequently downregulated in human tumors. In most tumor types, reduced p27 expression correlates with poor prognosis, making p27 a novel and powerful prognostic marker. In addition to these practical implications, murine and tissue culture models have shown that p27 is a potent tumor suppressor gene for multiple epithelially derived neoplasias. Loss of p27 cooperates with mutations in several oncogenes and tumor suppressor genes to facilitate tumor growth, indicating that p27 may be a "nodal point" for tumor suppression. In contrast to most tumor suppressor genes studied to date, which are recessive at the cellular level, p27 is haploinsufficient for tumor suppression. The fact that tumor suppression by p27 is critically dependent on the absolute level of p27 expression indicates that p27 acts as a rheostat rather than as an on/off switch to control growth and neoplasia.
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Genes Supresores de Tumor , Proteínas Asociadas a Microtúbulos/fisiología , Neoplasias/genética , Proteínas Supresoras de Tumor , Animales , Apoptosis , Adhesión Celular , Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Femenino , Sustancias de Crecimiento/fisiología , Humanos , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Neoplasias/metabolismo , Proteínas Oncogénicas/metabolismo , Proteínas Oncogénicas Virales/metabolismoRESUMEN
A significant minority of patients will require specialist advice or further treatment after undergoing a TURP. Nurse-led telephone follow-up provides such patients with easy continued access to a specialist centre. When setting up a post-surgical telephone follow-up clinic, issues relating to patient selection, staff availability and administrative support needs must be considered.
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Alta del Paciente , Cuidados Posoperatorios/enfermería , Teléfono , Resección Transuretral de la Próstata/enfermería , Estudios de Seguimiento , Humanos , Masculino , Satisfacción del Paciente , Evaluación de Programas y Proyectos de SaludRESUMEN
Germline mutations in BRCA1 predispose to breast and ovarian cancer. Most germline BRCA1 mutations are small insertions, deletions, or single base pair (bp) substitutions. These mutation classes are rarely found as somatic mutations in BRCA1. On the other hand, somatic deletions of multiple mega-base pairs (Mb) including BRCA1, as reflected by loss of heterozygosity, occur frequently in both inherited and sporadic breast and ovarian cancers. To determine whether deletions or rearrangements of hundreds to thousands of bps might contribute to inherited mutation in BRCA1, we developed a Long PCR strategy for screening the entire genomic BRCA1 locus in high-risk families. We evaluated genomic DNA from one high-risk family of European ancestry with BRCA1-linked cancer in which no genomic mutations had been detected using conventional methods. Long PCR revealed a complex mutation, g.12977 ins10 del1039 (based on GenBank L78833), comprising an inverted duplication and deletion in BRCA1 that removes portions of exon 3 and intron 3, including the 5' splice site for intron 3. As a result of the deletion, exon 3 is skipped, leading to a truncated protein and disease predisposition. Unlike previously reported large germline deletions in BRCA1, neither breakpoint resides within an Alu element. The g.12977 ins10 del1039 mutation was not detected among 11 other breast cancer families, nor among 406 breast cancer patients unselected for family history.
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Proteína BRCA1/genética , Neoplasias de la Mama/genética , Reordenamiento Génico , Mutación de Línea Germinal/genética , Neoplasias Ováricas/genética , Elementos Alu/genética , Deleción Cromosómica , Exones/genética , Femenino , Amplificación de Genes , Humanos , Intrones/genética , Pérdida de Heterocigocidad/genética , Masculino , LinajeRESUMEN
OBJECTIVE: To critically evaluate the infection rate associated with the use of a nonrefluxing irrigation system for outpatient flexible cystoscopy, by comparing it with conventional irrigation systems, and to determine the costs and benefits of this system of irrigation delivery. PATIENTS AND METHODS: All patients undergoing flexible cystoscopy on scheduled outpatient lists were considered for inclusion in the study; 143 patients of 220 undergoing cystoscopy fulfilled the study criteria. The study group of patients underwent cystoscopy with a new single-use nonrefluxing valve inserted into the same irrigation delivery system that was used for the whole endoscopy session, and the control group had the complete irrigation system changed after each endoscopic examination. Midstream urine samples were taken for analysis before cystoscopy and again 3-4 days later. Infection was defined as a pure growth of >/= 105 organisms/mL, with associated pyuria defined as >/= 10 pus cells per high power microscopic field. RESULTS: Complete data were available on 133 patients, with a further nine being excluded from the statistical analysis because they had a pre-existing urinary tract infection, leaving 64 patients in the study and 69 in the control groups. The overall infection rate for flexible cystoscopy was 3.2%, with no significant difference between the study and control groups. Cost savings of > 35% can be expected using the nonrefluxing valve method of irrigation delivery. CONCLUSION: The nonrefluxing valve caused no detectable increase in patient morbidity from bacterial infection when compared with conventional irrigation systems for flexible cystoscopy, and can save considerable costs.
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Cistoscopía/métodos , Piuria/etiología , Irrigación Terapéutica/instrumentación , Anciano , Atención Ambulatoria/economía , Análisis Costo-Beneficio , Cistoscopios/efectos adversos , Cistoscopios/economía , Cistoscopía/efectos adversos , Cistoscopía/economía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Piuria/orina , Irrigación Terapéutica/efectos adversos , Irrigación Terapéutica/economíaRESUMEN
Scrotal ultrasound scanning is now a routine and mandatory investigation of the patient presenting with scrotal symptoms. The need for scrotal ultrasound scanning when the physical examination reveals no significant abnormality has not been previously assessed. We conducted a retrospective study of 160 patients attending for scrotal ultrasound over a period of 1 year. The accuracy of clinical examination was compared with the gold standard of ultrasound for identifying clinically significant lesions. The sensitivity, specificity and positive and negative predictive values were calculated. Four clinically relevant groups were used for analysis purposes: Group I, acutely painful scrotum with or without swelling; Group II, chronic testicular pain without swelling; Group III, chronic scrotal swelling with or without pain; and Group IV, the asymptomatic testis. In Group I, sensitivity was 100%, specificity was 81.3%, the positive predictive value was 92.1% and the negative predictive value was 100%. In Group II, sensitivity was 71.4%, specificity was 90.9%, the positive predictive value was 76.9% and the negative predictive value was 88.2%. In Group III, sensitivity was 88.9%, specificity was 66.7%, the positive predictive value was 92.3% and the negative predictive value was 57.1%. In Group IV, sensitivity was 33.3%, specificity was 100%, the positive predictive value was 100% and the negative predictive value was 93.9%. All clinically significant abnormalities were identified on clinical examination. Clinically insignificant lesions identified by ultrasound alone did not affect the clinical management. It is recommended that scrotal ultrasound is used in the acutely painful scrotum where a confident diagnosis cannot be made or there is failure to respond to treatment, and in the chronic swelling where a confident clinical diagnosis cannot be made.
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Enfermedades de los Genitales Masculinos/diagnóstico por imagen , Escroto/diagnóstico por imagen , Enfermedad Aguda , Adolescente , Adulto , Anciano , Enfermedad Crónica , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
Diclofenac (a non-steroidal anti-inflammatory drug) and pethidine (a synthetic opiate) are the two analgesics most commonly used to relieve the pain of ureteric colic. Fast frame renography is a non-invasive means of imaging ureteric peristalsis and renal drainage. The aim of this study was to determine the effects of each of these drugs on the drainage pattern of the upper tracts. Twelve normal male volunteers were studied. All underwent a standard fast frame renogram using 75 MBq of technetium-99m-mercaptoacetyltriglycine, and were then administered either 100 mg pethidine or 75 mg diclofenac by intramuscular injection. Fast frame renography was then repeated. Peristalsis was determined from the condensed image of each ureter and the renogram curves were analysed to obtain standard parameters and deconvolution analysis. Diclofenac caused a profound disruption to both ureteric peristalsis and the renogram curve. This effect was not seen after the administration of pethidine. Deconvolution analysis suggests the effects of diclofenac are mediated via a direct effect on drainage rather than by any alteration of blood flow to the kidney. This study suggests that pethidine is the analgesic of choice prior to renography and that inferences about alterations of drainage in the presence of diclofenac should be interpreted with care.
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Analgésicos Opioides/farmacología , Antiinflamatorios no Esteroideos/farmacología , Diclofenaco/farmacología , Meperidina/farmacología , Uréter/efectos de los fármacos , Uréter/diagnóstico por imagen , Adulto , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Radiografía , Renografía por Radioisótopo , Valores de ReferenciaRESUMEN
This study investigated drip loss in chilled beef (hot-boned m. longissimus lumborum (LL)) under conventional packaging systems, in which a vacuum is applied, and non-vacuum packaging systems. The use of vacuum during the packaging process (vacuum packaging, CO(2) atmosphere packaging) was associated with increased drip. Drip was lower in heat-shrunk vacuum packaging than in non-shrunk vacuum packaging. A slow vacuum onset had no effect on drip formation, or may have increased it. The extent of pressure reduction (vacuum; range 0-1 atm) did not significantly affect drip formation, although the standard vacuum pressure (0 atm) tended to cause more drip loss than higher pressures. The three non-vacuum anaerobic packaging systems tested were: flushed with carbon dioxide without the pressure being reduced below atmospheric (Flush), or the same system with no CO(2) flush but a proprietary oxygen absorber added (Scavenger), or a combination of both (Flush/Scavenger). Storage was at -1.5 °C for up to 20 weeks. The Flush and Flush/Scavenger systems had considerably lower drip loss than the CAP standard system (6.4%, 6.5%, and 9.1% respectively); the Scavenger system had the lowest drip loss (5.2%). Drip losses generally increased with storage period, irrespective of packaging system. All non-vacuum packaging systems except the Flush system had very low oxygen levels (<0.l% v v ). The Flush system had considerably higher levels of oxygen (0.9%) with associated browning of meat samples. All packaging systems gave a hygienic shelf-life of at least 16 weeks. At 16 weeks, microbial numbers were highest (5 × 10(6)) in the Scavenger system. The meat from all packaging systems was acceptable to taste panels even after 16 weeks of storage at -1.5 °C. There were no significant differences between any of the packaging systems for any of the sensory attributes tested. The packaging systems with the best all round performance were the Flush/Scavenger and the Scavenger systems, depending on the storage-life required.