Uptake pattern of [68Ga]Ga-DOTA-NOC in tissues: implications for inflammatory diseases.

BACKGROUND: [68Ga]Ga-DOTA-NOC binds to somatostatin receptor (SSTR) subtypes 2 and 5, also expressed on lymphocytes and macrophages, but no information is available about uptake in tissues that might be affected by a chronic inflammatory process. Our aim was to obtain normal reference values for: [68Ga]Ga-DOTA-NOC uptake in tissues prone to chronic inflammation. METHODS: Retrospective study in 81 patients who performed the scan for a suspicion of neuroendocrine tumor (NET). We analyzed major joints, salivary glands, thyroid, aortic wall from images acquired after injection of 173.9±1 Mbq of: [68Ga]Ga-DOTA-NOC. We calculated the SUVmax and SUVtarget/SUVgluteus ratio or SUVtarget/SUVaorta ratio. Data are reported as mean±2 or ±3 standard deviations (SD). RESULTS: SUVmax values appeared more reliable than other ratios. In thyroid we found a mean SUVmax of 1.36±0.45, with no values >3SD; in parotid glands 0.98±0.40, with 2 values >3SD; in submandibular glands 0.99±0.37, with 2 values >3SD; in aortic arch 1.71±0.50, with 1 value >3SD; in thoracic aorta 2.03±0.52, with 1 value >3SD; in abdominal aorta 2.19±0.49, with no value >3SD; in shoulders 0.92±0.31 and in hips 0.87±0.34, with 2 and 4 values >3SD, respectively. These 12 values with SUVmax >3SD, belong to 5 patients, 3 of which had signs of xerostomia and/or arthritis. A statistically significant correlation was observed between SUVmax and age in all examined tissues but in the aorta. CONCLUSIONS: Tissues in which lymphocytic infiltration may occur show that SUVmax is tissue-dependent. Within tissue variability, an SUVmax greater than the mean +3SD is rarely found amongst patients without a symptomatic chronic inflammatory process but, when found, may highlight a chronic inflammatory condition.

Authors seldom report the most patient-important outcomes and absolute effect measures in systematic review abstracts.

OBJECTIVES: Explicit reporting of absolute measures is important to ensure treatment effects are correctly interpreted. We examined the extent to which authors report absolute effects for patient-important outcomes in abstracts of systematic review (SR). STUDY DESIGN AND SETTING: We searched OVID MEDLINE and Cochrane Database of Systematic Reviews to identify eligible SRs published in the year 2010. Citations were stratified into Cochrane and non-Cochrane reviews, with repeated random sampling in a 1:1 ratio. Paired reviewers screened articles and recorded abstract characteristics, including reporting of effect measures for the most patient-important outcomes of benefit and harm. RESULTS: We included 96 Cochrane and 94 non-Cochrane reviews. About 117 (77.5%) relative measures were reported in abstracts for outcomes of benefit, whereas only 34 (22.5%) absolute measures were reported. Similarly, for outcomes of harm, 41 (87.2%) relative measures were provided in abstracts, compared with only 6 (12.8%) absolute measures. Eighteen (9.5%) abstracts reported both absolute and relative measures for outcomes of benefit, whereas only two (1.1%) abstracts reported both measures for outcomes of harm. Results were similar between Cochrane and non-Cochrane reviews. CONCLUSION: SR abstracts seldom report measures of absolute effect. Journal editors should insist that authors report both relative and absolute effects for patient-important outcomes.

Systematic reviews experience major limitations in reporting absolute effects.

OBJECTIVES: Expressing treatment effects in relative terms yields larger numbers than expressions in absolute terms, affecting the judgment of the clinicians and patients regarding the treatment options. It is uncertain how authors of systematic reviews (SRs) absolute effect estimates are reported in. We therefore undertook a systematic survey to identify and describe the reporting and methods for calculating absolute effect estimates in SRs. STUDY DESIGN AND SETTING: Two reviewers independently screened title, abstract, and full text and extracted data from a sample of Cochrane and non-Cochrane SRs. We used regression analyses to examine the association between study characteristics and the reporting of absolute estimates for the most patient-important outcome. RESULTS: We included 202 SRs (98 Cochrane and 104 non-Cochrane), most of which (92.1%) included standard meta-analyses including relative estimates of effect. Of the 202 SRs, 73 (36.1%) reported absolute effect estimates for the most patient-important outcome. SRs with statistically significant effects were more likely to report absolute estimates (odds ratio, 2.26; 95% confidence interval: 1.08, 4.74). The most commonly reported absolute estimates were: for each intervention, risk of adverse outcomes expressed as a percentage (41.1%); number needed to treat (26.0%); and risk for each intervention expressed as natural units or natural frequencies (24.7%). In 12.3% of the SRs that reported absolute effect estimates for both benefit and harm outcomes, harm outcomes were reported exclusively as absolute estimates. Exclusively reporting of beneficial outcomes as absolute estimates occurred in 6.8% of the SRs. CONCLUSIONS: Most SRs do not report absolute effects. Those that do often report them inadequately, thus requiring users of SRs to generate their own estimates of absolute effects. For any apparently effective or harmful intervention, SR authors should report both absolute and relative estimates to optimize the interpretation of their findings.

Reporting, handling and assessing the risk of bias associated with missing participant data in systematic reviews: a methodological survey.

OBJECTIVES: To describe how systematic reviewers are reporting missing data for dichotomous outcomes, handling them in the analysis and assessing the risk of associated bias. METHODS: We searched MEDLINE and the Cochrane Database of Systematic Reviews for systematic reviews of randomised trials published in 2010, and reporting a meta-analysis of a dichotomous outcome. We randomly selected 98 Cochrane and 104 non-Cochrane systematic reviews. Teams of 2 reviewers selected eligible studies and abstracted data independently and in duplicate using standardised, piloted forms with accompanying instructions. We conducted regression analyses to explore factors associated with using complete case analysis and with judging the risk of bias associated with missing participant data. RESULTS: Of Cochrane and non-Cochrane reviews, 47% and 7% (p<0.0001), respectively, reported on the number of participants with missing data, and 41% and 9% reported a plan for handling missing categorical data. The 2 most reported approaches for handling missing data were complete case analysis (8.5%, out of the 202 reviews) and assuming no participants with missing data had the event (4%). The use of complete case analysis was associated only with Cochrane reviews (relative to non-Cochrane: OR=7.25; 95% CI 1.58 to 33.3, p=0.01). 65% of reviews assessed risk of bias associated with missing data; this was associated with Cochrane reviews (relative to non-Cochrane: OR=6.63; 95% CI 2.50 to 17.57, p=0.0001), and the use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (OR=5.02; 95% CI 1.02 to 24.75, p=0.047). CONCLUSIONS: Though Cochrane reviews are somewhat less problematic, most Cochrane and non-Cochrane systematic reviews fail to adequately report and handle missing data, potentially resulting in misleading judgements regarding risk of bias.

Antifungal prophylaxis following heart transplantation: systematic review.

Patients with heart transplantation have a high incidence of infectious complications, especially fungal infections. The aim of the systematic review was to determine the best pharmacological strategy to prevent fungal infections among patients with heart transplant. We searched the PubMed and Embase databases for studies reporting the effectivenesss of pharmacologic strategies to prevent fungal infections in adult patient with a heart transplant. Our search yielded five studies (1176 patients), four of them with historical controls. Two studies used inhaled amphotericin B deoxycholate, three used itraconazole and one used targeted echinocandin. All studies showed significant reduction in the prophylaxis arm. Different products, doses and outcomes were noted. There is a highly probable benefit of prophylaxis use, however, better studies with standardised doses and comparators should be performed.

A methodological survey of the analysis, reporting and interpretation of Absolute Risk ReductiOn in systematic revieWs (ARROW): a study protocol.

BACKGROUND: Clinicians, providers and guideline panels use absolute effects to weigh the advantages and downsides of treatment alternatives. Relative measures have the potential to mislead readers. However, little is known about the reporting of absolute measures in systematic reviews. The objectives of our study are to determine the proportion of systematic reviews that report absolute measures of effect for the most important outcomes, and ascertain how they are analyzed, reported and interpreted. METHODS/DESIGN: We will conduct a methodological survey of systematic reviews published in 2010. We will conduct a 1:1 stratified random sampling of Cochrane vs. non-Cochrane systematic reviews. We will calculate the proportion of systematic reviews reporting at least one absolute estimate of effect for the most patient-important outcome for the comparison of interest. We will conduct multivariable logistic regression analyses with the reporting of an absolute estimate of effect as the dependent variable and pre-specified study characteristics as the independent variables. For systematic reviews reporting an absolute estimate of effect, we will document the methods used for the analysis, reporting and interpretation of the absolute estimate. DISCUSSION: Our methodological survey will inform current practices regarding reporting of absolute estimates in systematic reviews. Our findings may influence recommendations on reporting, conduct and interpretation of absolute estimates. Our results are likely to be of interest to systematic review authors, funding agencies, clinicians, guideline developers and journal editors.

Drugs for treating giardiasis.

BACKGROUND: Giardiasis infection may be asymptomatic, or can cause diarrhoea (sometimes severe), weight loss, malabsorption, and, in children, failure to thrive. It is usually treated with metronidazole given three times daily for five to 10 days. OBJECTIVES: To evaluate the relative effectiveness of alternative antibiotic regimens for treating adults or children with symptomatic giardiasis. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6 2012); MEDLINE, EMBASE, LILACS and the International Clinical Trials Registry Platform Search Portal (3 July 2012). SELECTION CRITERIA: We included randomized controlled trials (RCT) comparing metronidazole administered for five to 10 days with any of the following drugs: metronidazole (single dose), tinidazole, albendazole, mebendazole, and nitazoxanide. The primary outcomes were parasitological and clinical cure. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, performed the risk of bias assessment, and extracted data. We summarized data using risk ratios and mean differences and we presented the results in forest plots and performed meta-analyses where possible. We assessed heterogeneity using the Chi(2) test, I(2) statistic and visual inspection; and we explored this by using subgroup analyses.We assessed the quality of evidence by using the GRADE approach. MAIN RESULTS: We included 19 trials, involving 1817 participants, of which 1441 were children. Studies were generally small, with poor methods reporting. . Most reported parasitological outcomes rather than clinical improvement.Ten trials, from India, Mexico, Peru, Iran, Cuba, and Turkey, compared albendazole (400 mg once daily for five to 10 days) with metronidazole (250 mg to 500 mg three times daily for five to 10 days). This once-daily regimen of albendazole is probably equivalent to metronidazole at achieving parasitological cure (RR 0.99, 95% CI 0.95 to 1.03; 932 participants, 10 trials; moderate quality evidence), and improving symptoms (RR 0.98, 95% confidence interval (CI) 0.93 to 1.04; 483 participants, five trials; moderate quality evidence), but the duration of follow-up was short (two to three weeks). Albendazole probably has fewer side effects than metronidazole (gastrointestinal side effects: RR 0.29, 95% CI 0.13 to 0.63; 717 participants, eight trials; moderate quality evidence; neurological side effects: RR 0.34, 95% CI 0.18 to 0.64; 453 participants, five trials; low quality evidence).Five trials from Turkey, Spain and the UK compared mebendazole (200 mg three times daily for five to 10 days) with metronidazole (5 mg/kg (or 250 mg) three times daily for five to 10 days). These trials were small in size, and at high risk of bias. Consequently, reliable conclusions on the relative effectiveness cannot be made (very low quality evidence).Five further trials, from Iran, Spain and Peru, have evaluated shortened regimens of tinidazole (single dose; 179 participants, three trials), metronidazole (single dose; 55 participants, one trial), and nitazoxanide (three days; 55 participants, one trial). Again, these trials were at high risk of bias and too small to reliably detect or exclude important differences (very low quality evidence). AUTHORS' CONCLUSIONS: Albendazole may be of similar effectiveness to metronidazole, may have fewer side effects, and has the advantage of a simplified regimen. Large, high quality trials, assessing clinical outcomes (such as diarrhoea) will help assess further alternatives.

Comportamiento de la TSH y la T4 en una cohorte de pacientes con arritmia cardiaca tratados con amiodarona u otros antiarrítmicos / Behavior of TSH and T4 in a cohort of patients with cardiac arrhythmia treated with amiodarone or other antiarrhythmics

La amiodarona es uno de los antiarrítmicos de uso más extendido, pero de la misma forma es un medicamento con efectos adversos bien conocidos y a múltiples niveles; uno de los más importantes es el que se describe para el tejido tiroideo. Cerca de 80 porciento de los pacientes que la toman de forma indefinida, presentarán algún efecto adverso; sin embargo, menos de 15 porciento la suspenderán. En la glándula tiroides, los mecanismos de lesión se relacionan, por su semejanza estructural, con la levotiroxina, la liberación de altas concentraciones de yodo y la inducción de reactividad inmune, entre otras. No obstante, la mayoría de los pacientes permanece eutiroideos.Este estudio describe la variación de la función tiroidea a corto plazo, en 77 pacientes que recibieron diferentes tipos de antiarrítmicos, que no tenían factores de riesgo asociados a disfunción tiroidea, y que se reclutaron en el servicio de hospitalización. Se tomaron muestras de TSH al inicio y al cabo de tres meses de seguimiento. Se observaron niveles de TSH normales en 26 porciento (43 pacientes) y tendencia a valores más altos en el control al tercer mes en el grupo medicado con amiodarona. De manera adicional, se describió una proporción mayor de trastornos de la función de la glándula tiroides en la población masculina.