Experience with nalbuphine, a new opioid analgesic, in acute myocardial infarction.

A total of 141 patients admitted to hospital with a diagnosis of suspected myocardial infarction were randomized to treatment with intravenous diamorphine (71) or nalbuphine (70). Myocardial infarction was subsequently confirmed in 109 patients. Both drugs provided good analgesia. Heart rate, blood pressure, respiratory rate, peak flow and minute volume were measured over a three-hour study period. Except for a slight fall in systolic blood pressure in the nalbuphine-treated group, there were no statistically significant differences between the groups. The nalbuphine-treated group had higher levels of aspartate aminotransferase and hydroxybutyric acid dehydrogenase but not creatine phosphokinase. The haemodynamic outcome and mortality at three months of the two groups were similar. It is concluded that nalbuphine provides effective analgesia coupled with few adverse circulatory or respiratory effects.     

Incorporating economic analysis in evidence-based guidelines for mental health: the profile approach

BACKGROUND: Many western health systems are currently developing the role of clinical guidelines to promote effective and efficient health care. However, introducing economic data into guideline methodology designed to assess the effectiveness of interventions raises some methodological issues. These include providing valid and generalizable cost estimates, the weight placed upon cost "evidence" and presenting cost-effectiveness information in a way that is helpful to clinicians. AIM OF THE STUDY: To explore a framework for including economic concepts in the development of a series of primary care guidelines, two of which address mental health conditions. METHODS: A profile approach, setting out best available evidence about the attributes of treatment choices (effectiveness, tolerability, safety, health service delivery, quality of life, resource use and cost), was used to help clinicians to derive treatment recommendations in a manner consistent with both the clinical decision-making process and social objectives. RESULTS: Clinicians involved in guideline development responded well to the process. Although there was often considerable debate about the meaning and importance of different aspects of evidence about treatment, in none of the guideline groups was there failure to agree treatment recommendations. DISCUSSION: The profile approach may be particularly useful in the field of mental health where disease processes may often feature very disparate effects, over long periods of time and impacting upon a broad circle of relatives, carers and agencies in addition to the patients themselves. CONCLUSION: A method has been applied in a series of primary care guidelines, which appears to enable clinicians to consider the issue of resource use alongside the various clinical attributes associated with treatment decisions. The basis of this work is the belief that guidance presenting physical measures describing effectiveness, adverse events, safety, compliance and quality of life, alongside resource consequences, is most likely to appropriately inform doctor-patient interactions. IMPLICATIONS FOR HEALTH CARE PROVISON AND USE: This research may provide a useful platform for other groups considering how to introduce cost-effectiveness concepts into guideline development groups. Whether guidelines change clinical behaviour remains a research question, and the subject of forthcoming trials. IMPLICATIONS FOR HEALTH POLICY FORMULATION: It is important that government agencies realize that guideline development is a health policy tool with prescribed methods to produce valid guidelines. Attempts to tamper with the methodology for cost-containment purposes or other political reasons are likely to discredit a useful mechanism for improving the scientific basis of health care provision. IMPLICATIONS FOR FURTHER RESEARCH: There are a number of limitations to completed work: for example it has a primary care focus and addresses fairly narrowly defined conditions. Work is ongoing to extend the scope to broader disease areas and to secondary care.     

Evaluation of the FRAX and Garvan fracture risk calculators in older women

Fracture risk calculators estimate the absolute risk of osteoporotic fractures. We investigated the performance of the FRAX and Garvan Institute fracture risk calculators in healthy, older, New Zealand, postmenopausal women with normal bone mineral density (BMD) for their age. Fractures were ascertained in women initially enrolled in a 5‐year trial of calcium supplements and followed on average for 8.8 years. Baseline data (1422 women, mean age 74 years, mean femoral neck BMD T‐score –1.3) were used to estimate fracture risk during follow‐up using the FRAX and Garvan calculators. The FRAX–New Zealand tool was used both with and without baseline BMD. The discrimination of the calculators was assessed using the area under the curve (AUC) of receiver operating characteristic curves. The calibration was assessed by comparing estimated risk of fracture with fracture incidence across a range of estimated fracture risks and clinical factors. For each fracture subtype, the calculators had comparable moderate predictive discriminative ability (AUC range: hip fracture 0.67–0.70; osteoporotic fracture 0.62–0.64; any fracture 0.60–0.63) that was similar to that of models using only age and BMD. The Garvan calculator was well calibrated for osteoporotic fractures but overestimated hip fractures. FRAX with BMD underestimated osteoporotic and hip fractures. FRAX without BMD underestimated osteoporotic and overestimated hip fractures. In summary, none of the calculators provided better discrimination than models based on age and BMD, and their discriminative ability was only moderate, which may limit their clinical utility. The calibration varied, suggesting that the calculators should be validated in local cohorts before clinical use. © 2011 American Society for Bone and Mineral Research.     

Predicting Renal Function Outcomes After Partial and Radical Nephrectomy

Background

Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.

Improving influenza virus backbones by including terminal regions of MDCK-adapted strains on hemagglutinin and neuraminidase gene segments

Reverse genetics approaches can simplify and accelerate the process of vaccine manufacturing by combining the desired genome segments encoding the surface glycoproteins from influenza strains with genome segments (backbone segments) encoding internal and non-structural proteins from high-growth strains. We have developed three optimized high-growth backbones for use in producing vaccine seed viruses for group A influenza strains. Here we show that we can further enhance the productivity of our three optimized backbones by using chimeric hemagglutinin (HA) and neuraminidase (NA) genome segments containing terminal regions (non-coding regions (NCRs) and coding regions for the signal peptide (SP), transmembrane domain (TMD), and cytoplasmic tail (CT)) from two MDCK-adapted high growth strains (PR8x and Hes) and the sequences encoding the ectodomains of the A/Brisbane/10/2010 (H1N1) HA and NA proteins. Viruses in which both the HA and NA genome segments had the high-growth terminal regions produced higher HA yields than viruses that contained one WT and one chimeric HA or NA genome segment. Studies on our best-performing backbone indicated that the increases in HA yield were also reflected in an increase in HA content in partially purified preparations. Our results show that the use of chimeric HA and NA segments with high-growth backbones is a viable strategy that could improve influenza vaccine manufacturing. Possible mechanisms for the enhancement of HA yield are discussed.     

Target viewing time and velocity effects on prehension

 The goal of the present study was to understand which characteristics (movement time or velocity) of target motion are important in the control and coordination of the transport and grasp-preshape components of prehensile movements during an interception task. Subjects were required to reach toward, grasp and lift an object as it entered a target area. Targets approached along a track at four velocities (500, 750, 1000 and 1250 mm/s) which were presented in two conditions. In the distance-controlled condition, targets moving at all velocities traveled the same distance. In the viewing-time-controlled condition, combinations of velocity and starting distances were performed such that the moving target was visible for 1000 ms for all trials. Analyses of kinematic data revealed that when, target distance was controlled, velocity affected all transport-dependent measures; however, when viewing time was controlled, these dependent measures were no longer affected by target velocity. Thus, the use of velocity information was limited in the viewing-time-controlled condition, and subjects used other information, such as target movement time, when generating the transport component of the prehensile movement. For the grasp-preshape component, both peak aperture and peak-aperture velocity increased as target velocity increased, regardless of condition, indicating that target velocity was used to control the spatial aspects of aperture formation. However, the timing of peak aperture was affected by target velocity in the distance-controlled condition, but not in the viewing-time-controlled condition. These results provide evidence for the autonomous generation of the spatial and temporal aspects of grasp preshape. Thus, an independence between the transport and grasp-preshape phases was found, whereby the use of target velocity as a source of information for generating the transport component was limited; however, target velocity was an important source of information in the grasp-preshape phase. Received: 16 March 1998 / Accepted: 2 February 1999