68Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

PET (positron emission tomography) is a powerful diagnostic and imaging technique which requires short‐lived positron emitting isotopes. The most commonly used are accelerator‐produced ¹¹C and ¹⁸F. An alternative is the use of metallic positron emitters. Among them ⁶⁸Ga deserves special attention because of its availability from long‐lived ⁶⁸Ge/⁶⁸Ga generator systems which render ⁶⁸Ga radiopharmacy independent of an onsite cyclotron. The coordination chemistry of Ga³⁺ is dominated by its hard acid character. A variety of mono‐ and bifunctional chelators have been developed which allow the formation of stable ⁶⁸Ga³⁺complexes and convenient coupling to biomolecules. ⁶⁸Ga coupling to small biomolecules is potentially an alternative to ¹⁸F‐ and ¹¹C‐based radiopharmacy. In particular, peptides targeting G‐protein coupled receptors overexpressed on human tumour cells have shown preclinically and clinically high and specific tumour uptake. Kit‐formulated precursors along with the generator may be provided, similar to the ⁹⁹Mo/^99mTc‐based radiopharmacy, still the mainstay of nuclear medicine. Copyright © 2008 John Wiley & Sons, Ltd.     

Once or twice‐daily,algorithm‐based intravenous cephazolin for home‐based cellulitis treatment

Objective: Cellulitis is a common presentation to the ED and a significant cause of hospitalization that can be managed in hospital‐in‐the‐home programmes. Current clinical‐practice guidelines recommend once or twice‐daily i.v. antibiotics; however, there is an absence of data describing the impact of these guidelines in real‐world practice‐based settings. This study aims to describe the safety and effectiveness of home‐based cellulitis treatment according to an online treatment algorithm. Methods: Over 12 months, 301 patients with a diagnosis of uncomplicated cellulitis requiring i.v. antibiotics and eligible for home‐based therapy completed once‐daily (cephazolin plus probenecid) or twice‐daily (cephazolin alone) treatment, according to the treatment algorithm. Time (days) until non‐progression of cellulitis was the primary outcome measure. Length of stay and treatment‐related side‐effects were also recorded. Results: The mean time until non‐progression was 2.11 (95% confidence interval [CI] 1.98–2.23) days versus 2.13 (95% CI 1.81–2.45) days for the once‐daily (n = 213) and twice‐daily (n = 88) regimens, respectively (P = 0.92, difference in means 0.02 [95% CI ?0.36–0.33]). The corresponding mean length of stay was 6.55 (95% CI 5.96–7.15) days versus 7.67 (95% CI 6.69–8.65) days (P = 0.06, difference in means 1.12 [CI 0.03–1.23]). Treatment‐related side‐effects were reported in 15.5% (33/213 [95% CI 10.6–20.3]) of patients receiving the once‐daily regimen compared with 9.1% (8/88 [95% CI 3.1–15.1]) treated twice‐daily. Application of the once‐daily strategy increased hospital‐in‐the‐home cellulitis‐related treatment capacity by 52% (1396/2688 [95% CI 50–54]). Conclusions: An online decision support algorithm can support the effective use of a once or twice‐daily treatment regimen for uncomplicated cellulitis. This approach can increase the efficiency and capacity of home‐based therapy, resulting in better alignment of treatment options with clinicians and patients' preferences.     

Reconciling evidence‐based medicine and patient‐centred care: defining evidence‐based inputs to patient‐centred decisions

Evidence‐based and patient‐centred health care movements have each enhanced the discussion of how health care might best be delivered, yet the two have evolved separately and, in some views, remain at odds with each other. No clear model has emerged to enable practitioners to capitalize on the advantages of each so actual practice often becomes, to varying degrees, an undefined mishmash of each. When faced with clinical uncertainty, it becomes easy for practitioners to rely on formulas for care developed explicitly by expert panels, or on the tacit ones developed from experience or habit. Either way, these tendencies towards ‘cookbook’ medicine undermine the view of patients as unique particulars, and diminish what might be considered patient‐centred care. The sequence in which evidence is applied in the care process, however, is critical for developing a model of care that is both evidence based and patient centred. This notion derives from a paradigm for knowledge delivery and patient care developed over decades by Dr. Lawrence Weed. Weed's vision enables us to view evidence‐based and person‐centred medicine as wholly complementary, using computer tools to more fully and reliably exploit the vast body of collective knowledge available to define patients’ uniqueness and identify the options to guide patients. The transparency of the approach to knowledge delivery facilitates meaningful practitioner–patient dialogue in determining the appropriate course of action. Such a model for knowledge delivery and care is essential for integrating evidence‐based and patient‐centred approaches.     

Corroborating evidence‐based medicine

Proponents of evidence‐based medicine (EBM) have argued convincingly for applying this scientific method to medicine. However, the current methodological framework of the EBM movement has recently been called into question, especially in epidemiology and the philosophy of science. The debate has focused on whether the methodology of randomized controlled trials provides the best evidence available. This paper attempts to shift the focus of the debate by arguing that clinical reasoning involves a patchwork of evidential approaches and that the emphasis on evidence hierarchies of methodology fails to lend credence to the common practice of corroboration in medicine. I argue that the strength of evidence lies in the evidence itself, and not the methodology used to obtain that evidence. Ultimately, when it comes to evaluating the effectiveness of medical interventions, it is the evidence obtained from the methodology rather than the methodology that should establish the strength of the evidence.     

Measurement equivalence of touch‐screen computerized and paper‐based diabetes‐specific quality‐of‐life questionnaires

Current advances in technology have enabled the development of a computer‐based questionnaire that provides advantages over the paper‐based mode of administration, such as automatic data entry, storage and calculations. However, before implementing a computer‐based questionnaire, its equivalence with the original paper‐based questionnaire must first be demonstrated. The purpose of this study was to evaluate the measurement equivalence of the computerized Diabetes‐Specific Quality‐of‐Life questionnaire (cD‐QOL) with its original paper‐based counterpart. A two‐period crossover design was used in this study. The measurement equivalence was evaluated using quadratic weighted kappa coefficients, intraclass correlations and Cronbach's alpha comparisons. The cD‐QOL was equivalent to its original paper‐based counterpart. Participants preferred the cD‐QOL over the paper‐based questionnaire and reported that it was easy to use.     

Parallel assessment of prolonged neonatal distress by empathy‐based and item‐based scales

Objective: To evaluate the association between the empathy‐based Faces Pain Scale‐Revised (FPS‐R) and the item‐based Neonatal Pain, Agitation and Sedation Scale (N‐PASS) when used to assess prolonged distress in term and preterm infants. Method: Sequential prospective psychometric evaluations of distress, at 4‐h intervals during a 48‐h time period. FPS‐R and N‐PASS were employed in parallel by the nurses in charge in 44 term and preterm newborn infants. Results: During the overall 48‐h observation period, median FPS‐R declined from 6/10 to 2/10 (p < 0.001) while N‐PASS did not change significantly. FPS‐R and N‐PASS showed strong correlation during the first 12 h of observation (R_s = 0.786, p < 0.001). During each of the following 12‐h observation periods, the strength of this association decreased (12–24 h: R_s = 0.781; 24–36 h: R_s = 0.675; 36–48 h: R_s = 0.658) while remaining significant (p < 0.001). However, when used to categorize infants as being in distress or not, the rate of agreement between FPS‐R and N‐PASS showed little variation (0–12 h: 79.6%, 12–24 h: 88.6%; 24–36 h: 89.4%, 36–48 h: 84.9%). Conclusions: In newborn infants serially assessed over 48 h, there is a progressive divergence between FPS‐R and N‐PASS. There is, however, reason to extend the use of the FPS‐R also to the neonatal arena, as the rate of agreement between N‐PASS and FPS‐R to categorize an infant as being in distress or not remains stable. Preference of item‐ or empathy‐based assessment may be a question of personal philosophy rather than medical science.     

Concentration‐independent MRI of pH with a dendrimer‐based pH‐responsive nanoprobe

The measurement of extracellular pH (pH_e) has significant clinical value for pathological diagnoses and for monitoring the effects of pH‐altering therapies. One of the major problems of measuring pH_e with a relaxation‐based MRI contrast agent is that the longitudinal relaxivity depends on both pH and the concentration of the agent, requiring the use of a second pH‐unresponsive agent to measure the concentration. Here we tested the feasibility of measuring pH with a relaxation‐based dendritic MRI contrast agent in a concentration‐independent manner at clinically relevant field strengths. The transverse and longitudinal relaxation times in solutions of the contrast agent (GdDOTA‐4AmP)₄₄‐G5, a G5–PAMAM dendrimer‐based MRI contrast agent in water, were measured at 3 T and 7 T magnetic field strengths as a function of pH. At 3 T, longitudinal relaxivity (r₁) increased from 7.91 to 9.65 mM^?1 s^?1 (on a per Gd³⁺ basis) on changing pH from 8.84 to 6.35. At 7 T, r₁ relaxivity showed pH response, albeit at lower mean values; transverse relaxivity (r₂) remained independent of pH and magnetic field strengths. The longitudinal relaxivity of (GdDOTA‐4AmP)₄₄‐G5 exhibited a strong and reversible pH dependence. The ratio of relaxation rates R₂/R₁ also showed a linear relationship in a pH‐responsive manner, and this pH response was independent of the absolute concentration of (GdDOTA‐4AmP)₄₄‐G5 agent. Importantly, the nanoprobe (GdDOTA‐4AmP)₄₄‐G5 shows pH response in the range commonly found in the microenvironment of solid tumors. Copyright © 2015 John Wiley & Sons, Ltd.     

Evidence‐based medicine as science

Evidence‐based medicine has claimed to be science on a number of occasions, but it is not clear that this status is deserved. Within the philosophy of science, four main theories about the nature of science are historically recognized: inductivism, falsificationism, Kuhnian paradigms, and research programmes. If evidence‐based medicine is science, knowledge claims should be derived using a process that corresponds to one of these theories. This paper analyses whether this is the case. In the first section, different theories about the nature of science are introduced. In the second section, the claim that evidence‐based medicine is science is reinterpreted as the claim that knowledge claims derived from randomized controlled trails and meta‐analyses are science. In the third section, the knowledge claims valued within evidence‐based medicine are considered from the perspective of inductivism, falsificationism, Kuhnian paradigms, and research programmes. In the final section, possible counter arguments are considered. It is argued that the knowledge claims valued by evidence‐based medicine are not justified using inductivism, falsificationism, Kuhnian paradigms, or research programmes. If these are the main criteria for evaluating if something is science or not, evidence‐based medicine does not meet these criteria.     

Recovery of evidence‐based practice

Consumer recovery is now enshrined in the national mental health policy of many countries. If this construct, which stems from the consumer/user/survivor movement, is truly to be the official and formal goal of mental health services, then it must be the yardstick against which evidence‐based practice (EBP) is judged. From a consumer‐recovery perspective, this paper re‐examines aspects of services chosen for study, methodologies, outcomes measures, and standards of evidence associated with EBP, those previously having been identified as deficient and in need of expansion. One of the significant differences between previous investigations and the present study is that the work, writing, perspectives, and advocacy of the consumer movement has developed to such a degree that we now have a much more extensive body of material upon which to critique EBP and inform and support the expansion of EBP. Our examination reinforces previous findings and the ongoing need for expansion. The consumer recovery‐focused direction, resources, frameworks, and approaches identified through the present paper should be used to expand the aspects of services chosen for study, methodologies, outcomes measures, and standards of evidence. This expansion will ultimately enable services to practice in a manner consistent with the key characteristics of supporting personal recovery.     

Underdetermination in evidence‐based medicine

This article explores the philosophical implications of evidence‐based medicine's (EBM's) epistemology in terms of the problem of underdetermination of theory by evidence as expounded by the Duhem–Quine thesis. EBM hierarchies of evidence privilege clinical research over basic science, exacerbating the problem of underdetermination. Because of severe underdetermination, EBM is unable to meaningfully test core medical beliefs that form the basis of our understanding of disease and therapeutics. As a result, EBM adopts an epistemic attitude that is sceptical of explanations from the basic biological sciences, and is relegated to a view of disease at a population level. EBM's epistemic attitude provides a limited research heuristic by preventing the development of a theoretical framework required for understanding disease mechanism and integrating knowledge to develop new therapies. Medical epistemology should remain pluralistic and include complementary approaches of basic science and clinical research, thus avoiding the limited epistemic attitude entailed by EBM hierarchies.