Editor's Choice: Medication-indication knowledge bases: a systematic review and critical appraisal

Objective Medication-indication information is a key part of the information needed for providing decision support for and promoting appropriate use of medications. However, this information is not readily available to end users, and a lot of the resources only contain this information in unstructured form (free text). A number of public knowledge bases (KBs) containing structured medication-indication information have been developed over the years, but a direct comparison of these resources has not yet been conducted.Material and Methods We conducted a systematic review of the literature to identify all medication-indication KBs and critically appraised these resources in terms of their scope as well as their support for complex indication information.Results We identified 7 KBs containing medication-indication data. They notably differed from each other in terms of their scope, coverage for on- or off-label indications, source of information, and choice of terminologies for representing the knowledge. The majority of KBs had issues with granularity of the indications as well as with representing duration of therapy, primary choice of treatment, and comedications or comorbidities.Discussion and Conclusion This is the first study directly comparing public KBs of medication indications. We identified several gaps in the existing resources, which can motivate future research.     

Exploring Challenges of Health System in Iranian Traditional Medicine: A Qualitative Study

BackgroundTraditional medicine is a complete system, including diagnostic methods, etiology and treatment based on interpersonal differences.Owing to a lack of investigations in the field of Iranian traditional medicine as well as its many present challenges, certain studies in this area can prove quite practical in identifying and solving ongoing challenges. This study investigates the challenges of the health system in Iranian traditional medicine in the context of control levers.MethodsThe study was qualitative content analysis. A framework analysis, “Control Knob Approach”, was considered appropriate to promote apprehension of challenges of health systems in Iranian traditional medicine. Data were collected by purposeful sampling through in-depth and semi-structured individual interviews with 35 experts of Iranian traditional medicine. Directed content analysis was used to analyze the data, which extracted the initial codes after performing the recorded interviews on paper and immersing them in the data analysis.ResultsUpon analysis of data by Iranian medicine experts, five main categories including financing, payment system, regulations, behavior and organization were defined alongside 13 subcategories.ConclusionAccording to current challenges and the tendency of society to receive traditional medicine services, as well as the long history of traditional medicine in Iran, fair access to traditional medicine services should be provided. This access must be through the production of indigenous knowledge and the formulation of regulatory and educational policies and guidelines and the empowerment of relevant, healthy, effective, evidence-based and cost-effective forces.     

Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies

Purpose

Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation.

Methods

This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records.

Results

Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1–45.9) versus 30.9 months (19.6–46.8); p?= 0.243); stage B: 18.4 months (11.2–19.4) versus 22.8 months (10.9–34.2); p?= 0.815; and stage C: 8.8 months (7.1–10.8) versus 10.8 months (7.7–12.6); p?= 0.976.

Conclusions

Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

     

Target Motion Management in Breast Cancer Radiation Therapy

BackgroundOver the last two decades, breast cancer remains the main cause of cancer deaths in women. To treat this type of cancer, radiation therapy (RT) has proved to be efficient. RT for breast cancer is, however, challenged by intrafractional motion caused by respiration. The problem is more severe for the left-sided breast cancer due to the proximity to the heart as an organ-at-risk. While particle therapy results in superior dose characteristics than conventional RT, due to the physics of particle interactions in the body, particle therapy is more sensitive to target motion.ConclusionsThis review highlights current and emerging strategies for the management of intrafractional target motion in breast cancer treatment with an emphasis on particle therapy, as a modern RT technique. There are major challenges associated with transferring real-time motion monitoring technologies from photon to particles beams. Surface imaging would be the dominant imaging modality for real-time intrafractional motion monitoring for breast cancer. The magnetic resonance imaging (MRI) guidance and ultra high dose rate (FLASH)-RT seem to be state-of-the-art approaches to deal with 4D RT for breast cancer.Key words: breast cancer, target motion, particle therapy, intrafractional movement     

The impact of repeated cycles of radioligand therapy using [<Superscript>177</Superscript>Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer

Background

[¹⁷⁷Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring.

Methods

Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [¹⁷⁷Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson’s correlation coefficient and the corresponding p values.

Results

None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1° or 2°. There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p?=?0.049), hypertension (p?=?0.001) and pre-existing kidney disease (p?=?0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C.

Conclusion

Renal toxicity in patients treated with [¹⁷⁷Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.

     

Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [<Superscript>177</Superscript>Lu]Lu-PSMA-617

Purpose

Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT.

Methods

CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation.

Results

Fifty-two patients underwent a total of 190 cycles of RLT (3–6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA.

Conclusion

Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles.

     

Analysis of plasminogen activator inhibitor-1, integrin beta3, beta fibrinogen, and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss

Citation
Jeddi‐Tehrani M, Torabi R, Zarnani AH, Mohammadzadeh A, Arefi S, Zeraati H, Akhondi MM, Chamani‐Tabriz L, Idali F, Emami S, Zarei S. Analysis of plasminogen activator inhibitor‐1, integrin beta3, beta fibrinogen and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss. Am J Reprod Immunol 2011; 66: 149–156 Problem To identify the associations of the plasminogen activator inhibitor‐1 (PAI‐1) ?675 4G/5G, beta fibrinogen (BF) ?455G/A, integrin beta 3 (ITGB3) 1565T/C, and methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C polymorphisms with recurrent pregnancy loss (RPL). Method of study Polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP) were performed to assess the frequency of five candidate genetic risk factors for RPL, and the frequencies of the polymorphisms were calculated and compared between case and control groups. Results The BF ?455G/A, MTHFR 677C/T, and 1298A/C polymorphisms were found to be positively, and ITGB3 1565T/C polymorphism negatively, associated with RPL. Homozygosity but not heterozygosity for PAI‐1 ?675 4G/5G polymorphism was significantly higher in patients with RPL than in the control group. The presence of both mutations of MTHFR genes highly increased the risk of RPL. Conclusion The data highlight the importance of thrombophilia screening in patients with RPL.     

Probabilistic neural networks for diagnosis of Alzheimer's disease using conventional and wavelet coherence

Recently, the authors presented an EEG (electroencephalogram) coherence study of the Alzheimer's disease (AD) and found statistically significant differences between AD and control groups. In this paper a probabilistic neural network (PNN) model is presented for classification of AD and healthy controls using features extracted in coherence and wavelet coherence studies on cortical connectivity in AD. The model is verified using EEGs obtained from 20 AD probable patients and 7 healthy/control subjects based on a standard 10-20 electrode configuration on the scalp. It is shown that extracting features from EEG sub-bands using coherence, as a measure of cortical connectivity, can discriminate AD patients from healthy controls effectively when a mixed band classification model is applied. For the data set used a classification accuracy of 100% is achieved using the conventional coherence and a spread parameter of the Gaussian function in a particular range found in this research.