Optimal evidence in difficult settings: improving health interventions and decision making in disasters.

Martin Gerdin and colleagues argue that disaster health interventions and decision-making can benefit from an evidence-based approach Please see later in the article for the Editors' Summary.

Cost implications of implementing NICE guideline on chest pain in rapid access chest pain clinics: an audit and cost analysis.

BACKGROUND: Implementing the recently published National Institute for Health and Clinical Excellence (NICE) clinical guideline on chest pain (CG95) in rapid access chest pain clinics (RACPCs) could significantly impact on overall cost, while introducing new technology like cardiac computed tomography (CT) scanning. With the National Health Service (NHS) under pressure to make £20 billion savings, applying CG95 in RACPCs could be challenging. An audit enabled us to assess the cost implications. METHODS: A retrospective audit was performed of 204 consecutive cases attending Croydon RACPC from 13 July to 21 September 2010, on risk factors, demographics and planned first-line investigations. CG95 and three alternative strategies were mapped on the sample, and the estimated cost and volume of first-line investigations were compared with actual RACPC activities and costs. RESULTS: Application of CG95 resulted in significant increases in cost and volume of functional testing, cardiac CT scan angiography and invasive coronary angiography, with 42-43% overall cost increases. The application of three alternative strategies resulted in annual cost increases ranging from 0.1 to 33%. An alternative cost analysis showed annual savings of up to 24%. CONCLUSIONS: Implementing NICE CG95 can significantly increase the cost of RACPCs but alternative strategies could enable the introduction of new technology without significant cost increases and even significant savings.

Recent developments in geriatric psychopharmacology.

INTRODUCTION: There is a tremendous growing need to address the burden of geriatric psychiatric disorders. Recent developments relevant to geriatric psychiatry have focused on Alzheimer's disease (AD), severe/refractory depression, and cancer/end of life care. AREAS COVERED: This is a non-systematic, narrative review (databases and websites for search: PubMed, Google Scholar, Medscape, ClinicalTrials.gov; focusing on the last 6 years), and covers developments in disease-modifying therapies for AD, diagnostic radiotracers for AD, medications for neuropsychiatric symptoms of dementia, ketamine/esketamine, psychedelics, and cannabinoids. EXPERT OPINION: The focus of on-going trials of anti-amyloid agents has been on individuals with very early stage AD; several agents are under phase 3 investigation, and aducanumab is under FDA review. Amyloid and tau PET scans have been approved by the FDA to assist in the diagnoses of AD. Promising pharmaceuticals for neuropsychiatric symptoms of dementia include pimavanserin, brexpiprazole, escitalopram, dextromethorphan/quinidine, and lithium. Esketamine, although approved for treatment-resistant depression in general adults, failed to demonstrate efficacy in elderly patients in a phase 3 trial. There is preliminary evidence for benefit of psychedelic-assisted psychotherapy in end-of-life and cancer-related depression/anxiety. Evidence for the use of cannabinoids is currently lacking.

Chronic hepatitis B virus case-finding in UK populations born abroad in intermediate or high endemicity countries: an economic evaluation.

OBJECTIVES: The majority (>90%) of new or undiagnosed cases of hepatitis B virus (HBV) in the UK are among individuals born in countries with intermediate or high prevalence levels (≥2%). We evaluate the cost-effectiveness of increased HBV case-finding among UK migrant populations, based on a one-time opt out case-finding approach in a primary care setting. DESIGN: Cost-effectiveness evaluation. A decision model based on a Markov approach was built to assess the progression of HBV infection with and without treatment as a result of case-finding. The model parameters, including the cost and effects of case-finding and treatment, were estimated from the literature. All costs were expressed in 2017/2018 British Pounds (GBPs) and health outcomes as quality-adjusted life-years (QALYs). INTERVENTION: Hepatitis B virus case-finding among UK migrant populations born in countries with intermediate or high prevalence levels (≥2%) in a primary care setting compared with no intervention (background testing). RESULTS: At a 2% hepatitis B surface antigen (HBsAg) prevalence, the case-finding intervention led to a mean incremental cost-effectiveness ratio of £13 625 per QALY gained which was 87% and 98% likely of being cost-effective at willingness to pay (WTP) thresholds of £20 000 and £30 000 per additional QALY, respectively. Sensitivity analyses indicated that the intervention would remain cost-effective under a £20 000 WTP threshold as long as HBsAg prevalence among the migrant population is at least 1%. However, the results were sensitive to a number of parameters, especially the time horizon and probability of treatment uptake. CONCLUSIONS: HBV case-finding using a one-time opt out approach in primary care settings is very likely to be cost-effective among UK migrant populations with HBsAg prevalence ≥1% if the WTP for an additional QALY is around £20 000.

Singular value based characterization and analysis of thermal patches for early breast abnormality detection.

The purpose of this study is to develop a novel breast abnormality detection system by utilizing the potential of infrared breast thermography (IBT) in early breast abnormality detection. Since the temperature distributions are different in normal and abnormal thermograms and hot thermal patches are visible in abnormal thermograms, the abnormal thermograms possess more complex information than the normal thermograms. Here, the proposed method exploits the presence of hot thermal patches and vascular changes by using the power law transformation for pre-processing and singular value decomposition to characterize the thermal patches. The extracted singular values are found to be statistically significant (p < 0.001) in breast abnormality detection. The discriminability of the singular values is evaluated by using seven different classifiers incorporating tenfold cross-validations, where the thermograms of the Department of Biotechnology-Tripura University-Jadavpur University (DBT-TU-JU) and Database of Mastology Research (DMR) databases are used. In DMR database, the highest classification accuracy of 98.00% with the area under the ROC curve (AUC) of 0.9862 is achieved with the support vector machine using polynomial kernel. The same for the DBT-TU-JU database is 92.50% with AUC of 0.9680 using the same classifier. The comparison of the proposed method with the other reported methods concludes that the proposed method outperforms the other existing methods as well as other traditional feature sets used in IBT based breast abnormality detection. Moreover, by using Rank1 and Rank2 singular values, a breast abnormality grading (BAG) index has also been developed for grading the thermograms based on their degree of abnormality.

Designing of Ground-Truth-Annotated DBT-TU-JU Breast Thermogram Database Toward Early Abnormality Prediction.

The advancement of research in a specific area of clinical diagnosis crucially depends on the availability and quality of the radiology and other test related databases accompanied by ground truth and additional necessary medical findings. This paper describes the creation of the Department of Biotechnology-Tripura University-Jadavpur University (DBT-TU-JU) breast thermogram database. The objective of creating the DBT-TU-JU database is to provide a breast thermogram database that is annotated with the ground-truth images of the suspicious regions. Along with the result of breast thermography, the database comprises of the results of other breast imaging methodologies. A standard breast thermogram acquisition protocol suite comprising of several critical factors has been designed for the collection of breast thermograms. Currently, the DBT-TU-JU database contains 1100 breast thermograms of 100 subjects. Due to the necessity of evaluating any breast abnormality detection system, this study emphasizes the generation of the ground-truth images of the hotspot areas, whose presence in a breast thermogram signifies the presence of breast abnormality. With the generated ground-truth images, we compared the results of six state-of-the-art image segmentation methods using five supervised evaluation metrics to identify the proficient segmentation methods for hotspot extraction. Based on the evaluation results, the fractional-order Darwinian particle swarm optimization, region growing, mean shift, and fuzzy c-means clustering are found to be more efficient in comparison to k-means clustering and threshold-based segmentation methods.

Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model.

Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 µg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro-computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats.

Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3) p/s/cm(2) /sr (Group A) and 1.11 × 10(4) p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016.

Dioxin Exposure Impairs BMP-2-Mediated Spinal Fusion in a Rat Arthrodesis Model.

BACKGROUND: Cigarette smoking inhibits bone-healing and leads to increased rates of pseudarthrosis. However, the mechanisms behind these effects are controversial. Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin)--a cigarette smoke constituent and potent activator of the aryl hydrocarbon receptor (Ahr)--negatively impacts bone quality and osteoblast differentiation. We hypothesized that activation of the Ahr by dioxin would inhibit bone morphogenetic protein (BMP)-2-mediated spinal fusion in a rat arthrodesis model. METHODS: Female Long-Evans rats were pretreated with dioxin or vehicle in six weekly doses, followed by bilateral posterior lumbar spinal fusion across the L4-L5 transverse processes using recombinant human BMP (rhBMP)-2. Treatments continued until sacrifice at four weeks postoperatively. A third group was treated with dioxin for six weeks, followed by a recovery period of four elimination half-lives to assess the reversible effects of dioxin exposure on spinal fusion capacity. Bone formation and fusion capacity were evaluated using fusion scoring, radiography, micro-computed tomography, and histologic analysis. RESULTS: Fusion scores for dioxin-treated and dioxin-recovery rats were significantly lower than those for controls. Although fusion rates were also significantly reduced in dioxin-treated animals relative to controls (50% versus 100%, respectively), rates were not significantly reduced in dioxin-recovery animals (80%). CONCLUSIONS: Dioxin treatment significantly inhibited spinal fusion in a rat arthrodesis model, and a prolonged cessation of dioxin exposure facilitated only a partial recovery of bone-healing capacity. This finding indicates that, although the effects of dioxin are persistent, an extended recovery from exposure could potentially restore bone regeneration in vivo. CLINICAL RELEVANCE: Development of a pharmacologic agent that reduces the adverse effects of cigarette smoke on bone-healing could prove useful to orthopaedic surgeons. Since dioxin and other similar cigarette smoke toxins exert their effects through Ahr pathway activation, the receptor represents a potential therapeutic target to improve spinal fusion rates in patients who smoke.