To what extent are current guidelines for cutaneous melanoma follow up based on scientific evidence?

BACKGROUND: Clinical practice guidelines should aim to assist clinicians in making evidence-based choices in the care of their patients. This review attempts to determine the extent of evidence-based support for clinical practice guideline recommendations concerning cutaneous melanoma follow up and to evaluate the methodological quality of these guidelines. METHODS: Current guidelines providing graded recommendations regarding patient follow up were identified through a systematic literature review. The authors reviewed the evidence base used to formulate recommendations in each of the guidelines and appraised the quality of the guidelines using the AGREE II (Appraisal of Guidelines for Research and Evaluation) instrument. RESULTS: Most guideline recommendations concerning the frequency of routine skin examinations by a clinician and the use of imaging and diagnostic tests in the follow up of melanoma patients were based on low-level evidence or consensus expert opinion. Melanoma follow-up guidelines are of variable methodological quality, with some guidelines not recommended by the appraisers for use in clinical practice. CONCLUSION: Clinicians should be aware of how scant the evidence base is for many recommended courses of action. As a consequence of the paucity of evidence in the field of melanoma follow up, there is considerable variability in the guidance provided. The variable methodological quality of guidelines for melanoma follow up could be improved by attention to the criteria described in AGREE II.

Motor evoked potentials and disability in secondary progressive multiple sclerosis.

BACKGROUND: To investigate the mechanisms underlying disability in multiple sclerosis (MS), 40 patients with the relapsing-remitting form of the disease and 13 patients with secondary progressive MS underwent multimodal evoked potential (EP), motor evoked potential (MEP), and spinal motor conduction time evaluation. Clinical disability was evaluated by the expanded disability status scale (EDSS) and functional system scales. In secondary progressive MS patients, magnetic resonance imaging (MRI) was used to obtain a semiquantitATive estimate of the total lesion load of the brain. RESULTS: Spinal motor conduction time was significantly longer in secondary progressive MS patients than controls (p < 0.001) and relapsing-remitting MS patients (p < 0.05), but did not differ between relapsing-remitting patients and controls. Spinal motor conduction times also correlated directly with EDSS scores (p < 0.001) and pyramidal functional system scores (p < 0.001). Brain lesion load (4960.3 +/- 3719.0 mm2) and the total number of lesions (67.7 +/- 37.0) in secondary progressive MS did not correlate with disability scores. For the following EPs, the frequencies of abnormalities were significantly higher in secondary progressive MS patients than relapsing-remitting patients: visual evoked potentials (p < 0.05), somatosensory evoked potentials and upper limb motor evoked potentials (p < 0.01), and brainstem auditory evoked potentials, lower limb somatosensory evoked potentials and lower limb motor evoked potentials (p < 0.001). CONCLUSIONS: These findings suggest that disability in secondary progressive MS patients is mainly due to progressive involvement of corticospinal tract in the spinal cord.

The effect of imprecise repositioning on lesion volume measurements in patients with multiple sclerosis.

In this study, we evaluated the effect of imprecision in patient repositioning encountered in real life on multiple sclerosis (MS) lesion volumes measured from MRIs. We also evaluated two putative methods for reducing the variability in these lesion volume measurements: first, a reduction of slice thickness (from the conventional 5 mm to 3 mm) and second, the application of a new repositioning technique based on the use of head immobilization shells. We evaluated the errors in lesion volume by scanning 10 patients a total of four times using the two slice thicknesses and two repositioning methods (conventional and using a head immobilization shell). The mean absolute percentage difference between two corresponding scans was 6.8% (range, 1.24 to 11%) using conventional slice thickness and repositioning, 4.1% (range, 0.7 to 5.56%) using conventional slice thickness and head immobilization shells, 2.6% (range, 0.8 to 6.66%) using the conventional repositioning technique and 3-mm slice thickness, and 1.4% (range, 0.2 to 6.14%) using slice thickness of 3 mm and head immobilization shells. These mean absolute differences were significantly different (p = 0.0008). Our results indicate that the effect of repositioning errors of the order of those that can be encountered in the daily life situation of clinical trials affects significantly lesion load measurements in MS and that the combined use of thinner slices and more accurate repositioning techniques can markedly improve the reproducibility of such measurements.

Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.

OBJECTIVES: To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS: T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS: Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS: More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous.

Two sisters with multiple sclerosis, lamellar ichthyosis, beta thalassaemia minor and a deficiency of factor VIII.

Two of four sisters have multiple sclerosis (MS), lamellar ichthyosis, beta thalassaemia minor and a quantitative deficit of factor VIII-von Willebrand complex. The mother and the other sisters have only beta thalassaemia minor. The association of MS and a cluster of genetically determined diseases is rare. Such families could offer a new approach to the investigation of the polygenetic background of MS.

Immunological and gadolinium-DTPA MRI evaluation of relapsing remitting multiple sclerosis.

The levels of lymphocytes, blood lymphocytes subsets (CD3+, CD4+, CD8+, DR+, CD25+, CD4+, CD45RA+, CD4+, CD29+ cells) and sIL-2r of 10 patients affected by relapsing-remitting multiple sclerosis were serially studied. The identification of the activity of the disease was made by gadolinium-DTPA (Gd-DTPA) MRI. The immunological determinations and the MRI of the brain and spinal cord were performed every 14th day for a period of three months. No significant difference of the immunological values were found between the presence and the absence of Gd-DTPA enhancing areas, except lymphocytes (p < 0.05). These immunological parameters, evaluated in the peripheral blood, are not a marker of disease activity in relapsing-remitting MS patients.

Gadolinium-pentetic acid magnetic resonance imaging in patients with relapsing remitting multiple sclerosis.

Ten patients with relapsing-remitting multiple sclerosis have been studied by serial gadolinium-pentetic acid magnetic resonance imaging (MRI) every 14 days for 3 months. At the end of the follow-up, seven relapses occurred in six patients; no therapy was administered during the study. Ninety-three enhancing lesions were collected in eight patients. With regard to the duration of the enhancement, 32 lesions were detected in only one MRI scan and 32 were found in more MRI scans (most of the lesions occurring in two serial examinations). Four old lesions increased their size with delayed enhancement. Correlation was found between the relapses and the gadolinium-pentetic acid-enhancing areas only for one brain-stem and two cervical spinal cord lesions. Gadolinium-pentetic acid MRI provides useful information about activity of the disease that cannot be obtained clinically even if the dynamic of the lesions may be undervalued in old plaques.

Total lymphoid irradiation in chronic progressive multiple sclerosis.

6 patients with severe chronic progressive multiple sclerosis were subjected to total lymphoid irradiation (TLI) to assess clinical efficacy and side effects. During a 4 year follow-up the disability progression was continuous. Side effects during TLI were well tolerated; side effects after TLI brought about a worsening of the quality of life. One patient died of pneumonia. In this preliminary study TLI did not reduce the worsening of disability in MS patients.

Cerebral hemorrhage and thrombotic thrombocytopenic purpura during ticlopidine treatment: case report.

We report the second case of thrombotic thrombocytopenic purpura occurring during ticlopidine therapy. A cerebral hemorrhage was the first sign of the thrombocytopenia. Even if thrombocytopenia is a rare occurrence with ticlopidine therapy, we stress that platelets must be repeatedly monitored.

[Progressive multiple sclerosis. Evaluation of the effectiveness of total lymph node irradiation]. / Sclerosi multipla progressiva. Valutazione dell'efficacia dell'irradiazione linfonodale totale.

A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Instituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable.