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BACKGROUND: The study assessed whether a "7-1-7" timeliness metric for screening and TB preventive therapy (TPT) could be implemented for household contacts (HHCs) of index patients with bacteriologically confirmed pulmonary TB under routine programmatic settings in Kenya. METHODS: A longitudinal cohort study conducted among index patients and their HHCs in 12 health facilities, Kiambu County, Kenya. RESULTS: Between January and June 2023, 95% of 508 index patients had their HHCs line-listed within 7 days of initiating anti-TB treatment ("First 7"). In 68% of 1,115 HHCs, screening outcomes were ascertained within 1 day of line-listing ("Next 1"). In 65% of 1,105 HHCs eligible for further evaluation, anti-TB treatment, TPT or a decision for no drugs was made within 7 days of screening ("Second 7"). Altogether, 62% of screened HHCs started TPT during the "7-1-7" period compared with 58% in a historical cohort. Main barriers to TPT uptake were HHCs not consulting clinicians, HHCs being unwilling to initiate TPT and drug shortages. Healthcare workers felt that a timeliness metric was valuable for streamlining HHC management and proposed "3-5-7" as a workable alternative. CONCLUSIONS: The national TB programme must generate awareness about TPT, ensure uninterrupted drug supplies and assess whether the "3-5-7" metric can be operationalised.
CONTEXTE: L'étude a évalué si une mesure de rapidité "7-1-7" pour le dépistage et le traitement préventif de la TB (TPT) pouvait être mise en Åuvre pour les contacts familiaux des patients index atteints de TB pulmonaire confirmée bactériologiquement dans le cadre d'un programme de routine au Kenya. MÉTHODES: Étude de cohorte longitudinale menée auprès de patients index et de leurs contacts familiaux dans 12 établissements de santé du comté de Kiambu, au Kenya. RÉSULTATS: Entre janvier et juin 2023, 95% des 508 patients index ont eu leur centre de santé inscrit sur la liste dans les 7 jours suivant le début du traitement antituberculeux (« First 7 ¼ ). Dans 68% des 1 115 centres de santé, les résultats du dépistage ont été vérifiés dans le jour suivant l'inscription sur la liste (« Next 1 ¼). Dans 65% des 1 105 centres de santé éligibles pour une évaluation plus approfondie, le traitement antituberculeux, le TPT ou la décision de ne pas prendre de médicaments a été prise dans les 7 jours suivant le dépistage (« Second 7 ¼). Au total, 62% des patients dépistés ont commencé un traitement antituberculeux au cours de la période « 7-1-7 ¼, contre 58% dans une cohorte historique. Les principaux obstacles à l'adoption du TPT étaient les suivants : les centres de santé ne consultaient pas les cliniciens, les centres de santé n'étaient pas disposés à commencer le TPT et les pénuries de médicaments. Les professionnels de la santé ont estimé qu'une mesure de la rapidité d'exécution était utile pour rationaliser la gestion des centres de santé et ont proposé le « 3-5-7 ¼ comme solution de rechange viable. CONCLUSION: Le programme national de lutte contre la TB doit sensibiliser au TPT, garantir un approvisionnement ininterrompu en médicaments et évaluer si la mesure « 3-5-7 ¼ peut être mise en Åuvre.
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Trazado de Contacto , Tuberculosis Pulmonar , Humanos , Sector Privado , India/epidemiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Tamizaje Masivo/métodosRESUMEN
BACKGROUND AND PURPOSE: The pathogenesis of febrile status epilepticus is poorly understood, but prior studies have suggested an association with temporal lobe abnormalities, including hippocampal malrotation. We used a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. MATERIALS AND METHODS: Brain MR imaging was performed in children presenting with febrile status epilepticus and control subjects as part of the Consequences of Prolonged Febrile Seizures in Childhood study. Medial temporal lobe morphologic parameters were measured manually, including the distance of the hippocampus from the midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. RESULTS: Temporal lobe morphologic parameters were correlated with the presence of visual hippocampal malrotation; the strongest association was with left temporal horn width (P < .001; adjusted OR, 10.59). Multiple morphologic parameters correlated with febrile status epilepticus, encompassing both the right and left sides. This association was statistically strongest in the right temporal lobe, whereas hippocampal malrotation was almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persisted when the analysis was restricted to cases with visually normal imaging findings without hippocampal malrotation or other visually apparent abnormalities. CONCLUSIONS: Several component morphologic features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum.
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Convulsiones Febriles/etiología , Estado Epiléptico/etiología , Lóbulo Temporal/anomalías , Niño , Preescolar , Estudios de Cohortes , Femenino , Hipocampo/anomalías , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Neuroimagen , Lóbulo Temporal/diagnóstico por imagenRESUMEN
OBJECTIVE: To assess trends in the nutritional quality of hospital menus and examine differences between menus used in hospitals with cook-chill or cook-fresh food services. DESIGN: Standard patient menus were analysed against 28 criteria to assess nutritional standards and compared with results from similar studies in 1986 and 1993. SETTING: Menus were collected from 80 hospitals in New South Wales (NSW), Australia, including 36 using cook-chill food service systems. STATISTICAL ANALYSIS: Chi-squared analysis was used to assess differences between the proportions of hospitals meeting the criteria in 1993 and 2001, and between different types of hospitals. RESULTS: In 2001, compared with 1993, significantly many hospitals offered more than one hot choice at the evening meal, more menus highlighted low fat items and more calcium-rich foods were available. More than 90% of hospitals allowed patients to select their own menu, offered wholemeal breads and high-fibre breakfast cereals, fresh fruit, polyunsaturated margarine, a milk dessert at least once a day and two or more hot options at the midday meal. Hospitals with cook-chill food services had menus that were more likely to meet nutritional recommendations, although they were less likely to offer a choice of serving size. A high proportion of unpopular choices were offered in menus, especially meat dishes and desserts. APPLICATIONS/CONCLUSION: Since 1986, NSW hospital menus have improved to offer choices that conform better to dietary guidelines. Cook-chill food services may have positive and negative impacts on meal choices. The assessment criteria are useful in hospitals to assess their menus.
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Manipulación de Alimentos/métodos , Servicio de Alimentación en Hospital/estadística & datos numéricos , Servicio de Alimentación en Hospital/normas , Planificación de Menú/normas , Planificación de Menú/tendencias , Fenómenos Fisiológicos de la Nutrición/fisiología , Australia , Distribución de Chi-Cuadrado , Culinaria , Grasas de la Dieta/administración & dosificación , Preferencias Alimentarias/fisiología , Humanos , Refrigeración , Cloruro de Sodio Dietético/administración & dosificaciónAsunto(s)
Coagulasa/metabolismo , Genes Bacterianos/genética , Infecciones Estafilocócicas/genética , Staphylococcus/genética , Humanos , Unidades de Cuidados Intensivos , Resistencia a la Meticilina/genética , Reacción en Cadena de la Polimerasa , Staphylococcus/enzimología , Staphylococcus aureus/genéticaRESUMEN
Research indicates that computerized decision support systems (CDSSs) can improve clinical performance and patient outcomes, and yet CDSSs are not in widespread use. Physician guidelines, in general, face barriers in implementation. Guidelines in a computerized format can overcome some of the barriers to conventional text-form guidelines; however, computerized programs have novel aspects that have to be considered, aspects such as technical problems/support and user interface issues that can act as barriers. Though the literature points out that human, organizational, and technical issues can act as barriers in the implementation of CDSSs, studies clearly indicate that there are methods that can overcome these barriers and improve CDSS acceptance and use. These methods come from lessons learned from a variety of CDSS implementation ventures. Notably, most of the methods that improve acceptance and use of a CDSS require feedback and involvement of end-users. Measuring and addressing physician or user attitudes toward the computerized support system has been shown to be important in the successful implementation of a CDSS. This article discusses: 1) the barriers of implementation of guidelines in general and of CDSSs; 2) the importance of the physician's role in development, implementation, and adherence; 3) methods that can improve CDSS acceptance and use; and 4) the types of tools needed to obtain end-user feedback.
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Sistemas de Apoyo a Decisiones Clínicas , Difusión de Innovaciones , Guías de Práctica Clínica como Asunto , Programas Informáticos , Actitud del Personal de Salud , Toma de Decisiones en la Organización , Retroalimentación , Implementación de Plan de Salud , Humanos , Médicos/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Ropivacaine provides effective spinal anaesthesia for total hip arthroplasty. This study was designed to compare the efficacy and safety of plain ropivacaine with plain bupivacaine for spinal anaesthesia in patients undergoing total hip arthroplasty. METHODS: Sixty-six patients, ASA I or II, were randomized to receive an intrathecal injection of one of two local anaesthetic solutions. Group R (n=32) received 3.5 ml of ropivacaine 5 mg ml(-1) (17.5 mg). Group B (n=34) received 3.5 ml of bupivacaine 5 mg ml(-1) (17.5 mg). The onset and duration of sensory block at dermatome level T10, maximum upper and lower spread of sensory block and the onset, intensity and duration of motor block were recorded, as were safety data. RESULTS: Onset of motor and sensory block was rapid with no significant differences between the two groups. The median time of onset of sensory block at the T10 dermatome was 2 min (range 2-5 min) in Group R and 2 min in Group B (range 2-9 min). The median duration of sensory block at the T10 dermatome was 3.0 h (range 1.5-4.6 h) in Group R and 3.5 h (2.7-5.2 h) in Group B (P<0.0001). The median duration of complete motor block (modified Bromage Scale 3) was significantly shorter in the ropivacaine group compared with the bupivacaine group (2.1 vs 3.9 h, P<0.001). CONCLUSIONS: Intrathecal administration of either 17.5 mg plain ropivacaine or 17.5 mg plain bupivacaine was well tolerated and an adequate block for total hip arthroplasty was achieved in all patients. A more rapid postoperative recovery of sensory and motor function was seen in Group R compared with Group B.
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Amidas/administración & dosificación , Anestesia Raquidea/métodos , Anestésicos Locales/administración & dosificación , Artroplastia de Reemplazo de Cadera , Bupivacaína/administración & dosificación , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Inyecciones Espinales , Masculino , Persona de Mediana Edad , Bloqueo Nervioso , Satisfacción del Paciente , Ropivacaína , Factores de TiempoRESUMEN
OBJECTIVE: To determine whether there was a clinically significant effect on troponin T measurement when the sample was collected in a heparinized (plasma) blood collection tube compared with a serum tube. METHODS: Prospective cohort study using a convenience sample of 198 patients with undifferentiated illness presenting to an Emergency Department who required troponin T measurement. Samples were collected in both plain (serum) tubes and plasma tubes for comparison. All samples were measured using an Elecsys 2010 Immunoassay system (Roche-Boehringer Mannheim, Germany). RESULTS: There were 35 troponin T measurements > or = 0.03 microg/L (the limit of reproducibility of the test). The negative predictive value for troponin T performed in heparinized tubes compared with plain tubes was 100% (95% confidence interval 96.4-100) at the > or = 0.03 microg/L level and 100% (95% confidence interval 97-100%) at the > or = 0.1 microg/L level. At a cut-off point for risk stratification in acute coronary syndromes (> or = 0.1 microg/L), there was 100% concordance between the two measurements for each sample. CONCLUSION: The use of plasma (heparinized) tubes for the collection of troponin T samples is unlikely to produce clinically significant false-negative results compared with collection of troponin T samples in serum (plain) tubes.
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Recolección de Muestras de Sangre/instrumentación , Recolección de Muestras de Sangre/normas , Heparina/sangre , Troponina T/sangre , Técnicas de Diagnóstico Cardiovascular/normas , Reacciones Falso Negativas , Humanos , Técnicas In Vitro , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
This study was designed to evaluate the efficacy and safety of two concentrations of intrathecal ropivacaine, 7.5 and 10 mg ml(-1), in patients undergoing total hip arthroplasty. One hundred and four patients, ASA I-III, were randomized to receive an intrathecal injection of one of two concentrations of isobaric ropivacaine. Group 1 (n=51) received 2.5 ml of 7.5 mg ml(-1) ropivacaine (18.75 mg). Group 2 (n=53) received 2.5 ml of 10 mg ml(-1) ropivacaine (25 mg). The onset and offset of sensory block at dermatome level T10, maximum upper and lower spread of sensory block and the onset, intensity and duration of motor block were recorded, as were safety data. Onset of motor and sensory block was rapid with no significant differences between the two groups. The median time of onset of sensory block at the T10 dermatome was 2 min (range 1-25 min) in Group 1 and 2 min (range 1-21 min) in Group 2. The median duration of sensory block at the T10 dermatome was 3.0 h (range 0.5-4.2 h) in Group 1 and 3.4 h (1.1-5.9 h) in Group 2 (P=0.002). The median duration of complete motor block was significantly prolonged (P<0.05) in Group 2 compared with Group 1 (1.9 vs 1.2 h, respectively). Anaesthetic conditions were excellent in all but one patient. Intrathecal ropivacaine, in doses of 18.75 and 25 mg, was well tolerated and provided effective anaesthesia for total hip arthroplasty.
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Amidas/administración & dosificación , Anestesia Raquidea/métodos , Anestésicos Locales/administración & dosificación , Artroplastia de Reemplazo de Cadera , Adulto , Anciano , Anciano de 80 o más Años , Amidas/farmacología , Anestésicos Locales/farmacología , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Movimiento/efectos de los fármacos , Soluciones Farmacéuticas , Ropivacaína , Sensación/efectos de los fármacos , Gravedad Específica , Factores de TiempoRESUMEN
Pre-clinical studies in mice and haemophilic dogs have shown that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX (FIX) into skeletal muscle results in sustained expression of F.IX at levels sufficient to correct the haemophilic phenotype. On the basis of these data and additional pre-clinical studies demonstrating an absence of vector-related toxicity, we initiated a clinical study of intramuscular injection of an AAV vector expressing human F.IX in adults with severe haemophilia B. The study has a dose-escalation design, and all patients have now been enrolled in the initial dose cohort (2 x 10(11) vg/kg). Assessment in the first three patients of safety and gene transfer and expression show no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against F.IX. We found that the vector sequences are present in muscle by PCR and Southern-blot analyses of muscle biopsies and we demonstrated expression of F.IX by immunohistochemistry. We observed modest changes in clinical endpoints including circulating levels of F.IX and frequency of FIX protein infusion. The evidence of gene expression at low doses of vector suggests that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offers the possibility of converting severe haemophilia B to a milder form of the disease.
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Dependovirus/genética , Factor IX/genética , Terapia Genética , Vectores Genéticos/uso terapéutico , Hemofilia B/terapia , Músculo Esquelético/metabolismo , Adulto , Anciano , Pruebas de Coagulación Sanguínea , Southern Blotting , Factor IX/análisis , Expresión Génica , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Hemofilia B/genética , Humanos , Inyecciones Intramusculares , Masculino , Músculo Esquelético/virología , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes de Fusión/análisis , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Resultado del TratamientoRESUMEN
This paper aimed to determine the criteria participants use to make decisions about scarce medical resources (allocation to use a kidney machine). It varied information about patients on 4 factors (sex, smoking, employment status, community service). It also set out to see if decisions made in groups differed from aggregated decisions of those made alone. In the first study, participants completed a simple questionnaire requiring them to rank-order sixteen hypothetical patients. In the second study, a group discussion (in groups of three participants) preceded the group putting an agreed rating on the identical questionnaire. Participants favoured patients who were employed, non-smokers and participated in community service. This suggests that participants adopted a utilitarian moral ideology. Participants' smoking habits interacted with the hypothetical patients' smoking habits, indicating in-group favouritism. In the second study it was found that when the decision was made in a group of three it amplifies the decision made by an individual. In this sense there was clear evidence of group polarization.
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Conducta de Elección , Selección de Paciente , Asignación de Recursos , Deseabilidad Social , Investigación Empírica , Empleo , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Opinión Pública , Diálisis Renal/ética , Asignación de Recursos/ética , Factores Sexuales , FumarRESUMEN
Recombinant adeno-associated virus (AAV)-based vectors capable of expressing therapeutic gene products in vivo have shown significant promise for human gene therapy. A major challenge for these applications is the development of processes to enable production of large quantities of AAV vectors and purification of material that is well characterized and appropriate for parenteral administration. Several cell culture systems have been developed for AAV vector production, and a limited number of these demonstrate the potential to generate AAV vectors at concentrations compatible with cost-effective large-scale production. Vector purification protocols, in particular those based on the use of scalable column chromatography, have concurrently been developed that demonstrate the potential to provide highly purified AAV vector preparations with high yield. These advances support the potential for AAV vectors as therapeutic agents for gene therapy.
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One factor limiting the ability to modify human repopulating hematopoietic cells genetically with retroviral vectors is the relatively low expression of the cognate viral receptor. We have tested sequential transduction of human hematopoietic cells with an adenoviral vector encoding the ecotropic retroviral receptor followed by transduction with an ecotropic retroviral vector. Adenoviral transduction of K562 erythroleukemia cells was highly efficiently with >95% of cells expressing the ecotropic receptor at a multiplicity of infection (MOI) of 103with a correspondingly high transduction with a retroviral vector. Ecotropic receptor expression in CD34+ cells following transduction with adenoviral vectors was increased by at least two-fold (from 20 to 48%) by replacing the RSV promoter with the CMV E1a promoter, resulting in a parallel increase in retroviral transduction efficiency. Replacing the head portion of the fiber protein in conventional adenoviral vectors (serotype 5) with the corresponding portion from an adenoviral 3 serotype resulted in ecotropic receptor expression in 60% of CD34+ cells at an MOI of 104 and a retroviral transduction of 60% of hematopoietic clonogenic progenitors. The sequential transduction strategy also resulted in efficient transduction of the primitive CD34+CD38- subset suggesting that it may hold promise for genetic modification of human hematopoietic stem cells.
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Adenoviridae/genética , Vectores Genéticos/genética , Células Madre Hematopoyéticas/fisiología , Glicoproteínas de Membrana/genética , Receptores Virales/genética , Transducción Genética/genética , Animales , Antígenos CD34/metabolismo , Células Cultivadas , Humanos , Ratones , Proteínas Recombinantes de Fusión/farmacologíaAsunto(s)
Arterias Carótidas/fisiopatología , Músculo Liso Vascular/fisiopatología , Inhibidor Tisular de Metaloproteinasa-1/fisiología , Túnica Íntima/fisiopatología , Adenoviridae , Animales , Arterias Carótidas/patología , Traumatismos de las Arterias Carótidas , Cateterismo/efectos adversos , Técnicas de Transferencia de Gen , Vectores Genéticos , Músculo Liso Vascular/lesiones , Músculo Liso Vascular/patología , Ratas , Inhibidor Tisular de Metaloproteinasa-1/genética , Túnica Íntima/lesiones , Túnica Íntima/patologíaRESUMEN
BACKGROUND: Cell migration is a major contributor to injury-induced neointimal hyperplasia and depends on alteration of the proteolytic balance within the arterial wall toward matrix breakdown. This is partly mediated by the matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). METHODS AND RESULTS: An increase in expression of biologically active and immunoreactive TIMP-1 was seen in vitro after infection of rat smooth muscle cells (SMCs) with Av1.TIMP1 (an adenoviral vector containing the human TIMP1 cDNA). Infection of rat SMCs with Av1.TIMP1 reduced migration in vitro by 27% compared with control virus-infected cells (37.6+/-4.34 versus 51+/-5.01 cells per high-power field, P<0.05). The adenoviral vector was delivered to the injured rat carotid artery, and 4 days later, immunoreactive protein was identified and migration of SMCs reduced by 60% (5.2+/-0. 5 versus 12.8+/-1.5 cells per section, P<0.05, n=5). Neointimal area 14 days after injury showed a 30% reduction in the animals receiving the Av1.TIMP1 virus compared with controls (0.09+/-0.01 versus 0. 14+/-0.01 mm2, P=0.02, n=14). CONCLUSIONS: The response to arterial balloon injury involves MMP-dependent SMC migration and can be attenuated in vivo by the transmural expression of TIMP-1 by adenoviral gene transfer.
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Adenoviridae/genética , Angioplastia de Balón/efectos adversos , Vectores Genéticos , Músculo Liso Vascular/química , Músculo Liso Vascular/citología , Inhibidor Tisular de Metaloproteinasa-1/genética , Animales , Membrana Basal/química , Membrana Basal/citología , Membrana Basal/metabolismo , División Celular/fisiología , Movimiento Celular/fisiología , Células Cultivadas , ADN/biosíntesis , ADN Complementario , Modelos Animales de Enfermedad , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Regulación Viral de la Expresión Génica , Humanos , Hiperplasia , Masculino , Músculo Liso Vascular/virología , Ratas , Ratas Wistar , Túnica Íntima/química , Túnica Íntima/patologíaRESUMEN
BACKGROUND: A recent clinical trial of an antineuroblastoma vaccine used adenovirus serotype 5 (Ad5) vectors to transduce autologous tumor cells with the gene encoding IL-2. A method to improve transduction efficiency was sought to enable the use of lower viral titers, especially when in situ adenoviral-mediated tumor cell transduction is considered. MATERIALS AND METHODS: A chimeric adenoviral delivery vector was utilized in which the fiber head from adenovirus serotype 3 was incorporated into the backbone of Ad5. Since the fiber head protein is responsible for viral attachment to target cells, a different spectrum and range of infectivity might result. Both the chimeric (Av9LacZ4) and Ad5 (Av1LacZ4) vectors were constructed to carry a beta-galactosidase transgene. The relative transduction efficiency of these two vectors was then evaluated in five tumor-derived short-term neuroblastoma cultures and four established neuroblastoma cell lines. Enzyme activity was assessed using three different methods: in situ staining, flow cytometric analysis, and a quantitative assay. RESULTS: A significant improvement in transduction efficiency of the short-term neuroblastoma cultures with the new chimeric adenovector was demonstrated. A similar improvement in transduction efficiency was not observed in the established cell lines, suggesting that the cell surface receptor for the Ad 3 serotype had been lost in vitro. Increased transduction of tumor cells with N-myc amplification was also observed. CONCLUSIONS: The newly constructed chimeric adenoviral vector transduces short-term neuroblastoma cultures more efficiently than the standard Ad5 vector. This vector will permit the use of lower viral titers and may be useful in other adenoviral-based gene-therapy protocols. Increased transgene expression in N-myc-amplified cells offers possible selectivity for in situ gene delivery.