5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Therapeutic effect of ferrous sulfate in diabetic patients with iron deficiency anaemia: a randomised controlled trial.

Iron deficiency anaemia (IDA) and diabetes mellitus (DM) are most prevalent disease, that diabetic patients are more prone to IDA. Therefore, the main aim of this study was to investigate the relationship between patients with diabetes and IDA in relation to taking iron pills daily and every other day to reduce the effects related to it. Ninety-one participants were enroled and randomly divided into two groups, with a final analysis cohort of 72 patients. The primary focus was on changes in serum Hb and Ferritin levels. The screening phase lasted 24 weeks, leading to 72 eligible participants meeting the criteria for entry into the study. Additionally, the study examined alternations in Hb and Hb A1C levels after treating patients with iron deficiency. The Hb and ferritin level contrasts between groups were not significant (P = 0.096 and P = 0.500, respectively). The relationship between Hb A1C and Hb levels before and after treatment was positive and significant (r 2 = 0.187). The results of the present study show that although the effectiveness of using oral iron supplements did not have a significant difference in terms of increasing haemoglobin and ferritin, the use of oral iron once every other day was more effective than the use of oral iron every day, and also in this study Like other studies, this result concluded that there is a negative correlation between Hb A1C and Hb, and to check the status of Hb A1C in diabetics, the level of Hb should be considered first.

The effect of mobile-app-based instruction on the physical function of female patients with knee osteoarthritis: a parallel randomized controlled trial.

BACKGROUND: Osteoarthritis is a common disease and one of the most important causes of disability in the elderly that negatively affect the quality of their life. The purpose of this study was to evaluate the effectiveness of mobile app-based-instruction in improving physical performance of female patients with knee osteoarthritis. METHODS: The present study was a randomized clinical trial. The sample included 64 female patients (40 to 70 years old) with knee osteoarthritis in Bojnurd city in 2018. They were selected from the available patients that were randomly divided into comparison and intervention groups. Before the intervention, demographic information questionnaire, Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire, and 36-item short-form health survey (SF-36) were employed to elicit data on demographic information, arthritis condition and health status of the participants. Intervention lasted for a period of two months for each group. Intervention group received mobile-app-based instruction coupled with routine cares, while comparison group just received the routine cares. After the intervention both groups were evaluated again in terms of arthritis condition and health status using the same scales. RESULTS: After the intervention, significant differences were found between the intervention and comparison groups in terms of overall WOMAC score (p = 0.005), pain aspect of WOMAC (p = 0.005), physical function aspect of WOMAC (p = 0.005), physical function aspect of SF-36 (p ≤ 0.05), and vitality aspect of SF-36 (p > 0.05). CONCLUSION: The use of mobile-app-based instruction can enhance the physical function and quality of life in patients with knee osteoarthritis. Trial registration The research project was registered at Iranian Registry of Clinical Trials (IRCT20161208031300N2).

Does atorvastatin have augmentative effects with sodium valproate in prevention of migraine with aura attacks? A triple-blind controlled clinical trial.

BACKGROUND: Migraine is a painful and disabling nervous disorder which negatively affects the quality of life. Migraineurs may suffer from a generalized vasomotor dysfunction. Statins improve vasomotor and vascular function, with their pleiotropic effects. We aimed to assess efficacy and safety of adding Atorvastatin to prophylactic regimen in better control of migraine with aura. METHODS: This triple-blind controlled clinical trial was on 68 patients with migraine with aura. An interval of at least 1 month was given to evaluate vitamin D3 level and eligibility. In patients with vitamin D3 deficiency, the correction with vitamin D supplementation was provided. The patients were randomly assigned to receive atorvastatin 20 mg plus sodium valproate 500 mg or placebo plus sodium valproate 500 mg once a day for 2 months. The patients were evaluated based for the number of attacks and pain severity based on Visual Analogue Scale. RESULTS: There was a significant (p = 0.0001) improvement in severity of pain and number of migraine attacks by adding Atorvastin to the prophylactic regimen of patients with migraine with aura. After controlling for variable parameters, the differences between two arms of the study was yet statistically significant (p = 0.0001). A significant number of participants in intervention group were satisfied by their treatment (p = 0.001) with no remarkable side effects (P = 0.315). CONCLUSIONS: Adding atorvastatin to migraine with aura preventive regimen may help reduce the number of acute attacks and pain severity without causing considerable side effects and led to a better patient satisfaction. TRIAL REGISTRATION: IRCT20180106038242N1 . Registered: 7 February 2018.

Evolution of hydrogels for cartilage tissue engineering of the knee: A systematic review and meta-analysis of clinical studies.

INTRODUCTION: In recent years, studies have boosted our knowledge about the biology and disorders of articular cartilage. In this regard, the design of hydrogel-based scaffolds has advanced to improve cartilage repair. However, the efficacy of knee cartilage repair using hydrogels remains unclear. The aim of systematic review and meta-analysis was to scrutinize the efficiency of hydrogel-based therapy in correcting cartilage defects of knee (femoral condyle, patella, tibia plateau and trochlea). METHODS: The search was conducted in PubMed to gather articles published from 2004/1/1 to 2019/10/01, addressing the effects of implant of hydrogel on knee joint cartilage regeneration. The Cochrane Collaboration's tool for estimating the risk of bias was applied to check the quality of articles. The clinical data for meta-analysis was recorded using the visual analog scale (VAS), Lysholm score, WOMAC, and IKDC. The guidelines of Cochrane Handbook for Systematic Reviews of Interventions were utilized to conduct the review and meta-analysis in the RevMan 5.3 software. RESULTS: The search resulted in 50 clinical trials that included 2846 patients, 986 of whom received cell-based hydrogel implants while 1860 patients used hydrogel without cell. There were significant differences comparing the pain scores based on the VAS (MD: -2.97; 95% CI: -3.15 to -2.79, P<0.00001) and WOMAC (MD: -25.22; 95% CI: -31.22 to -19.22, P<0.00001) between pre- and post-treatment with hydrogels. Furthermore, there were significant improvements in the functional scores based on the IKDC total score (MD: 30.67; P<0.00001) and the Lysholm knee scale (MD: 29.26; 95% CI: 26.74 to 31.78, P<0.00001). According to the Lysholm and IKDC score and after cumulative functional analysis, there was a significant improvement in this parameter (MD: 29.25; 95% CI: 27.26 to 31.25, P<0.00001). CONCLUSIONS: This meta-analysis indicated clinically and statistically significant improvements in the pain score (VAS and WOMAC) and the functional score (IKDC and Lysholm) after the administration of hydrogel compared to pretreatment status. So, the current evidence shows the efficiency of hydrogel-based therapy in correcting and repairing knee cartilage defects.

Statin for Migraine Headache: Is It Worthwhile?

Migraine is a severe primary headache disorder that affects about 12% of the population, and it often occurs along with nausea, vomiting, and extreme sensitivity to light and sound. For patients with migraine, beta-blockers, antidepressants, anticonvulsants, are given as the first line of preventive treatment; alternatives include calcium channel blockers. Not only statins prevent the synthesis of cholesterol biosynthesis but also they have a pleiotropic effect such as antiinflammatory effects, antioxidant property, antiproliferative and immunomodulatory effects, the stability of plaque, normalization of sympathetic outflow, and inhibit of platelet aggregation. Here, we should focus on the evidence that works on the effect of the statins on migraine headaches, especially in patients who do not respond to first-line prevention treatments. The hypothesis may show that statins could be effective in the treatment of patients with migraine. Taken together, some epidemiologic, clinical, and experimental evidence suggest that statin may be a novel and promising candidate. For future treatment or prophylaxis of migraine, we hope that the use of this drug as cholesterol and triglycerides(blood lipids) leads to rebate drugs, as well as to reduce migraine headaches episodes agent to enhance the role of this drug in cure or prevent migraine attacks or recurrence, and finally to improve the patient's quality of life.

Prevalence of osteoporosis and osteopenia in men and premenopausal women with celiac disease: a systematic review.

BACKGROUND: Celiac disease (CD) is known as a reason of metabolic osteopathy. Progression of non-invasive methods such as bone densitometry has shown that an important ratio of CD cases is faced with impaired bone mass and such cases are prone to bone fractures. Variety of low bone mineral density in CD is probably because of ignored confounding factors such as age, menopause, and drug. The aim of our study was to systematically review the osteoporosis and osteopenia incidences among premenopausal females and males with CD. METHODS: This systematic review was done based on preferred reporting items for systematic reviews (PRISMA) guidelines. PubMed and Scopus and Cochran databases were searched according to the relevant medical subject headings (MeSH) of CD and bone mineral density until 2018. Prevalence of osteopenia and osteoporosis were used as effect size for meta-analysis. Cochrane Q (p < 0.05) and I2 index were presented to reveal the heterogeneity. RESULTS: 54 eligible full text reviews were included and nineteen selected for data extraction. Eleven articles didn't have our inclusion criteria and had ignored confounding factors like age and menopause, and we excluded; data extraction was done in eight studies. A total of 563 premenopausal women and men who were from, UK, Brazil, India, Hungary, and Poland were included. The pooled prevalence of osteoporosis was 14.4% [95%CI: 9-20.5%] (Cochrane Q = 7.889, p = 0.96, I2 = 49.29%), and osteopenia was 39.6% [31.1-48.8%] (Cochrane Q = 14.24, p = 0.07, I2 = 71.92%), respectively. CONCLUSION: Our findings suggest that bone loss is more prevalent in celiac disease and can be associated with increased risk of fracture. However, but results are pooled prevalence and we need more case -control studies with more sample size and consideration of confounding factors.

Validating a Drug-Related Problems Classification System in Outpatient Setting in Iran.

OBJECTIVE: Medication Therapy Management service (MTMs) has been introduced to improve cooperation among pharmacists and other healthcare professionals in the management of chronic diseases, drug therapy, and patients on polypharmacy. One part of MTMs is detection and resolution of possible drug-related problems (DRPs). Nowadays, numerous DRPs classification systems are available, but due to some defects none of them are currently accepted and implemented universally. The purpose of this study is to design and validate a comprehensive system for classification and documentation of possible DRPs for the Iranian patients. METHODS: In this methodological study, four classification systems were studied, and their differences were reviewed, compared. Ultimately, a comprehensive documentation system was developed and tested for validity using experts' opinions. FINDINGS: A comprehensive list of 53 DRPs under eight categories was developed and examined for validity. After collecting the data and validity assessment, questions with content validity ratio of <0.4 and content validity index of <70% were excluded and modified. Finally, with the exclusion and modification of eight DRPs, a modified DRPs list was created. CONCLUSION: According to the universality and validity assessment and based on consensus of 20 experts, this DRPs list can be used to regulate the standard operation procedure of outpatient clinics in Iran, and could act toward standardization of this service.

The Effect of Self-Management Educational Program on Pain Intensity in Elderly Patients with Knee Osteoarthritis: A Randomized Clinical Trial.

BACKGROUND: Osteoarthritis is one of the chronic diseases that greatly affect the health and life quality of individuals. AIM: This study aimed to determine the effect of self-management educational program on the pain intensity of the elderly patients with knee osteoarthritis. METHODS: In a randomised clinical trial, a total of 82 elderly patients with knee osteoarthritis were randomly divided into intervention and control groups. The intervention group received six sessions of self-management group education, while the control group received only the routine care during this period. In both groups, patients' pain intensity, with a visual analogue scale (VAS), were assessed before, immediately after and eight weeks after the start of the study. RESULTS: The mean pain intensity scores of the intervention and control groups were not significantly different before the intervention (P = 0.9), but after the intervention, the mean pain intensity score in the intervention group (3.61 ± 2.36) was significantly lower than that of the control group (4.93 ± 2.00), (P < 0.0001). CONCLUSION: Implementation of a self-management program for the patients with knee osteoarthritis is useful in reducing their pain intensity and can be used as one of the effective methods for their empowerment.

Comparison of Dabigatran vs. Warfarin in Acute Vnous Thromboemboly: Systematic Review.

Acute Venous Thromboembolism (VTE) is a common disease associated with the significant morbidity and mortality. We reviewed clinical outcomes systematically with Dabigatran as a direct oral anticoagulants (DOAC) for treatment of acute VTE. We used Ovide, PubMed, Cochrane (CENTRAL), EMBASE, Scopus, Science Direct, LILAC(for article written not English) and also Iranian database; Magiran, Isc, Iran Medex, Iran DOC, Doaj up to May 2014 to identify randomized clinical trials of Dabigatran compared with conventional treatment for VTE. Two investigators extracted data independently. Number of 5107 patients including two trails were selected. The risk of recurrent VTE was similar with the Dabigatran and standard treatment (Hazard Ratio, 95% confidence interval 1.09 (0.76-1.57). Dabigatran reduced the risk of minor bleeding in comparison with standard treatment; Warfarin (0.62) (0.50-0.76). Finally-in minor bleeding-the Dabigatran seemed as effective as, and probably safer than standard treatment of acute VTE. But in some aspects such as adherence to treatment, pregnant patient, impact on quality of life, new researches are needed to be clarified.

Efficacy of Sucralfate Mouth Wash in Prevention of 5-fluorouracil Induced Oral Mucositis: A Prospective, Randomized, Double-Blind, Controlled Trial.

Sucralfate has been used for the prevention and treatment of radiotherapy- and chemotherapy-induced stomatitis and mucositis in a number of studies, but the results are contradictory. To answer such discrepancies, the present study was designed to evaluate the efficacy of sucralfate mouthwash in prevention of 5-fluorouracil (5-FU)-induced oral mucositis in patients with gastrointestinal malignancies. Patients with gastrointestinal cancers receiving 5-FU-based chemotherapy regimens were included in this randomized, blinded, controlled trial and were randomly allocated to either sucralfate mouthwash (every 6 h) or placebo. The patients were visited at fifth and tenth day of trial; the presence and severity of oral mucositis and the intensity of pain were assessed. The patients receiving sucralfate experienced lower frequency and severity of mucositis (76% vs. 38.5%, P = 0.005 and 84 vs. 38.5%, P < 0.001, respectively) and less intense pain (2.5 ± 2.2 vs. 5.08 ± 3.82, P = 0.004 and 1.33 ± 0.86 vs. 4.12 ± 3.5, P = 0.001, respectively) compared with the placebo group both at day 5 and day 10. Within the sucralfate group, a decrease in frequency and severity of mucositis was observed throughout the trial period, while in the placebo group no such effect was observed. Sucralfate mouthwash reduced the frequency and severity of 5-FU-induced oral mucositis in patients with gastrointestinal malignancies compared with placebo, indicating its efficacy in the prevention of chemotherapy-induced mucositis.

Developing an Appropriateness Criteria for Knee MRI Using the Rand Appropriateness Method (RAM)-2013.

BACKGROUND: Knee pain is one of the most common reasons patients visit their physician. In this regard Magnetic Resonance Imaging (MRI) is the tool of preference for diagnosis. The aim of this study was to determine appropriate guidelines for knee MRI administration using the RAND Appropriateness Method (RAM)-2013. METHODS: This qualitative study was done in the Mashhad University of Medical Sciences in 2013. The most appropriate approved knee MRI administration clinical guidelines were evaluated using Guidelines Evaluation and Research Appraisal (AGREE). Panel members consisting of six orthopedic and three rheumatologic doctors gave scores ranging from 1 to 9 for each scenario. The indications were grouped as appropriate, equivocal and inappropriate. Data were analyzed by descriptive statistics and SPSS ver. 18 software. RESULTS: Sixty-three scenarios were extracted from the guidelines and then the scenarios were evaluated in 26 indications. Thirty-two (50.79%) cases were considered appropriate, 12 (19.04%) cases uncertain and 19 (30.1%) cases inappropriate. CONCLUSIONS: The RAND appropriateness method is helpful in identifying the opinion of stakeholders in health care systems. Moreover, making practical use of clinical guidelines can improve patients' quality of care and prevent unnecessary costs.

Opening wedge high tibial osteotomy using tibial wedge allograft: a case series study.

High tibial osteotomy has been established as an effective surgical intervention in patients with unicompartment osteoarthritis of the knee associated with varus deformity and abnormal load through the medial compartment. The aims of this study were to report the result of open-wedge osteotomy performed with allograft bone and also to evaluate the postoperative clinical results in a series of patients. There are still little medical literatures regarding the use of an allograft bone transplant in open-wedge osteotomy. 37 consecutive cases that had undergone opening wedge osteotomy using allograft bone were studied. They were followed each 2 months after surgery until 6 month. There were 7 men and 30 women, aged ranging from 16 to 66. All patients were followed 6 months after surgery until clinical and radiographic healing of the osteotomy site. All patients could stand and walk on operated limb 6 months after operation, but 11 of them had still pain after this duration. There were no cases of non-union or osteotomy site collapse associated with the use of allograft. Moreover, no significant complication has been detected in these patients with choosing appropriate patients and performing good surgical technique, and the proximal tibial wedge allograft is a satisfactory choice that provides effective clinical and radiographic bone union.