International experiences in multicriteria decision analysis (MCDA) for evaluating orphan drugs: a scoping review.

Introduction: Orphan diseases are low-prevalence conditions with chronically debilitating or life-threatening consequences. Their treatments are generally called orphan drugs (OD). Health-technology assessment processes have traditionally considered cost-effectiveness analysis (CEA), when making reimbursement and pricing decisions for health-care plans. Valuing OD with standard CEA raises important issues due to uncertain evidence, inability to meet cost-effectiveness thresholds for reimbursement and high budget impact, among others. Multi-criteria decision analysis (MCDA) allows to overcome these issues and improve the technical and ethical quality of decisions regarding prioritization, coverage, and reimbursement of OD. Areas covered: A scoping review was conducted in order to characterize MCDA frameworks for assessing OD and implementation experiences. We reviewed electronic databases (Medline, Embase, Cochrane Library, EBSCO, CINAHL, EconLit, Web of Science, LILACS, Google Scholar) key journals (Orphanet Journal of Rare Diseases and Value in Health) and organization repositories. Expert opinion: The theoretical framework for MCDA considers areas related to characteristics of orphan diseases and their technologies' clinical and economic impact. Participation processes are critical in incorporating societal values in weighting different dimensions and constructing decision rules. Local implementation pilots considering different stakeholders are necessary in order to pinpoint specific barriers and opportunities.

Assessment of the stability of exogenous gamma hydroxybutyric acid (GHB) in stored blood and urine specimens.

OBJECTIVE: The aim of this work is to test the stability of exogenous GHB in whole blood and urine samples collected from living and deceased GHB free-users, spiked with known concentrations of GHB and stored at different temperatures (-20°C, 4°C and 20°C) up to 4 weeks. MATERIALS AND METHODS: GHB was added to GHB-free ante-mortem blood and urine samples at the concentration of 5 and 10 mg/L, respectively whereas in post-mortem blood and urine specimens at 50 and 10 mg/L respectively. All samples were stored at three different temperatures: -20°C, 4°C and 20°C and extracted and analyzed at three days, 1 week, 2 weeks, 3 and 4 weeks in duplicate. No preservatives were added. GHB was quantified by GC-MS after LLE according to a previously published method. RESULTS: Post-mortem blood specimens showed a reduction of GHB levels higher than 10% only after a period of 4 weeks of storage for samples kept at +4°C and +20°C, whereas samples stored at -20°C showed a mean reduction of 8.7%. In post-mortem urine samples, there was a mean reduction of GHB levels higher than 20% at all storage temperatures, after 4 weeks of storage. Ante-mortem blood samples showed a reduction of GHB levels lower than 10% only after 3 days of storage at -20°C and at +4°C (samples stored at +20°C showed a mean reduction of 10.4%). After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 20% at all storage temperatures. Ante-mortem urine samples showed a reduction of GHB levels higher than 10% after just 3 days of storage for samples kept at all tested temperatures. After 4 weeks of storage, there was a mean reduction of GHB concentrations higher than 25% at all storage temperatures. CONCLUSIONS: According to our findings, it would be useful to perform GHB analysis both in blood and urine specimens within 3 days of sampling and the specimens should be stored at -20°C or 4°C in order to avoid instability issues.

Results of the validation study of the Psodisk instrument, and determination of the cut-off scores for varying degrees of impairment.

BACKGROUND: The Psodisk is a 10-item visual instrument, aimed at measuring the burden of psoriasis on patients. OBJECTIVES: To validate the Psodisk in a large sample of patients with psoriasis, and to define categories for the interpretation of the scores. METHODS: Data were collected in 21 dermatological centres. The Psodisk was administered at baseline (t0), after 2 or 3 days (t1) and about 3 months (t2) after baseline, and data were used to assess validity and reliability of the instrument. The cut-off scores were determined using the perception of the severity of the disease by the patient as anchor point. RESULTS: The evaluable population consisted of 320 patients at baseline, with a mean Psodisk score of 36.9. The concurrent validity of the instrument was confirmed by the high correlation with Skindex-29 and DLQI. Factor analyses selected a single factor, which alone explained almost 60% of the variance. Cronbach's coefficient alpha was 0.927, suggesting a good reliability. Test-retest reliability was verified by a Pearson's correlation coefficient between the Psodisk scores at baseline and t1 of 0.924. Five categories of disease burden were defined: 1. minimal (<9); 2. mild (9-15); 3. moderate (16-30); 4. marked (31-50); 5. severe (>50). CONCLUSION: The Psodisk showed good psychometric properties. The definition of the cut-off scores will be useful to evaluate the burden of psoriasis on patients.

Open mini-invasive cholecystectomy in high risk elderly. A review of 121 consecutive procedures.

INTRODUCTION: the report describes the features of a low cost, open mini-invasive procedure for cholecystectomy in a sample of 121 consecutive high risk elderly (ASA score 3 to 5). PATIENTS AND METHODS: the surgery is performed through a 3 - 4 cm right subcostal skin incision. An optimal exposition of the operating field was achieved thanks to an innovative three valve retractor. RESULTS: a mean hospital stay of 3,02 days, low complication rate and 2,4% mortality are the results of the described procedure. CONCLUSIONS: in high risk elderly the results are extremely encouraging, particularly in comparison with both laparoscopic and traditional open cholecystectomy. The open minisurgical cholecystectomy could be considered a cost-effective alternative to laparoscopy, with excellent results in this subset of patients. The described mini-surgical procedure can also integrate the laparoscopic in case of conversion.

[Epidemiology and epidemiologists: a survey on the presence, structure and training of epidemiologists and medical statisticians in the Veneto region]. / Epidemiologia ed epidemiologi: indagine sulla presenza, or- ganizzazione e formazione di epidemiologi e statistici medici nella Regione Veneto.

The present study aims at assessing the role of epidemiology on health decision-making processes in the public administrations of the Veneto region, north-eastern Italy. In 2003 a questionnaire was mailed to chief-executives of local public health organizations (21 Local Health Units, 2 Public Hospitals), and 18 responded. All public health organizations were practicing Epidemiology, but only 4 had dedicated services. Sixty-two people were working as epidemiologists in public health, but only half played the role for most of their Full Time Employment. Personal educational qualifications were mainly degree in Medicine (62%) and Statistical Sciences (23%). Among physicians, 78% was specialized in Hygiene and Preventive Medicine. The head office of most public health organizations (15 out of 18) appraised epidemiology as fundamental with regard to the health decision-making process, however two thirds of them reported that the epidemiological informative needs were only little or not at all satisfied. To improve the situation, most Public Health Organizations intended to perform educational activities and to use external advisors. In conclusion, Public Health Organizations of the Veneto region appreciated the importance of epidemiology in the health decision-making process. However, few resources were devoted to this field so that informative needs were only partly satisfied.

Informed consent in high-risk renal transplant recipients.

Before performing a clinical, diagnostic, and/or therapeutic action, the doctor is required to provide the patient with a bulk of information defined as informed consent. This expression was used for the first time in 1957 during a court case in California and the two words--informed and consent--are used together to underline the fact that the patient cannot give his or her true consent without first receiving correct information concerning the medical act in question. With regard to the medicolegal aspects governing organ transplants, despite the bulk of detailed work performed by health service workers involved in this surgical field with the aim of preparing adequate informed consent models, this has not yet been accompanied by the necessary legislative development. The informed consent model to be presented to the kidney transplant candidate should include a detailed description of the recipient's comorbidity and should aim at reducing the number of medicolegal actions, which have become more and more frequent in the last few years due to the ever increasing number of patients considered as suitable for transplantation. Informed consent, therefore, should not be a mere bureaucratic formality to be obtained casually, but should be carefully stipulated together with the patient by the transplant surgeon. It is, in fact, an indispensable condition for transforming a potentially illegal action, that is, the violation of an individual's psychophysical integrity, into a legal one.

Clinical assessment of renal vascular involvement and clinical-pathological correlations.

The renal vascular involvement of systemic diseases can be of embolic, thrombotic or inflammatory nature. Occlusion of proximal arterial vessels results in a dissociation between the rapid progression of renal failure, and the urinary abnormalities. Urine examination can be nearly normal and non revealing, except for a loss in maximal concentrating ability. In contrast, inflammatory changes of distal vessels are variably transmitted to the glomeruli, resulting in proteinuria, variable hematuria associated to mixed abnormalities of the urinary sediment. In diffuse vascular involvement acute renal failure can supervene, difficult to distinguish from that of diffuse glomerulonephritides. Most systemic vasculitides, mainly those of SLE, microscopic polyangiitis, Henoch-Schoenlein purpura and that of Wegener granulomatosis cause a clinical picture either of acute, rapidly progressive glomerulonephritis, or of a nephritic syndrome. The vasculitides affecting small arteries, capillaries and venules can result in a clinical-histopathologic picture closely mimicking that of acute tubule-interstitial disease. A thorough evaluation of the clinical picture, of the degree and progression of renal failure, of urine analysis, and clinically guided biopsies of the appropriate tissues can lead to differentiation of the different diseases and precocious diagnosis and effective treatment.

Intrarectal ultrasound and computed tomography in the pre- and postoperative assessment of patients with rectal cancer.

The ability of intrarectal ultrasound to recognize the local extent of disease was investigated in 23 patients with histologically proven adenocarcinoma of the lower two-thirds of the rectum before operation. Two probes, 12 cm long, working at a frequency of 3.5 and 7.5 MHz, were used. The results were compared with those of pre-operative computed tomography (CT) and with the pathological report of the resected specimens. Sonography correctly staged 20 of 23 tumours with two false negatives and one false positive, while CT correctly staged 19 of 23 tumours with two false negatives and two false positives. The results of ultrasound were found to be as accurate as those of CT; the low cost and simple use of ultrasound makes it preferable in the pre-operative assessment of the depth of invasion of rectal cancer. In addition, intrarectal ultrasound was routinely performed in 42 patients, operated on for rectal cancer by means of sphincter-saving procedures, at variable intervals in the first 2 years postoperatively. Eight local recurrences were recognized and confirmed by CT. Based on the low cost, reliability and simple use, intrarectal ultrasound is proposed as first examination for local recurrence detection in the follow-up of patients with low anterior resection for rectal cancer.