Scientific Evidence in Health Technology Assessment Reports: An In-Depth Analysis of European Assessments on High-Risk Medical Devices

Background

The aim of this study was to examine the scientific evidence on clinical effectiveness and safety used in health technology assessments (HTAs) of high-risk medical devices (MDs) in Europe.

Solitary fibrous tumor of the liver expressing CD34 and vimentin： A case report

A case of a successfully treated solitary fibrous tumor （SFT） of the liver is reported. An 82-year-old female presented with left upper abdominal discomfort, a firm mass on palpation, and imaging studies revealed a large tumor, 15 cm in diameter, arising from the left lobe of the liver. A formal left hepatectomy was performed. Microscopic evaluation showed spindle and fibroblast-like cells within the collagenous stroma. Immunohistochemistry disclosed diffuse CD34 and positive vimentin, supporting the diagnosis of a benign SFT. The patient remained well 21 months after surgery. SFT of the liver is a very rare neoplasm of mesenchymal origin. In most cases it is a benign lesion, although some may have malignant histological features and recur locally or metastasize. With less than 30 reported cases in the literature, little can be said regarding its natural history or the benefitsof adjuvant radiochemotherapy. Complete surgical resection remains the cornerstone of its treatment.     

Prospective, observational study of voriconazole therapeutic drug monitoring among lung transplant recipients receiving prophylaxis: factors impacting levels of and associations between serum troughs, efficacy, and toxicity

Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients (n = 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs (n = 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 μg/ml, respectively. The age of the patient directly correlated with initial troughs (P = 0.005). Patients that were ≥ 60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients, ≥ 2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were ≤ 1.5 μg/ml or >1.5 μg/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml (P = 0.07). Invasive fungal infections or colonization were more likely with troughs of ≤ 1.5 μg/ml (P = 0.01) and among patients with no trough of >1.5 μg/ml (P = 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (P = 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of >1.5 μg/ml. A cutoff for toxicity was not identified, but troughs of >4 μg/ml were rare. The data support a target range of >1.5 to 4 μg/ml.     

Discordance between echocardiographic and MRI findings in two cases of acute myocarditis mimicking myocardial infarction

Spontaneous coronary artery dissection (SCAD) still is a rare cause of acute coronary syndrome. SCAD has been observed in three groups of patients: those with coronary atherosclerosis, peripartal women and idiopathic group. SCAD may be associated with some conditions. We report an unusual association: SCAD and pulmonary thromboembolism.     

Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C

OBJECTIVES: Hepatic steatosis is a common feature of chronic hepatitis C. The purpose of this study was to determine factors related to the presence of steatosis and to define the role of steatosis in the response to antiviral treatment in chronic hepatitis C patients. METHODS: We retrospectively analysed all patients with chronic hepatitis C treated in a 5 year period in our department. Patients were included in the study only if a pretreatment liver biopsy specimen was available for evaluation. All patients treated either with interferon in combination with ribavirin, or with pegylated interferon in combination with ribavirin were included irrespectively of their response (early, end of treatment and/or sustained) to antiviral therapy. RESULTS: A total of 116 patients with chronic hepatitis C were included in the study with a mean age of 45.5 +/- 14.1 years. Steatosis was present in 52 patients (44.8%). On univariate analysis age, P = 0.04 and body mass index > or = 25, P = 0.004 were correlated with the presence of steatosis and on multivariate analysis only body mass index > or = 25, P = 0.032. Advanced fibrosis was not found associated with steatosis. Sixty patients out of 116 (51.7%) had sustained virological response (SVR). In particular 42 out of 64 patients with no steatosis (65.6%) had SVR compared to 20 out of 52 patients (38.4%) with any degree of steatosis (P = 0.009). Patients with genotype 2 or 3 had a more favourable outcome compared to patients with 1 or 4 genotypes, 63.2% vs 49.2%, P = 0.032. Also increased age (P = 0.0001), gamma glutamyltransferase (GGT) (P = 0.029), no history of intravenous drugs use (P = 0.001) and advanced fibrosis on pretreatment biopsy (P = 0.046) were correlated with treatment failure. On multivariate analysis significant independent association with SVR was found with the presence of steatosis on pretreatment biopsy (P = 0.004), increased GGT (P = 0.005) and genotype (P = 0.017). CONCLUSION: Steatosis in the liver biopsy performed before the beginning of antiviral treatment was found to be associated only to the body mass index of the patients and to be a strong independent factor for treatment failure.     

Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy: a clinicopathologic study.

BACKGROUND: This study investigates the correlation of hepatic progenitor cells (HPC) expression with treatment response in patients with chronic hepatitis C. DESIGN: The study comprised 77 liver biopsies with chronic hepatitis C (HCV). All patients were PCR-HCV (+) and received antiviral therapy with interferon or pegylated interferon alpha-2b and ribavirin. Twenty-nine patients were assigned as responders (group A), 29 as nonresponders (group B) and 19 as relapsers (group C). Ten normal liver biopsies were used as controls. Liver paraffin sections were subjected (a) to immunohistochemistry using antibodies for cytokeratins 19 (CK19) and 7 (CK7), alpha-fetoprotein (AFP), leukocyte common antigen (LCA) and CD34 antigen (b) to in situ hybridization for AFP mRNA and (c) to immunohistochemistry+in situ hybridization. Results were expressed as % of positive cells following morphometric analysis. RESULTS: HPC expression was present in all 87 specimens. In the control biopsies, rare HPC were detected. In the CH cases and according to AFP mRNA expression, the grade for % HPC expression was: group B: 53.2+/-2.6> group C: 48.37+/-1.8> group A: 31.4+/-1.6 (group A vs B P<0.01, group A vs C P<0.01, group B vs C P>0.05. Double stain revealed that HPC coexpressed CK19/AFP mRNA, CK7/AFP mRNa and AFP protein/AFP mRNA. HPC-percentages were directly correlated with total HAI score (P<0.01), fibrosis stage (P<0.01), and transaminase values (P<0.05). CONCLUSIONS: This study demonstrates that in cases of chronic hepatitis C, the significant association of HPC expression with the severity of disease and more specifically with the response to treatment implies that HPC development and proliferation may provide additional prognostic information and predict prognosis in such cases.     

Whole-blood interferon-gamma assay for the diagnosis of tuberculosis infection in an unselected Greek population

Background and objective:   Although QuantiFERON-TB Gold (QFT-G) has been approved for the diagnosis of latent tuberculosis infection (LTBI), there are limited data regarding its performance in routine clinical practice. The aim of this study was to compare QFT-G 'In Tube' results, based on stimulation with Mycobacterium tuberculosis- specific antigens, with tuberculin skin test (TST) results in an unselected hospital-based Greek population.
Methods:   This was a prospective study of inpatients and outpatients in the University Hospital of Larissa, Greece. Demographic, clinical and microbiological data were collected and correlated to the QFT-G 'In Tube' results. Agreement was tested using the Q -test; kappa coefficient and confounding factors were adjusted for by univariate and multivariable logistic regression.
Results:   Among the 191 patients with valid results for both tests, the concordance between the TST and the QFT-G was 68.5%, with a kappa value of 0.38 (95% CI 0.2–0.5). In 27 (14.1%) patients with active tuberculosis, QFT-G 'In Tube' yielded 85.1% positive results compared with 74% for the TST ( P  = 0.45).
Conclusions:   Overall agreement between the QFT-G 'In Tube' assay and the TST in this unselected hospital population was low, mainly due to discordant TST-positive/QFT-negative results.     

Short progression-free survival predicts for poor overall survival in older patients with multiple myeloma treated upfront with novel agent-based therapy

Objectives: To assess the importance of the quality of response and of early relapse in unselected elderly patients with myeloma treated upfront with novel agents. Methods: We analyzed 135 unselected transplant‐ineligible patients older than 65 yr who were treated upfront with novel agent‐based regimens in a single center. Results: On intent to treat, 81% of patients achieved a response (28% sCR/CR, 23% VGPR, and 30% PR). Median progression‐free survival (PFS) for patients who achieved sCR/CR was 31 vs. 20 months for VGPR and 23 months for PR (P = 0.048). Median overall survival (OS) for patients with sCR/CR was 62 months, 53 months for VGPR and 38 months for patients with PR (P = 0.028). Early relapse (PFS < 12 months) was more common in patients with PR (39% vs. 21% for VGPR vs. 3% for sCR/CR). Patients who relapsed or progressed <12 months from initiation of treatment had a median OS of 15.4 months compared with 53 months (P < 0.001) for patients who had a PFS > 12 months despite the fact that after relapse or progression most patients were treated again with novel agents. In multivariate analysis, short PFS was the most significant adverse prognostic factor affecting OS, associated with a 7.25‐fold (P < 0.0001) increase in the risk of death. Conclusion: In newly diagnosed patients over 65 yr, treated upfront with novel agents achievement of CR and a PFS ≥12 months is associated with improved outcome. Patients who fail to respond or experience early relapse after primary therapy with novel agent‐based regimens should be encouraged to participate in clinical trials of novel agents and combinations.     

Conservative surgical treatment of medication related osteonecrosis of the jaw (MRONJ) lesions in patients affected by osteoporosis exposed to oral bisphosphonates: 24 months follow-up

The purpose of the study was to evaluate the efficacy of conservative surgical treatment of medication related osteonecrosis of the jaw (MRONJ) in patients affected by osteoporosis and exposed to oral bisphosphonates (BPs).Subjects diagnosed with MRONJ and osteoporosis under oral BPs that had undergone conservative surgery and had at least 24 months follow-up were included. All patients received medical-antibiotic therapy and then underwent conservative surgical treatment consisting of sequestrectomy, soft tissue debridement and bone curettage with limited or no extension.A total of 53 patients, mean age of 71.9 ± 10.2 years (range 41–87), were enrolled. Two years after conservative surgical therapy 45 patients (91.8%) showed complete healing. The presence of rheumatoid arthritis (p = 0.003) and a more severe initial MRONJ stage (p = 0.023) were associated with a negative surgical outcome while the presence of bone sequestrum was strongly associated with a positive outcome (p = 0.036).Conservative surgical treatment of MRONJ lesions in patients affected by osteoporosis and receiving only oral BPs may represent a valid therapeutic approach determining a high number of complete healing cases. Conservative surgery should be encouraged at early MRONJ stages and after medical therapy failure.