Checklist for the qualitative evaluation of clinical studies with particular focus on external validity and model validity

Background  

It is often stated that external validity is not sufficiently considered in the assessment of clinical studies. Although tools for its evaluation have been established, there is a lack of awareness of their significance and application. In this article, a comprehensive checklist is presented addressing these relevant criteria.     

Application of magnetic resonance imaging to evaluation of femoral neck structure in growing girls.

Conventional density measures by dual-energy X-ray absorptiometry (DXA) are confounded by increases in bone size and do not assess bone geometry. We assessed precision of magnetic resonance imaging (MRI) and used MRI, DXA, and hip structure analysis (HSA) to assess 7-mo changes in bone structure at the femoral neck in 18 prepubertal girls. At baseline, girls were 10.4 (0.5) yr, 144.0 (8.2) cm, and 35.2 (7.0) kg, on average. Total bone and cortical cross-sectional area (ToA and CoA) were calculated from high-resolution T1-weighted MRI oblique axial images of the femoral neck. We used proximal femur DXA scans (Hologic QDR-4500) and the HSA program to estimate bone cross-sectional area (CSA), and calculate section modulus. MRI precision was determined by scanning 10 volunteers (13-46 yr old) three times with and without repositioning. Precision (CVrms) was 2% for ToA and 7% for CoA. Significant correlations were observed between FN area and MRI-derived ToA (r = 0.57, p = 0.013) and CoA (r = 0.47, p = 0.050). There were significant positive changes over 7 mo by both methods. In conclusion, MRI provides useful information on femoral neck bone area in children. The reproducibility of cortical dimensions at the femoral neck needs improvement through technical modifications and appropriate analysis software.     

Building a relationship: communications and relationships between staff and stroke patients on a rehabilitation ward

Communications among staff and patients on a stroke rehabilitation ward form the focus of this article, which reports on some aspects of a larger study using a grounded theory approach. Tape-recorded interviews were transcribed and analysed concurrently according to recommendations for the approach. A main theme entitled building a relationship was identified, and this process was found to occur in a context varying from participative at one end of a continuum to hierarchical at the other. Building a relationship was found to be influenced by role, personal qualities and organizational context. Appropriate relationships between role-holders were subject to negotiation, leading to a resulting congruence or incongruence between participants' expectations of each other and their roles. Personal qualities were brought into play in the process, with patients' views of staff and staff views of patients both being influential. Some of these views seemed to parallel what has been described in earlier literature as ‘the sick role’ and the labelling of patients as ‘good’ or ‘bad’. Responses to personal qualities led to nurses ascribing meaning to patients' behaviour in terms of adjustment to their stroke, giving time to them to help them to adjust, and withdrawal and handing over to other staff if this strategy failed. Organizational context also had an influence on building a relationship, with time constraints being identified particularly by nurses, and the need to fit in the most essential aspects of care. Place was also important, in that nurses were confined to the ward as a work location, whereas other therapists and doctors worked in other places and sometimes had the facility to take patients off the ward to concentrate on therapy. The findings are discussed against the background of related literature and the conclusion is drawn that the crucial role of nurses in rehabilitation is not recognized and valued, and that shortages of resources - especially suitably qualified and trained nursing staff- are a negative influence on building the relationships which are vital to successful rehabilitation.     

Company finds emerging niche for its global-rescue business

A Singapore-based company with a subsidiary office in Seattle offers emergency medical assistance to employees of North American companies operating in Asia and South America. The company offers routine medical service and emergency evacuation around the clock.     

The public health and brief interventions for excessive alcohol consumption: The british experience

Widely disseminated brief interventions against excessive drinking, as part of the new public health movement, have a potentially crucial role in reducing alcohol-related harm on a national scale. However, a number of conceptual problems and practical barriers to progress in this area can already be identified. This article focuses on the British experience of research and implementation of community-based brief interventions, which is longer than that of other countries, as a means of discussing these problems. Rather than being pessimistic about the possible impact of brief interventions, the article is based on the assumption that it is only by clearly recognizing and solving such problems that the potential of brief interventions in the alcohol field will be fully realized.     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.     

Renal clearance and protein binding of melphalan in patients with cancer

Summary The renal clearance of melphalan and the fraction unbound in plasma were determined after intravenous infusion of 5 mg/m² over 5 min in nine patients with cancer to obtain information regarding the mechanism of renal handling of melphalan. Four of the patients underwent bone marrow transplantation and also received an IV dose of 220 mg/m². Total melphalan clearance after the 5 mg/m² dose ranged from 66.0 to 272 ml/min per m²; the percentage of the dose excreted unchanged in urine, from 2.5% to 92.8%; renal clearance, from 4.1 to 188 ml/min per m²; the fraction unbound in plasma, from 0.0598 to 0.460; and t_1/2, from 39.4 to 84.3 min. Unbound melphalan clearance and renal clearance calculated from the unbound fraction in plasma for each patient ranged from 441 to 3356 ml/min per m² and 15 to 961 ml/min per m² respectively and were not related to serum albumin, serum creatinine or creatinine clearance. The percentage of the dose exctreted and melphalan renal clearance were not related to urine flow. There was evidence of active secretion of melphalan in the kidney an possible reabsorption. There were no significant paired differences in melphalan disposition between the high- and low-dose studies. Highly variable renal clearance involving active secretion may contribute in part to large interpatient differences in the total plasma clearance of melphalan in patients with cancer.This study was supported by a grant from The Queen Elizabeth Hospital Research Foundation     

Aspects of three dimensional reconstruction for a multi ring positron tomography

An important feature of multi ring positron tomographs is the inter plane septa, the purpose of which is to reduce random and scattered coincidences. In general, such septa also eliminate the coincidence lines of response between pairs of detectors more than one ring apart. The operation of a camera without septa must result in an increase not only in the true coincidence rate, but also in the singles, and therefore in the dead time and randoms rate, and in the scattered coincidences. A configuration option in the coincidence hardware of the 8 ring, 15 slice ECAT 931/08-12 enables a full set of 64 sinograms to be acquired when the septa are removed. The detector normalisation and transmission data for studies with the septa out can be obtained using a rotating pin source. To take maximum advantage of the additional signal, the emission data must be reconstructed using a fully three dimensional reconstruction algorithm. This paper presents an analysis of some phantom studies acquired without septa and reconstructed in three dimensions. The results are compared with data acquired with septa for the same phantoms imaged under similar conditions. It is found that, with the septa removed, the signal to noise for a uniform, 20 cm diameter cylinder improves by a factor of 2.8 in the centre of the field of view, whereas in regions distant from the centre in the axial direction, the signal to noise decreases due to the increase in scatter and randoms. An improvement in signal to noise is observed in 6 cm of the 10 cm axial length of the tomograph.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

Radiation therapy in the management of low-grade supratentorial astrocytomas

The records of 167 patients with grade 1 or 2 supratentorial pilocytic astrocytomas (41 patients), ordinary astrocytomas (91 patients), or mixed oligoastrocytomas (35 patients) diagnosed between 1960 and 1982 are retrospectively reviewed. The extent of surgical tumor removal was gross total or radical subtotal in 33 patients (20%) and subtotal or biopsy only in the remaining 134 patients (80%). Postoperative radiation therapy was given to 139 (83%) of the 167 patients, with a median dose of 5000 cGy (range 600 to 6500 cGy). Multivariate analysis revealed that a pilocytic histology was the most significant prognostic variable associated with a good survival. The 5- and 10-year survival rates were, respectively, 85% and 79% for the 41 patients with pilocytic astrocytomas compared to 51% and 23% for the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas. Postoperative irradiation did not appear to be associated with improved survival times in the patients with pilocytic astrocytomas; however, in the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas, those who received "high-dose" radiation (greater than or equal to 5300 cGy) had significantly better survival times than those who received "low-dose" radiation (less than 5300 cGy) or surgery alone. The 5- and 10-year survival rates were, respectively, 68% and 39% for the 35 patients receiving high-dose radiation, 47% and 21% for the 67 receiving low-dose radiation, and 32% and 11% for the 19 treated with surgery alone. The survival rate was poor for the 23 patients with ordinary astrocytomas and oligoastrocytomas who underwent gross total or radical subtotal tumor removal (14 of whom were also irradiated): 52% at 5 years and 21% at 10 years, with 19 of 23 patients developing tumor progression and dying 1 to 12 years postoperatively. In contrast, all 10 patients with pilocytic astrocytomas who had gross total or radical subtotal tumor removal alone were long-term survivors, with follow-up periods of about 4 to 25 years.