Dedicated teams to optimize quality and safety of surgery: A systematic review.

BACKGROUND: A dedicated operating team is defined as a surgical team consisting of the same group of people working together over time, optimally attuned in both technical and/or communicative aspects. This can be achieved through technical and/or communicative training in a team setting. A dedicated surgical team may contribute to the optimization of healthcare quality and patient safety within the perioperative period. METHOD: A systematic review was conducted to evaluate the effects of a dedicated surgical team on clinical and performance outcomes. MEDLINE and Embase were searched on 23 June 2022. Both randomized controlled trials (RCTs) and non-randomized studies (NRSs) were included. Primary outcomes were mortality, complications and readmissions. Secondary outcomes were costs and performance measures. RESULTS: Fourteen studies were included (RCTs n = 1; NRSs n = 13). Implementation of dedicated operating teams was associated with improvements in mortality, turnover time, teamwork, communication and costs. No significant differences were observed in readmission rates and length of hospital stay. Results regarding duration, glitch counts and complications of surgery were inconclusive. Limitations include study conduct and heterogeneity between studies. CONCLUSIONS: The institution of surgical teams who followed communicative and/or technical training appeared to have beneficial effects on several clinical outcome measures. Dedicated teams provide a feasible way of improving healthcare quality and patient safety. A dose-response effect of team training was reported, but also a relapse rate, suggesting that repetitive training is of major concern to high-quality patient care. Further studies are needed to confirm these findings, due to limited level of evidence in current literature. PROSPERO REGISTRATION NUMBER: CRD42020145288.

Prevention of postoperative delirium in elderly patients planned for elective surgery: systematic review and meta-analysis.

Introduction: Vulnerable or "frail" patients are susceptible to the development of delirium when exposed to triggers such as surgical procedures. Once delirium occurs, interventions have little effect on severity or duration, emphasizing the importance of primary prevention. This review provides an overview of interventions to prevent postoperative delirium in elderly patients undergoing elective surgery. Methods: A literature search was conducted in March 2018. Randomized controlled trials (RCTs) and before-and-after studies on interventions with potential effects on postoperative delirium in elderly surgical patients were included. Acute admission, planned ICU admission, and cardiac patients were excluded. Full texts were reviewed, and quality was assessed by two independent reviewers. Primary outcome was the incidence of delirium. Secondary outcomes were severity and duration of delirium. Pooled risk ratios (RRs) were calculated for incidences of delirium where similar intervention techniques were used. Results: Thirty-one RCTs and four before-and-after studies were included for analysis. In 19 studies, intervention decreased the incidences of postoperative delirium. Severity was reduced in three out of nine studies which reported severity of delirium. Duration was reduced in three out of six studies. Pooled analysis showed a significant reduction in delirium incidence for dexmedetomidine treatment, and bispectral index (BIS)-guided anaesthesia. Based on sensitivity analyses, by leaving out studies with a high risk of bias, multicomponent interventions and antipsychotics can also significantly reduce the incidence of delirium. Conclusion: Multicomponent interventions, the use of antipsychotics, BIS-guidance, and dexmedetomidine treatment can successfully reduce the incidence of postoperative delirium in elderly patients undergoing elective, non-cardiac surgery. However, present studies are heterogeneous, and high-quality studies are scarce. Future studies should add these preventive methods to already existing multimodal and multidisciplinary interventions to tackle as many precipitating factors as possible, starting in the pre-admission period.

Endorsement of ICMJE's Clinical Trial Registration Policy: a survey among journal editors.

BACKGROUND: Since 2005, the International Committee of Medical Journal Editors (ICMJE) requires researchers to prospectively register their clinical trials in a publicly accessible trial registry. The Consolidated Standards of Reporting Trials (CONSORT) statement has supported this policy since 2010. We aimed to evaluate to what extent biomedical journals have incorporated ICMJE's clinical trial registration policy into their editorial and peer review process. METHODS: We searched journals' instructions to authors and performed an internet survey among all journals publishing reports of randomised controlled trials that follow ICMJE's Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals (n = 695), and/or that endorse the CONSORT statement (n = 404) accessed in January 2011. Survey invitations were sent to the email addresses of the editorial offices and/or editors-in-chief of included journals in June 2011. RESULTS: For 757 ICMJE and/or CONSORT journals, we identified that they published RCT reports. We could assess the instructions to authors of 747 of these; 384 (51%) included a statement of requiring trial registration, and 33 (4%) recommended this. We invited 692 editorial offices for our survey; 253 (37%) responded, of which 50% indicated that trial registration was required; 18% cross-checked submitted papers against registered records to identify discrepancies; 67% would consider retrospectively registered studies for publication. Survey responses and specifications in instructions to authors were often discordant. CONCLUSION: At least half of the responding journals did not adhere to ICMJE's trial registration policy. Registration should be further promoted among authors, editors and peer reviewers.

Drug survival is not significantly different between biologics in patients with psoriasis vulgaris: a single-centre database analysis.

BACKGROUND: Drug survival depends on several factors such as dosing, effectiveness, quality-of-life improvement and safety, and could be seen as an overall marker for treatment success. Such data for biologics in psoriasis treatment are sparse. OBJECTIVES: To determine differences in drug survival between different biologics for psoriasis. METHODS: Drug survival, dosing, Psoriasis Area and Severity Index (PASI) and Skindex-29 at weeks 12 and 52, and adverse events of patients with psoriasis treated with a biologic registered in the local database of the Academic Medical Center, Amsterdam, were analysed. Patients were divided into those naive or non-naive for treatment episodes with biologics. RESULTS: Drug survival did not differ significantly for naive treatment episodes between the biologics (etanercept 85% to 64%, adalimumab 77% to 77%, infliximab 75% to 75% for year 1-4), or for non-naive treatment episodes (etanercept 86% to 42%, adalimumab 84% to 56%, infliximab 68% to 43% for year 1-4; ustekinumab 84% to 57% for year 1-3). The naive group showed better drug survival and PASI 75 response at week 12, although the difference was not significant. A similar improvement of mean ∆PASI and mean ∆Skindex-29 was observed at weeks 12 and 52 for all biologics for both groups, although no significant difference was seen between groups. Treatment termination was due mainly to nonresponse for all biologics. CONCLUSIONS: There was no significant difference in drug survival, mean ∆PASI or Skindex-29 response at weeks 12 or 52 between the biologics or between the naive and non-naive groups. Treatment termination was due mostly to nonresponse. Sequential treatment with the available biologics can be effective.

Brodalumab and ixekizumab, anti-interleukin-17-receptor antibodies for psoriasis: a critical appraisal.

AIM: Papp et al. (N Engl J Med 2012; 366: 1181-9) and Leonardi et al. (N Engl J Med 2012; 366: 1190-9) respectively assessed the efficacy and safety of brodalumab (AMG 827), a human monoclonal antibody directed against interleukin (IL)-17RA, the receptor of IL-17A and ixekizumab (LY2439821), a humanized anti-IL-17 monoclonal antibody for the treatment of moderate-to-severe plaque psoriasis. SETTING AND DESIGN: In these phase II, multicentre, randomized, double-blind, placebo-controlled, dose-ranging studies, 198 patients with severe chronic plaque-type psoriasis [Psoriasis Area and Severity Index (PASI) ≥ 12, body surface area (BSA) ≥ 10] were enrolled in Papp et al. between December 2009 and April 2010 and 142 patients in Leonardi et al. between April 2010 and March 2011. STUDY EXPOSURE: In Papp et al., patients with chronic plaque-type psoriasis were randomly assigned to receive placebo or brodalumab at a dose of 70, 140 or 210 mg, administered subcutaneously on day 1 and at weeks 1, 2, 4, 6, 8 and 10, or at a dose of 280 mg administered subcutaneously on day 1 and at weeks 4 and 8. In Leonardi et al., patients were randomly assigned to receive subcutaneous injections of placebo or 10, 25, 75 or 150 mg of ixekizumab at 0, 2, 4, 8, 12 and 16 weeks, followed by a 4-week follow-up period. OUTCOMES: In both studies the PASI, static Physician's Global Assessment (sPGA), Dermatology Life Quality Index (DLQI), adverse events, and routine haematological and laboratory values were analysed. Additionally in Papp et al. the BSA and Medical Outcomes Study 36-item short-form health survey, and in Leonardi et al. the joint pain visual analogue scale (VAS), itch severity VAS, Nail Psoriasis Severity Index (NAPSI) and the Psoriasis Scalp Severity Index (PSSI) were also measured. PRIMARY OUTCOME MEASURES: At week 12, in Papp et al. and Leonardi et al.: (A) The percentage improvement in PASI. In Leonardi et al. (and in Papp et al. as one of the secondary outcomes): (B) The percentage of patients who achieved a reduction in the PASI by at least 75% (PASI 75) over baseline. RESULTS: Primary endpoints: (A) At week 12 in Papp et al., the mean improvements in PASI were significantly greater in the 140, 210 and 280 mg brodalumab groups than in the 70 mg brodalumab group (85.9%, 86.3% and 76.0%, respectively, vs. 45.0%; P < 0.001); in addition, the mean improvement in PASI was significantly greater in each brodalumab group than in the placebo group (16.0%; P < 0.001). (At week 16 lower but still significant percentages compared with placebo were seen). In Leonardi et al., the mean improvements in PASI of the 10, 25, 75 and 150 mg ixekizumab groups are not reported. Significant differences between the two highest dose groups and the placebo group were seen as early as 1 week in PASI. (B) At week 12 in Papp et al., the percentages of patients with PASI 75 were 33% in the 70 mg, 77% in the 140 mg, 82% in the 210 mg and 67% in the 280 mg brodalumab group. The percentages of patients with a 50%, 75%, 90% or 100% improvement in PASI at week 12 were significantly higher among patients who received brodalumab (taking into account all doses) than among patients who received placebo. The authors do not give an explanation for the lower improvements at week 16. In Leonardi et al., the PASI 75 occurred in significantly more patients in the 25 mg (76.7%), 75 mg (82.8%) and 150 mg (82.1%) ixekizumab groups vs. placebo (7.7%; P < 0.001). No significant difference was seen for the 10 mg group. Significant differences between the 150 mg group and the placebo group were seen as early as 2 weeks in PASI 75. Differences were sustained through 20 weeks for all clinical measures in the ixekizumab study. Secondary endpoints: At week 12, in Papp et al., significant decreases of BSA, sPGA and DLQI were also seen. In Leonardi et al., significantly higher percentages of patients in the three highest ixekizumab dose groups had an sPGA score of 0 (clear of disease) or of 0 or 1 (minimal disease) for each dose and score group vs. placebo (P < 0.05). Significant reductions in the mean ± SD DLQI scores were detected at 8 weeks in the 150 mg ixekizumab group (-7.8 ± 5.7), the 75 mg ixekizumab group (-8.5 ± 5.1) and the 25 mg ixekizumab group (-7.1 ± 6.5) as compared with placebo (-2.4 ± 4.4) for all comparisons (P < 0.001). In addition, at 16 weeks, significantly more patients had a DLQI score of 0 in the 150, 75 and 25 mg ixekizumab groups (39.3%, 37.9% and 31.0%, respectively) as compared with placebo (0%) for all comparisons (P < 0.05). In Leonardi et al., significant reductions were seen in the PSSI, in the NAPSI and in the itch severity (VAS scores). Significant reductions from baseline of the joint pain VAS were also observed in the 150 mg ixekizumab group at 12 weeks, and this reduction was sustained through 20 weeks. At week 16: with respect to the other secondary efficacy endpoints and patient-reported outcomes, significant improvements in scores were seen compared with placebo, but some of these differences were lower than observed at week 12. SAFETY: Papp et al. summarized that during the first 12 weeks of the trial, 68% of the patients in the 70 mg brodalumab group, 69% (140 mg), 82% (210 mg), 73% (280 mg) and 62% in the placebo group had at least one adverse event. Although the authors mentioned only three serious adverse events, four were reported during the study: renal colic (70 mg brodalumab group), two patients with grade 3 asymptomatic neutropenia (210 mg brodalumab group; Papp et al. clarified that only one of these episodes was a serious adverse event) and an ectopic pregnancy in one patient in the placebo group. Leonardi et al. reported that there were no serious adverse events in any group. The frequency of adverse events was similar between the combined ixekizumab groups and the placebo group. A few patients were withdrawn from the trial due to adverse events including hypertriglyceridaemia (placebo group), peripheral oedema (10 mg ixekizumab), hypersensitivity (10 mg ixekizumab) and urticaria (25 mg ixekizumab). CONCLUSIONS: Papp et al. and Leonardi et al. concluded that brodalumab and ixekizumab, respectively, significantly improved plaque psoriasis in 12-week, phase II studies. For difficult-to-treat areas such as the scalp and nails, significant differences from placebo were observed with ixekizumab treatment. These trials were not large enough or of long enough duration to ascertain uncommon adverse events or to assess the risk of infection or cardiovascular events.

Systematic reviews and meta-analyses of preclinical studies: publication bias in laboratory animal experiments.

In 2006, Peters et al. identified 86 systematic reviews (SRs) of laboratory animal experiments (LAEs). They found 46 LAE meta-analyses (MAs), often of poor quality. Six of these 46 MAs tried to assess publication bias. Publication bias is the phenomenon of an experiment's results determining its likelihood of publication, often over-representing positive findings. As such, publication bias is the Achilles heel of any SR. Since researchers increasingly become aware of the fact that SRs directly support the 'three Rs', we expect the number of SRs of LAEs will sharply increase. Therefore, it is useful to see how publication bias is dealt with. Our objective was to identify all SRs and MAs of LAEs where the purpose was to inform human health published between July 2005 and 2010 with special attention to MAs' quality features and publication bias. We systematically searched Medline, Embase, Toxline and ScienceDirect from July 2005 to 2010, updating Peters' review. LAEs not directly informing human health or concerning fundamental biology were excluded. We found 2780 references of which 163 met the inclusion criteria: 158 SRs, of which 30 performed an MA, and five MAs without an SR. The number of SRs roughly doubled every three years since 1997. The number of MAs roughly doubled every five years since 1999. Compared with before July 2005, more MAs were preceded by SR and reported on (quality) features of included studies and heterogeneity. A statistically significant proportion of MAs considered publication bias (26/35) and tried to formally assess it (21/35).

[From the Cochrane Library: ultrasonographic screening for abdominal aortic aneurysm in men aged 65 years and older: low risk of fatal aneurysm rupture]. / Uit de Cochrane Library: echografische screening van aorta abdominalis bij mannen van 65 jaar en ouder: kleiner risico op dodelijke aneurysmaruptuur.

Abdominal aortic aneurysm (AAA) is present in 5-10% of men aged 65-79 years and is often asymptomatic. The major complication is rupture, which requires emergency surgery. The mortality rate after rupture is high: about 80% of those who reach the hospital and 50% of those undergoing emergency surgery will die. Elective surgical repair of AAA aims to prevent death from rupture; the 30-day surgical mortality rate for open surgery is approximately 5%. Currently elective surgical repair is recommended for aneurysms larger than 5-5 cm to prevent rupture. There is interest in population screening to detect, monitor and repair AAA before rupture. A Cochrane systematic review of 4 randomised studies involving 127,891 men and 9,342 women revealed a significant reduction in mortality from AAA in men aged 65-79 years who underwent ultrasonographic screening (odds ratio (OR): 0.60; 95% CI: 0.47-0.78). There was insufficient evidence to demonstrate a benefit in women. Men who had been screened underwent more surgery for AAA (OR: 2.03; 95% CI: 1.59-2.59). These findings should be considered carefully when determining whether a coordinated population-based screening programme should be introduced. A gap in the current research is the balance of benefits and risks in women. Furthermore, detailed studies are needed on how to best provide information on the potential benefits and risks to individuals who are offered screening, and on the psychological effects of screening on patients and their partners.

Hexokinase III, cyclin A and galectin-3 are overexpressed in malignant follicular thyroid nodules.

BACKGROUND: Distinguishing malignant thyroid nodules in patients with follicular cytology by fine-needle aspiration (FNA) remains problematic. The large majority of thyroid nodules (> 85%) are overtreated. Therefore, a clear need exists to develop more accurate initial diagnostic tests for follicular thyroid nodules. Galectin-3 is the most recent promising marker to aid discrimination between benign and malignant thyroid lesions; however, this biomarker can be absent in follicular malignancies. AIMS: This study was undertaken to determine whether additional biomarkers can help to discriminate between benign and malignant thyroid nodules. METHODS: Surgical specimens of 36 patients with benign (n = 12) and malignant (n = 24) thyroid nodules showing follicular cytology were assessed by immunohistochemistry for the expression of galectin-3 and novel biomarkers. RESULTS: Expression of hexokinase III (HK III) (P = 0.000) cyclin A (P = 0.002) and galectin-3 (P = 0.003) differed significantly between benign and malignant thyroid nodules. HK III had a sensitivity of 79% [95% confidence interval (CI) 60-91] and a specificity of 100% (95% CI 76-100) in predicting malignancy. Galectin-3 had a sensitivity of 79% (95% CI 56-91) and a specificity of 75% (95% CI 47-91) in predicting malignancy. Combining HK III, cyclin A and galectin-3 in a parallel test increased the sensitivity to 96% (95% CI 80-99) while the specificity remained at a high level of 75% (95% CI 47-91). Leave-one-out cross-validation demonstrated a stable predictive validity of a model based on HK III, cyclin A and galectin-3. CONCLUSIONS: In this study, we have demonstrated that in addition to galectin-3, HK III and cyclin A profiles could be important biomarkers in predicting malignancy in follicular thyroid nodules. The use of these biomarkers may allow an accurate preoperative diagnosis of thyroid cancer, which can be cost saving and may avoid serious morbidity such as vocal cord paralysis. The value of the suggested biomarkers warrants further evaluation in a large prospective study on cytological samples of follicular thyroid nodules.

[From the Cochrane Library: Phosphodiesterase inhibitors are effective in treating erectile dysfunction in diabetic men]. / Uit de Cochrane Library: fosfodiësteraseremmers effectief bij diabetici met erectiestoornissen.

Erectile dysfunction is a common multifactorial complication of diabetes mellitus. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. A recent Cochrane systematic review assessed the effects ofPDE-5 inhibitors in patients with diabetes mellitus and erectile dysfunction from 8 randomized placebo-controlled trials (a total of 1759 participants). The duration of therapy was mainly 12 weeks. The weighted mean difference (WMD) for the International Index of Erectile Function (erectile dysfunction domain) at the end of the study period was 6.6 in favour of the PDE-5 inhibitors arm. The relative risk for answering 'yes' to a global efficacy question ('did the treatment improve your erections?') was 3.8 in the PDE-5 inhibitors arm compared with the control arm. Headache and flushing were the most common adverse events, followed by flu-like symptoms, dyspepsia, myalgia, vision disorders and lower back pain. The overall risk ratio for developing any adverse reaction was 4.8 in the PDE-5 inhibitors arm as compared to the control arm. It was concluded that sufficient evidence exists that treatment with PDE-5 inhibitors can improve erectile dysfunction in diabetic men.

[From the Cochrane Library: Marginally higher chance of cure by antibiotic treatment in acute bacterial conjunctivitis]. / Uit de Cochrane Library: Marginaal grotere genezingskans door antibioticabehandeling bij acute bacteriële conjunctivitis.

Acute bacterial conjunctivitis is one of the most frequently encountered ocular disorders in primary care. It is frequently self-limiting, and the widespread use of broad-spectrum antibiotics has led to concerns regarding antibiotic resistance. Therefore, a Cochrane systematic review of 5 randomised clinical trials that compared antibiotic treatment with placebo in patients with acute bacterial conjunctivitis was recently updated. The chances of clinical and microbiological benefits of topical antibiotics were small but statistically significantly higher compared with placebo in the early stage (2 to 5 days after the first day of the intervention) and late stage (6 to 10 days after the first day of the intervention). The risk of adverse events in patients treated with placebo appeared to be low. Future trials should assess the cost-effectiveness of antibiotic treatment for acute bacterial conjunctivitis.

[18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase i expression in the primary tumor.

Patients suspected of recurrent differentiated thyroid cancer (DTC) may require "blind" (131)I therapy, with the disadvantage of unpredictable efficacy and toxicity. Alternatively, positron emission tomography (PET) with [(18)F]fluorodeoxyglucose ((18)FDG) can document the recurrence, thereby rationalizing therapeutic options. This study compared (18)FDG uptake in vivo with biomarkers expected to be involved in the underlying biological mechanisms. Additionally, we investigated whether such features were present in the primary tumors. Preoperatively, 19 patients with recurrent DTC underwent PET. (18)FDG uptake was compared with histological and immunohistochemical features in surgical specimens of recurrent and primary tumor. Thirteen of 19 recurrences were positive at PET, and (18)FDG uptake was associated with the expression of hexokinase type I (HK I; P = 0.011). All lesions with HK I overexpression were positive on (18)FDG PET. HK I expression in the original primary tumor and the metastases was similar in 82% (rho = 0.648; P = 0.005). In suspected recurrent thyroid cancer, stratification for (18)FDG PET may benefit from pretest immunohistochemical analysis of HK I of the primary tumor, as HK I negativity indicates a low likelihood of PET positivity.

[A national prospective trial register for randomised controlled trials: ethical and practical necessity]. / Een nationaal prospectief trialregister voor gerandomiseerde en gecontroleerde trials; ethisch en praktisch noodzakelijk.

The decision to treat a patient is often based on the results of randomised controlled trials (RCTs). These important investigations inform physicians and patients with regard to the chance of favourable results of treatment and the risks of adverse reactions. However, research has shown that especially the smaller RCTs in which no or even an adverse effect of new interventions is found run a relatively high risk of remaining unpublished, which leads to publication bias and an overestimate of the efficacy of an intervention. This is undesirable. The best way to identify possible publication bias and reduce its negative effects is to register RCTs from their starting date onwards in a prospective and publicly accessible register. Other motives for such a register are the prevention of duplication of research work and its financial support, and informing patients. Currently, a prospective Dutch national trial register is being developed by the Dutch Cochrane Centre. This is not only of importance to researchers and patients, but also to grant-providing bodies and the editors of medical scientific journals.

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.

Diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography in the follow-up of papillary or follicular thyroid cancer.

Positron emission tomography with 18F-fluorodeoxyglucose is a relatively new nuclear imaging technique in oncology. We conducted a systematic review to determine the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography in patients suspected of recurrent papillary or follicular thyroid carcinoma. Two reviewers independently selected, extracted, and assessed data from relevant literature found in computerized databases and by reference tracking. Prospective and retrospective studies with 10 human subjects, or more, that evaluated the accuracy of ring positron emission tomography, using 18F-fluorodeoxyglucose in follicular and papillary thyroid cancer, were included. Studies on 18F-fluorodeoxyglucose imaging using gamma cameras, reviews, case reports, editorials, letters, and comments were excluded. The methodological quality was assessed by applying the criteria for diagnostic tests recommended by the Cochrane Methods Group on Screening and Diagnostic Tests. A rating system was used for qualitative analysis consisting of four levels of evidence (1 = highest level; 4 = lowest level). Fourteen studies met the inclusion criteria. All studies claimed a positive role for positron emission tomography but, at evidence levels 3 or 4, precluding quantitative analysis. Methodological problems included poor validity of reference tests and a lack of blinding of test performance and interpretation. The reviewed material was heterogeneous with respect to patient variation and validation methodology. The most consistent data were found on the ability of 18F-fluorodeoxyglucose positron emission tomography to provide an anatomical substrate in patients with elevated serum Tg and negative iodine-131 scans. In conclusion, the results seem to support the potential of 18F-fluorodeoxyglucose positron emission tomography to identify and localize foci of recurrent cancer in the latter patient subset. However, implementation of positron emission tomography in a routine diagnostic algorithm requires additional evidence.

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 searching.

Chemokine IP-10 expression in cultured human keratinocytes.

IP-10, a member of the CXC family of chemokines, is considered to play an important role in inflammation via its T-cell chemotactic and adhesion-promoting properties. Elevated IP-10 levels in the epidermis of psoriasis, delayed-type hypersensitivity reactions, cutaneous T-cell lymphoma and fixed drug eruptions prompted us to study its expression in keratinocytes. IP-10 mRNA could be detected using the sensitive RT-PCR method, but not by Northern blotting in RNA preparations from unstimulated normal cultured keratinocytes, indicating a low steady-state level of IP-10 mRNA. Upon stimulation with IFN-gamma, IP-10 mRNA was found to accumulate in high amounts in a time- and dose-dependent manner. Superexpression was found with the combination of IFN-gamma and TNF-alpha or IL-1, although these latter cytokines by themselves did not induce accumulation of IP-10 mRNA. Nuclear run-on experiments performed to investigate the regulation of IP-10 mRNA expression, showed a very high constitutive transcriptional activity of the IP-10 gene in unstimulated keratinocytes, which was not affected by stimulation with IFN-gamma, TNF-alpha, or a combination of IFN-gamma and TNF-alpha. Protein kinase C (PKC) was shown to be involved in IP-10 mRNA expression since the PKC inhibitor H7 decreased IP-10 mRNA accumulation. A protein was isolated from culture supernatants of stimulated keratinocytes using HPLC techniques and, by sequence analysis, was found to be identical to IP-10. The dynamics of secretion of IP-10 protein as monitored by ELISA was shown to parallel the mRNA expression.