Medical and financial burden of acute intermittent porphyria

Introduction: A small proportion of patients with acute intermittent porphyria (AIP) suffer from recurrent porphyric attacks, with a severely diminished quality of life. In this retrospective case-control study, the burden of disease is quantified and compared among three AIP patient subgroups: cases with recurrent attacks, cases with one or occasional attacks and asymptomatic carriers. Methods: Data from patient records and questionnaires were collected in patients between 1960 and 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. We collected symptoms related to porphyria, porphyria related complications, attack frequency, hospitalisation frequency, hospitalisation days related to acute porphyric attacks, frequency of heme infusions and medical healthcare costs based on hospitalisations and heme therapy. Results: In total 11 recurrent AIP cases, 24 symptomatic AIP cases and 53 AIP carriers as controls were included. All recurrent patients reported porphyria related symptoms, such as pain, neurological and/or psychiatric disorders, and nearly all developed complications, such as hypertension and chronic kidney disease. In the recurrent cases group, the median lifelong number of hospitalisation days related to porphyric attacks was 82 days per patient (range 10–374), and they spent a median of 346 days (range 34–945) at a day-care facility for prophylactic heme therapy; total follow-up time was 243 person-years (PYRS). In the symptomatic non-recurrent group the median lifelong number of hospitalisation days related to porphyric attacks was 7 days per patient (range 1–78), total follow-up time was 528 PYRS. The calculated total medical healthcare cost for recurrent cases group was €5.8 million versus €0.3 million for the symptomatic cases group

How to perform a comprehensive search for FDG-PET literature

In this study, a comprehensive, unbiassed search strategy for identifying literature on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in Medline, Embase and Current Contents was developed, with specific search strategies for each database, using MeSH terms as well as free text words for PET and FDG. To examine which text words apply to FDG, we evaluated the ways of spelling FDG in a random sample of FDG-PET articles (n = 100). These words were used as free text words in the two databases and overlap was determined. PET publications were identified using the text words "positron emission tomography" and "pet$" combined with the respective MeSH terms for each database. To compare the yield of the combined FDG-PET strategy in each database, the retrieved citations were downloaded to Pro-Cite 4.0. Finally, we added search terms for lung cancer, breast cancer, melanoma, head and neck cancer and lymphoma to our strategy and to a short strategy (consisting of the text words "positron emission tomography" and "fdg"). In order to measure the yield and precision (positive predictive value, PPV) of our search strategy and compare it with the short one, we screened the title and abstract of the retrieved citations. Reviewing a random sample of the FDG-PET literature yielded 56 different ways of spelling FDG. We confined the list to 11 text words, without missing articles. Of the publications retrieved by these text words, only 4% were indexed by the MeSH term "Fludeoxyglucose F18" in Medline and 29% by the MeSH-term "Fluorodeoxyglucose F18" in Embase. Only 51% of PET articles were indexed by the MeSH term "Tomography, emission-computed" in Medline and 40% by the MeSH term "Positron emission tomography" in Embase. The combined search strategy for identifying studies on FDG and PET resulted in 2865 publications in Medline and 2646 in Embase. Medline identified 1662 publications not found by Embase; Embase identified 1422 publications not found by Medline. Compared with the short strategy, our search strategy yielded on average 52% more publications (94%, 41% and 20% more in Medline, Embase and Current Contents, respectively). The PPV of our strategy (percent of publications that were really on PET, FDG and the specified subject) was 70%, compared with 76% using the short strategy. Regardless of the strategy used, Embase yielded more publications and was also slightly more specific than Medline. With the recommended strategy, FDG-PET publications can be identified more efficiently. We have shown the importance of searching more than one database and emphasize the use of both MeSH terms and text words in a search strategy. Standardization of the spelling of FDG and indexing of articles on FDG would substantially simplify searchin

Rapid evaluation of FDG imaging alternatives using head-to-head comparisons of full ring and gamma camera based PET scanners - a systematic review

Aim: While FDG full ring PET (FRPET) has been gradually accepted in oncology, the role of the cheaper gamma camera based alternatives (GCPET) is less clear. Since technology is evolving rapidly, "tracker trials" would be most helpful to provide a first approximation of the relative merits of these alternatives. As difference in scanner sensitivity is the key variable, head-to-head comparison with FRPET is an attractive study design. This systematic review summarises such studies. Methods: Nine studies were identified until July 1, 2000. Two observers assessed the methodological quality (Cochrane criteria), and extracted data. Results: The studies comprised a variety of tumours and indications. The reported GC- and FRPET agreement for detection of malignant lesions ranged from 55 to 100%, but with methodological limitations (blinding, standardisation, limited patient spectrum). Mean lesion diameter was 2.9 cm (SD 1.8), with only about 20% <1.5 cm. The 3 studies with the highest quality reported concordances of 74-79%, for the studied lesion spectrum. Contrast at GCPET was lower than that of FRPET, contrast and detection agreement were positively related. Logistic regression analysis suggested that pre-test indicators might be used to predict FRPET-GCPET concordance. Conclusion: In spite of methodological limitations, "first generation" GCPET devices detected sufficient FRPET positive lesions to allow prospective evaluation in clinical situations where the impact of FRPET is not confined to detection of small lesions (<1.5 cm). The efficiency of head-to-head comparative studies would benefit from application in a clinically relevant patient spectrum, with proper blinding and standardisation of acquisition procedures

Health-related quality of life following FDG-PET/CT for cytological indeterminate thyroid nodules

Objective: This study assessed the health-related quality of life (HRQoL) in patients undergoing 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT for an indeterminate (Bethesda III/IV) thyroid nodule. FDG-PET/CT accurately rules out malignancy and prevents 40% of futile diagnostic surgeries in these nodules.Design: Secondary analyses of HRQoL data from a randomised controlled multicentre trial (NCT02208544) in 126 patients from 15 hospitals in the Netherlands were done.Methods: Longitudinal HRQoL assessment was performed using the EuroQol 5-dimension 5-level (EQ-5D-5L), the RAND 36-item Health Survey v2.0 (RAND-36), and the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire on baseline, 3, 6, and 12 months, relative to the date of the FOG-PET/CT scan.Results: Patients who were randomised to active surveillance following an FDG-negative nodule instead of diagnostic surgery reported stable HRQoL scores throughout the year. Univariate analysis indicated better HRQoL for patients undergoing surveillance than surgical patients with benign histopathology on multiple physical and psychosocial domains. Univariate within-group analysis suggested both temporary and continued HRQoL deteriorations in patients with benign histopathology over time. Multivariate within-group analysis demonstrated no significant longitudinal HRQoL changes in patients undergoing active surveillance. In contrast, in patients with benign histopathology, worse HRQoL was observed with regard to ThyPRO cognitive impairment (P = 0.01) and cosmetic complaints (P = 0.02), whereas goitre symptoms (P < 0.001) and anxiety (P = 0.04) improved over time. In patients with malignant histopathology, anxiety also decreased (P = 0.05).Conclusions: The reassurance of a negative FDG-PET/CT resulted in sustained HRQoL throughout the first year of active surveillance. Diagnostic surgery for a nodule with benign histopathology resulted in more cognitive impairment and physical problems including cosmetic complaints, but improved goitre symptoms and anxiety. Anxiety was also reduced in patients with malignant histopathology.Metabolic health: pathophysiological trajectories and therap