Cross-sectional associations between short and mid-term blood pressure variability, cognition, and vascular stiffness in older adults.

Background: High blood pressure variability (BPV), particularly in older age, appears to be an independent risk factor for incident dementia. The current study aimed to investigate the association between different BPV measures (short- and mid-term BPV including circadian patterns) and cognitive functioning as well as vascular stiffness measures to better understand the role that BPV plays in cognitive impairment. Methods: 70 older adults (60-80-year-olds) without dementia completed a cognitive test battery and had their blood pressure (BP) assessed via a 24-hour ambulatory BP monitor (divided into sleep and wake for short-term BPV) and 4-day morning and evening home-based BP monitor (for day-to-day BPV). Arterial stiffness was evaluated via pulse wave analysis and pulse wave velocity (PWV) and cerebrovascular pulsatility was assessed via transcranial doppler sonography of the middle cerebral arteries. Results: High systolic as well as diastolic short- and mid-term BPV were associated with poorer cognitive functioning, independent of the mean BP. Higher short-term BPV was associated with poorer attention and psychomotor speed, whilst day-to-day BPV was negatively linked with executive functioning. Circadian BP patterns (dipping and morning BP surge) showed no significant relationships with cognition after adjusting for covariates. Higher systolic short-term BPV was associated with higher arterial stiffness (PWV) and higher diastolic day-to-day BPV was linked with lower arterial stiffness. No significant associations between BPV measures and cerebrovascular pulsatility were present. Conclusion: High BPV, independently of the mean BP, is associated with lower cognitive performance and increased arterial stiffness in older adults without clinically-relevant cognitive impairment. This highlights the role of systolic and diastolic BPV as a potential early clinical marker for cognitive impairment.

Prostate cancer induced bone pain: pathobiology, current treatments and pain responses from recent clinical trials.

PURPOSE: Metastatic spread of prostate cancer to the skeleton may result in debilitating bone pain. In this review, we address mechanisms underpinning the pathobiology of metastatic prostate cancer induced bone pain (PCIBP) that include sensitization and sprouting of primary afferent sensory nerve fibres in bone. We also review current treatments and pain responses evoked by various treatment modalities in clinical trials in this patient population. METHODS: We reviewed the literature using PubMed to identify research on the pathobiology of PCIBP. Additionally, we reviewed clinical trials of various treatment modalities in patients with PCIBP with pain response outcomes published in the past 7 years. RESULTS: Recent clinical trials show that radionuclides, given either alone or in combination with chemotherapy, evoked favourable pain responses in many patients and a single fraction of local external beam radiation therapy was as effective as multiple fractions. However, treatment with chemotherapy, small molecule inhibitors and/or immunotherapy agents, produced variable pain responses but pain response was the primary endpoint in only one of these trials. Additionally, there were no published trials of potentially novel analgesic agents in patients with PCIBP. CONCLUSION: There is a knowledge gap for clinical trials of chemotherapy, small molecule inhibitors and/or immunotherapy in patients with PCIBP where pain response is the primary endpoint. Also, there are no novel analgesic agents on the horizon for the relief of PCIBP and this is an area of large unmet medical need that warrants concerted research attention.

Long-Chain Omega-3 Fatty Acid Intake Is Associated with Age but not Cognitive Performance in an Older Australian Sample.

BACKGROUND: Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are essential nutrients and may be capable of delaying age-related cognitive decline. However, previous studies indicate that Australians are not meeting recommendations for LCn-3 PUFA intake. The current study therefore examined LCn-3 PUFA intake in an older Australia sample, as well as associations between LCn-3 PUFA intake and cognitive function. METHODS: Cross-sectional data were collected from 90 adults aged 50 to 80 years. LCn-3 PUFA intake was assessed using a food frequency questionnaire and red blood cell fatty acid profiles were used to calculate the Omega-3 Index (RBC n-3 index). Cognitive function was measured using Addenbrooke's Cognitive Examination-III. RESULTS: Positive associations were observed between age and RBC n-3 index (b=0.06, 95% CI: 0.01 - 0.10, P=0.01), and age and LCn-3 PUFA intake from fish oil capsules (b=17.5, 95% CI: 2.4 - 32.5 mg/day, P=0.02). When adjusting for LCn-3 PUFA from fish oil capsules, the association between age and RBC n-3 index was no longer significant. No associations were observed between LCn-3 PUFA intake and cognitive function. CONCLUSION: LCn-3 PUFA and fish oil consumption increased with age in this sample of older Australians, particularly due to supplement intake. However, LCn-3 PUFA intake was not associated with cognitive function.

Combined spinal/caudal catheter anesthesia: extending the boundaries of regional anesthesia for complex pediatric urological surgery.

BACKGROUND: Spinal anesthesia (SA) is an established anesthetic technique for short outpatient pediatric urological cases. To avoid general anesthesia (GA) and expand regional anesthetics to longer and more complex pediatric surgeries, the authors began a program using a combined spinal/caudal catheter (SCC) technique. STUDY DESIGN: The authors retrospectively reviewed the charts of all patients scheduled for surgery under SCC between December 2016 and April 2018 and recorded age, gender, diagnosis, procedure, conversion to GA/airway intervention, operative time, neuraxial and intravenous medications administered, complications, and outcomes. The SCC technique typically involved an initial intrathecal injection of 0.5% isobaric bupivacaine followed by placement of a caudal epidural catheter. At the discretion of the anesthesiologist, patients received 0.5 mg per kilogram of oral midazolam approximately 30 min prior to entering the operating room. One hour after the intrathecal injection, 3% chloroprocaine was administered via the caudal catheter to prolong the duration of surgical block. Intra-operative management included either continuous infusion or bolus dosing of dexmedetomidine, as needed, for patient comfort and to optimize surgical conditions. Prior to removal of caudal catheter in the post-anesthesia care unit, a supplemental bolus dose of local anesthesia was given through the catheter to provide prolonged post-operative analgesia. RESULTS: Overall, 23 children underwent attempted SCC. SA was unsuccessful in three patients, and surgery was performed under GA. The remaining 20 children all had successful SCC placement. There were 11 girls and nine boys, with a mean age of 16.5 months (3.3-43.8). Surgeries performed under SCC included seven ureteral reimplantations, two ureterocele excisions/reimplantations, two megaureter repairs, four first-stage hypospadias repairs, one distal hypospadias repair, one second-stage hypospadias repair, two feminizing genitoplasties, and one open pyeloplasty. Average length of surgery was 109 min (range 63-172 min). Pre-operative midazolam was given in 13/20 (65%). All SCC patients were spontaneously breathing room air during the operation, and there were no airway interventions. Only one SCC patient received opioids intra-operatively. There were no intra-operative or perioperative complications. DISCUSSION: This pilot study shows that the technique of SCC allows one to do more complex urologic surgery under regional anesthesia than what would be possible under pure SA alone. The main limitations of the study include the relatively small number of patients and the small median length of the operative procedures. As a proof of concept, however, this does show that complex genital surgery bladder level procedures such as ureteral reimplantation can be performed under regional anesthesia. CONCLUSION: SCC allows for more complex surgeries to be performed exclusively under regional anesthesia, thus obviating the need for airway intervention, minimizing or eliminating the use of opioids, and thus avoiding known and potential risks associated with GA. The latter is of particular importance given current concerns regarding hypothetical neurocognitive effects of GA on children aged below 3 years.

Efficacy of neutralizing buffered peptone water for recovery of Salmonella, Campylobacter, and Enterobacteriaceae from broiler carcasses at various points along a commercial immersion chilling process with peroxyacetic acid.

In 2016, USDA-Food Safety and Inspection Service began using a neutralizing buffered peptone water (nBPW) to rinse broiler carcasses for Salmonella and Campylobacter performance standard testing. The nBPW contains standard buffered peptone water (BPW) with compounds to neutralize residual antimicrobials that may be transferred from the carcass to the sample rinsate. However, a direct comparison of nBPW and BPW on carcasses commercially treated with antimicrobials has not been conducted. On 3 replicate days in a commercial broiler processing plant, an immersion chilling biomap using whole carcass rinse samples taken prior to any chilling treatment (30), after pre-chill treatment (30), after primary chill (30), after secondary chill (30), after post-chill treatment (50), and after post-chill treatment without the pre-chill treatment (49) were tested. Carcasses were rinsed with either BPW (without neutralizer) or nBPW. Rinsates were sampled for Salmonella and Campylobacter prevalence and both Enterobacteriaceae (EB) prevalence and counts. No significant differences were observed between sampling sites or rinse media for Salmonella due to an overall low prevalence (4 positive/219 samples). Campylobacter prevalence significantly decreased from prior to chilling (93%) to after all chilling steps (47%) as anticipated (P < 0.0001); however, overall significantly fewer Campylobacter positive carcasses were detected when nBPW was used (55%) in comparison to BPW (70%, P = 0.0258). Both EB prevalence and counts significantly decreased (both P < 0.0001) from prior to chilling (100%, 2.35 log10 CFU/mL) through after all chilling steps (52%, 0.47 log10 CFU/mL). The use of nBPW versus BPW did not impact EB prevalence; however, samples rinsed with nBPW had significantly higher overall counts (1.26 vs. 1.00 log10 CFU/mL, P = 0.0134). The results from this study indicate that the use of a PAA pre-chill treatment did not significantly impact bacteria recovery following all chilling steps. The use of nBPW was effective in neutralizing residual PAA in carcass rinsates when sampling for EB counts; however, nBPW may lessen the ability to detect Campylobacter in these same samples.

Cognitive deficits associated with a high-fat diet and insulin resistance are potentiated by overexpression of ecto-nucleotide pyrophosphatase phosphodiesterase-1.

There is growing evidence that over consumption of high-fat foods and insulin resistance may alter hippocampal-dependent cognitive function. To study the individual contributions of diet and peripheral insulin resistance to learning and memory, we used a transgenic mouse line that overexpresses ecto-nucleotide pyrophosphatase phosphodiesterase-1 in adipocytes, which inhibits the insulin receptor. Here, we demonstrate that a model of peripheral insulin resistance exacerbates high-fat diet induced deficits in performance on the Morris Water Maze task. This finding was then reviewed in the context of the greater literature to explore potential mechanisms including triglyceride storage, adiponectin, lipid composition, insulin signaling, oxidative stress, and hippocampal signaling. Together, these findings further our understanding of the complex relationship among peripheral insulin resistance, diet and memory.

Preclinical modeling of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematological clonal disorders. Here, we have tested the bone marrow (BM) cells from 38 MDS patients covering all risk groups in two immunodeficient mouse models: NSG and NSG-S. Our data show comparable level of engraftment in both models. The level of engraftment was patient specific with no correlation to any specific MDS risk group. Furthermore, the co-injection of mesenchymal stromal cells (MSCs) did not improve the level of engraftment. Finally, we have developed an in vitro two-dimensional co-culture system as an alternative tool to in vivo. Using our in vitro system, we have been able to co-culture CD34+ cells from MDS patient BM on auto- and/or allogeneic MSCs over 4 weeks with a fold expansion of up to 600 times. More importantly, these expanded cells conserved their MDS clonal architecture as well as genomic integrity.

Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes.

Although next-generation sequencing has allowed for the detection of somatic mutations in myelodysplastic syndromes (MDS), the clinical relevance of variant allele frequency (VAF) for the majority of mutations is unknown. We profiled TP53 and 20 additional genes in our training set of 219 patients with MDS or secondary acute myeloid leukemia with findings confirmed in a validation cohort. When parsed by VAF, TP53 VAF predicted for complex cytogenetics in both the training (P=0.001) and validation set (P<0.0001). MDS patients with a TP53 VAF > 40% had a median overall survival (OS) of 124 days versus an OS that was not reached in patients with VAF <20% (hazard ratio (HR), 3.52; P=0.01) with validation in an independent cohort (HR, 4.94, P=0.01). TP53 VAF further stratified distinct prognostic groups independent of clinical prognostic scoring systems (P=0.0005). In multivariate analysis, only a TP53 VAF >40% was an independent covariate (HR, 1.61; P<0.0001). In addition, SRSF2 VAF predicted for monocytosis (P=0.003), RUNX1 VAF with thrombocytopenia (P=0.01) and SF3B1 with ringed sideroblasts (P=0.001). Together, our study indicates that VAF should be incorporated in patient management and risk stratification in MDS.

High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS).

Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have provided important biological and prognostic information; however, frequent BM sampling in older patients has been associated with significant morbidity. Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the concordance of genetic abnormalities in BM and peripheral blood (PB) samples concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108 (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB karyotype. The median copy number (CN) for deletions was significantly lower in BM (CN:1.4 (1-1.9)) than in PB (CN:1.5 (1-1.95), P<0.001). Using TGS, 71% (130/183) patients had BM somatic mutations with 95% (124/130) having identical mutations in PB. The mutant allele burden was lower in PB (median 27% (1-96%)) compared with BM (median 29% (1-100%); P=0.14) with no significant difference in the number, types of mutations or World Health Organization subtype. In all patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and PB, shared abnormalities were always present irrespective of treatment status. Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A karyotype and mutations in PB, thus enabling frequent assessment of response to treatment and disease evolution especially in patients with fibrotic or hypocellular marrows.

The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes.

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progression-free survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise the largest MDS R72P SNP analysis.

Exercise-induced oxidative stress: the effects of ß-alanine supplementation in women.

The purpose of this study was to evaluate the effects of ß-alanine supplementation on markers of oxidative stress. Twenty-four women (age: 21.7±2.1 years; VO2max: 2.6±0.3 l min(-1)) were randomly assigned, in a double-blind fashion, to a ß-alanine (BA, 2×800 mg tablets, 3× daily; CarnoSyn®; n=13) or placebo (PL, 2×800 mg maltodextrin tablets, 3× daily; n=11) group. A graded oxygen consumption test (VO2max) was performed to evaluate VO2max, time to exhaustion, ventilatory threshold and establish peak velocity (PV). A 40-min treadmill run was used to induce oxidative stress. Total antioxidant capacity, superoxide dismutase, 8-isoprostane (8ISO) and reduced glutathione were measured. Heart rate and ratings of perceived exertion were recorded during the 40 min run. Separate three- [4×2×2; acute (base vs. IP vs. 2 vs. 4 h)×chronic (pre- vs. post-)×treatment (BA vs. PL)] and two- [2×2; time (pre-supplement vs. post-supplement)×treatment (BA vs. PL)] way ANOVAs were used for analyses. There was a significant increase in VO2max (p=0.009), independent of treatment, with no significant changes in TTE (p=0.074) or VT (p=0.344). Ratings of perceived exertion values were significantly improved from pre- to post-supplementation for the BA group only at 40 min (p=0.02). The ANOVA model demonstrated no significant treatment effects on oxidative stress. The chronic effects of BA supplementation demonstrated little antioxidant potential, in women, and little influence on aerobic performance assessments.

Ergolytic/ergogenic effects of creatine on aerobic power.

This study evaluated the effects of creatine (Cr) loading and sex differences on aerobic running performance. 27 men (mean±SD; age: 22.2±3.1 years, ht: 179.5±8.7 cm, wt: 78.0±9.8 kg) and 28 women (age: 21.2±2.1 years, ht: 166.0±5.8 cm, wt: 63.4±8.9 kg) were randomly assigned to either creatine (Cr, di-creatine citrate; n=27) or a placebo (PL; n=28) group, ingesting 1 packet 4 times daily (total of 20 g/day) for 5 days. Aerobic power (maximal oxygen consumption: VO2max) was assessed before and after supplementation using open circuit spirometry (Parvo-Medics) during graded exercise tests on a treadmill. 4 high-speed runs to exhaustion were conducted at 110, 105, 100, and 90% of peak velocity to determine critical velocity (CV). Distances achieved were plotted over times-to-exhaustion and linear regression was used to determine the slopes (critical velocity, CV) assessing aerobic performance. The results indicated that Cr loading did not positively or negatively influence VO2max, CV, time to exhaustion or body mass (p>0.05). These results suggest Cr supplementation may be used in aerobic running activities without detriments to performance.

Acute effects of passive stretching vs vibration on the neuromuscular function of the plantar flexors.

This study examined the acute effects of passive stretching (PS) vs prolonged vibration (VIB) on voluntary peak torque (PT), percent voluntary activation (%VA), peak twitch torque (PTT), passive range of motion (PROM), musculotendinous stiffness (MTS), and surface electromyographic (EMG) and mechanomyographic (MMG) amplitude of the medial gastrocnemius (MG) and soleus (SOL) muscles during isometric maximal voluntary contractions (MVCs) of the plantar flexors. Fifteen healthy men performed the isometric MVCs and PROM assessments before and after 20 min of PS, VIB, and a control (CON) conditions. There were 10% and 5% decreases in voluntary PT, non-significant 3% and 2% decreases in %VA, 9-23% decreases in EMG amplitude of the MG and SOL after the PS and VIB, respectively, with no changes after the CON. PROM increased by 19% and MTS decreased by 38% after the PS, but neither changed after the VIB or CON conditions. Both PS and VIB elicited similar neural deficits (i.e., gamma loop impairment) that may have been responsible for the strength losses. However, mechanical factors related to PROM and MTS cannot be ruled out as contributors to the stretching-induced force deficit.

Effects of creatine supplementation on the onset of neuromuscular fatigue threshold and muscle strength in elderly men and women (64 - 86 years).

OBJECTIVES: This study examined the effects of 14 days of creatine supplementation on the physical working capacity at fatigue threshold (PWCFT), maximal isometric grip strength (GRIP), sit-to-stand (STS), and body weight (BW) in elderly men and women. DESIGN: Using a double blind cross-over design, fifteen men (n = 7) and women (n = 8) (age +/- SD = 74.5 +/- 6.4 yrs) were randomly assigned to either the creatine (CR) (20g.d-1 during week 1 decreasing to 10g.d-1 at week 2) or Placebo (PL) group. After a 4 to 6 week washout period, the subjects were assigned the other treatment. Before (pre) and after (post) the supplementation period, participants performed a discontinuous, cycle ergometry test to determine the PWCFT. In addition, subjects performed STS, GRIP, BW test prior to and post treatment. SETTING: Southeastern part of the United States. RESULTS: Significant increases in GRIP (6.7%) and PWCFT (15.6%) from pre- to post-supplementation were found for the CR (p < 0.05) treatment, but no change for the PL treatment was observed. However, no significant change (p superior 0.05) was noted for STS or BW for either treatment. CONCLUSION: These findings suggest that 14 days of CR supplementation may increase upper body grip strength and increase physical working capacity by delaying neuromuscular fatigue in the elderly men and women in this study. While more research is needed, CR supplementation may improve upper body grip strength and lower body muscle endurance which may be important for maintaining health and independent living in elderly men and women.

GST CYP and PON1 polymorphisms in farmers attributing ill health to organophosphate-containing sheep dip.

Previously we reported that in sheep dippers exposed to organophosphates the frequency of paraoxonase (PON1) polymorphisms differed between those with or without self-reported ill health. We have now examined whether polymorphisms in other genes involved in xenobiotic metabolism alter disease risk in this population. There were elevated but non-significant risks associated with the CYP2D6 WT genotype (odds ratio (OR) 1.47, 95% CI 0.83-2.60), or a GSTP1*B or *C allele (OR 1.37, 95% CI 0.88-2.01) or being GSTM1*2/GSTT1*2 homozygous (OR 1.61, 95% CI 0.74-3.48). Similar results were generally obtained after the exclusion of subjects to obtain a more homogenous case-referent population: for double null GSTM1 and GSTT1 homozygotes the OR was 2.06 (95% CI 0.85-2.04). In those also likely to have been exposed to diazinon, risks associated with a GSTP1*B or *C allele (OR 1.82, 95% CI 0.92-3.63) or a GSTM1*2/GSTT1*2 homozygous (OR 2.60, 95% CI 0.72-10.42) were elevated but not to a significant extent. Risk associated with PON1 genotype and phenotype varied with CYP2D6 and GSTP1 genotype but not consistently with a priori hypotheses. Further work is necessary to delineate more clearly pathways of organophosphate activation and non-PON1 pathways of detoxification and to confirm whether CYP and GST polymorphisms alter disease risk in populations exposed to organophosphates.

Paraoxonase polymorphisms and self-reported chronic ill-health in farmers dipping sheep.

BACKGROUND: Serum paraoxonase (PON1) provides protection against organophosphate induced toxicity. Recently we reported that the frequency of paraoxonase polymorphisms in sheep dippers with self-reported chronic ill-health differed from that in dippers with a similar dipping history but no ill-health. As these analyses may have included subjects with conditions unrelated to organophosphate exposure, the aim of this study was to examine whether the risk associated with PON1 polymorphisms varied using a more homogenous case and referent population. METHODS: Each subject completed a detailed symptom questionnaire and their general practitioner was asked whether there was any history of neurological disease that could be confused with the effects of organophosphate poisoning. Subjects were then excluded both on clinical grounds and where identified as atypical on discriminant analysis. RESULTS: Risk associated with the PON1 192 and 55 genotypes altered little with these changes in the population. CONCLUSIONS: These findings are consistent with the hypothesis that organophosphates contribute to the self-reported ill-health of sheep dippers.

Gene therapy progress and prospects: gene therapy of lysosomal storage disorders.

Despite disappointments with early clinical studies, there is continued interest in the development of gene therapy for the group of metabolic diseases referred to as lysosomal storage disorders (LSDs). The LSDs are monogenic and several small and large, representative animal models of the human diseases are available. Further, the successful reconstitution of only low and unregulated tissue levels of the affected lysosomal enzymes are expected to be sufficient to correct the disease at least in the case of some of the LSDs. For these reasons, they are perceived as good models for the evaluation of different gene delivery vectors and of different strategies for treating chronic genetic diseases by gene transfer. In this review, we will highlight the progress that has been made over the past 2 years in preclinical research for this group of disorders and speculate on future prospects.

Evaluation of inherent performance of intelligent medical decision support systems: utilising neural networks as an example.

Researchers who design intelligent systems for medical decision support, are aware of the need for response to real clinical issues, in particular the need to address the specific ethical problems that the medical domain has in using black boxes. This means such intelligent systems have to be thoroughly evaluated, for acceptability. Attempts at compliance, however, are hampered by lack of guidelines. This paper addresses the issue of inherent performance evaluation, which researchers have addressed in part, but a Medline search, using neural networks as an example of intelligent systems, indicated that only about 12.5% evaluated inherent performance adequately. This paper aims to address this issue by concentrating on the possible evaluation methodology, giving a framework and specific suggestions for each type of classification problem. This should allow the developers of intelligent systems to produce evidence of a sufficiency of output performance evaluation.

Implementation of intelligent decision support systems in health care.

The full implementation of any intelligent system in health care, which is designed for decision support, has several stages, from initial problem identification through development and, finally, cost-benefit analysis. Central to this is formal objectivist evaluation with its core component of inherent performance of the outputs from these systems. A Medline survey of one type of intelligent system is presented, which demonstrates that this issue is not being addressed adequately. Lack of criteria for dealing with the outputs from these "black box" systems to prescribe adequate levels of inherent performance may be preventing their being accepted by those in the health-care domain and, thus, their being applied widely in the field.

Performance evaluation of artificial intelligence classifiers for the medical domain.

The application of artificial intelligence systems is still not widespread in the medical field, however there is an increasing necessity for these to handle the surfeit of information available. One drawback to their implementation is the lack of criteria or guidelines for the evaluation of these systems. This is the primary issue in their acceptability to clinicians, who require them for decision support and therefore need evidence that these systems meet the special safety-critical requirements of the domain. This paper shows evidence that the most prevalent form of intelligent system, neural networks, is generally not being evaluated rigorously regarding classification precision. A taxonomy of the types of evaluation tests that can be carried out, to gauge inherent performance of the outputs of intelligent systems has been assembled, and the results of this presented in a clear and concise form, which should be applicable to all intelligent classifiers for medicine.