Reviews on Recent Clinical Trials - Volume 18, Issue 2, 2023

Adenomyosis lacks approved pharmacological treatment even after decades of its identification. We performed this study to review the status of clinical research on adenomyosis for finding an effective drug therapy and to identify the most common endpoints used in adenomyosis trials. A systematic search was performed in the PubMed and Clinicaltrials.gov registries to identify interventional trials for analysis without any time and language restrictions. Our search revealed that barely 15 drugs have been assessed for the management of adenomyosis from 2001 to 2021. Among these, LNG-IUS was found to be the most evaluated drug, followed by dienogest. In these trials, the most commonly assessed endpoints included VAS, NPRS for pain, haemoglobin and PBAC for menstrual bleeding, uterine volume, and serum estradiol. There appears to be a need for developing a comprehensive score that takes into consideration all disease symptoms as well as incorporates some objective elements to evaluate the disease.

Introduction: Due to the development of the academic field of prosthetics and orthotics (P&O) in recent years, scientific studies in this domain have increased. However, relevant published studies, especially randomized controlled trials (RCTs), are not always of acceptable quality. Therefore, this study aimed to evaluate the methodological and reporting quality of RCTs in the field of P&O in Iran to recognize existing shortcomings. Methods: Six electronic databases, including PubMed, Scopus, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and the Physiotherapy Evidence Database, were searched from January 1, 2000, to July 15, 2022. The Cochrane risk of bias tool was applied to evaluate the methodological quality of the included studies. In addition, the Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist was used to assess the reporting quality of the included studies. Results: 35 RCTs published from 2007 to 2021 were included in our final analysis. The methodological quality of 18 RCTs was poor, and the quality of the rest of the studies was good (n = 7) or fair (n = 10). In addition, the median score (IQR) of the reporting quality of RCTs in accordance with the CONSORT items was 18 (13-24.5) out of 35. The results of the relationship analysis indicated a moderate correlation between the CONSORT score and the publication year of the included RCTs. Nonetheless, there was a low correlation between the CONSORT scores and the journalsa#039; impact factors. Conclusion: The overall methodological and reporting quality of RCTs in the field of P&O in Iran was not found to be optimal. To enhance the methodological quality, some items should be considered more strictly, such as blinding of outcome assessment, allocation concealment, and random sequence generation. Furthermore, the criteria of CONSORT, as reporting quality checklist, should be adopted in writing the papers, especially methods-related items.

Background: Anthracyclines can improve survival in many types of malignancies, but dose-dependent and irreversible results following the use of anthracyclines have been associated with cardiomyopathy. This meta-analysis aimed to compare the effects of prophylactic agents for preventing cardiotoxicity induced following anticancer agents. Methods: In this meta-analysis, Scopus, Web of Science, and PubMed were surfed for articles published by December 30^th, 2020. The keywords were angiotensin128;converting enzyme inhibitor (ACEI), enalapril, captopril, angiotensin receptor blocker, beta blocker, metoprolol, bisoprolol, isoprolol, statin, valsartan, losartan, eplerenone, idarubicin, nebivolol, dihydromyricetin, ampelopsin, spironolactone, dexrazoxane, antioxidants, cardiotoxicity, n-acetyl-tryptamine, cancer, neoplasms, chemotherapy, anthracyclines, doxorubicin, daunorubicin, epirubicin, idarubicin, ejection fraction or a combination of them in the titles or abstracts. Results: A total of 17 articles out of 728 studies examining 2,674 patients were included in this systematic review and meta-analysis. Ejection fraction (EF) values in the baseline, 6-month, and 12-month follow-up in the intervention group turned out to be 62.52 ± 2.48, 59.63 ± 4.85, and 59.42 ± 4.53, whereas in the control group appeared to be 62.81 ± 2.58, 57.69 ± 4.32, and 58.60 ± 4.58, respectively. Through comparison of the two groups, EF was found to increase in the intervention group by 0.40 after 6 months (Standardized mean difference (SMD): 0.40, 95% confidence interval (CI): 0.27, 0.54), thus proving higher than that of the control groups following the cardiac drugs. Conclusion: This meta-analysis showed that prophylactic treatment with cardio-protective drugs, including dexrazoxane, beta blocker, and ACEI drugs in patients undergoing chemotherapy with anthracycline, have a protective effect on LVEF and prevent EF drop.

Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) play a key role in the pathogenesis of osteoarthritis (OA). Recent research showed the involvement of some MMPs in COVID-19, but the results are limited and contradictory. Objective: In this study, we investigated the levels of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10) and TIMP-1 in the plasma of patients with OA after recovery from COVID- 19. Methods: The experiment involved patients aged 39 to 80 diagnosed with knee OA. All study participants were divided into three research groups: the control group included healthy individuals, the group OA included patients with enrolled cases of OA, and the third group of OA and COVID-19 included patients with OA who recovered from COVID-19 6-9 months ago. The levels of MMPs and TIMP-1 were measured in plasma by enzyme-linked immunosorbent assay. Results: The study showed a change in the levels of MMPs in patients with OA who had COVID- 19 and those who did not have a history of SARS-CoV-2 infection. Particularly, patients with OA who were infected with coronavirus established an increase in MMP-2, MMP-3, MMP-8, and MMP-9, compared to healthy controls. Compared to normal subjects, a significant decrease in MMP-10 and TIMP-1 was established in both groups of patients with OA and convalescent COVID-19. Conclusion: Thus, the results suggest that COVID-19 can affect the proteolysis-antiproteolysis system even after a long postinfectious state and may cause complications of existing musculoskeletal pathologies.

Introduction: Hypercapnic respiratory failure (HRF) is one of the most frequent reasons for intensive care unit (ICU) admissions. In this study, we aimed to investigate the risk factors for prolonged ICU stay in HRF patients for longer than 7, 10, and 15 days. Methods: Impact of demographics, vitals at the admission, comorbid disease severity, respiratory parameters, admission diagnosis, noninvasive mechanical ventilation (NIV) application time and settings, arterial blood gas, and blood biochemistry results were analyzed in patients with HRF to investigate risk factors for longer ICU stay. Results: A total of 210 patients who were admitted to ICU with HRF (PaCO2 values of 45 mmHg and higher) were included in this retrospective cohort study. The mean age of the patients was 69 ± 12 years, and the mean ICU duration was 9 ± 7 days. Forty-five percent of the patients stayed in the ICU for more than one week and 10% of them stayed for more than 15 days. Risk factors for a prolonged stay in ICU for more than 7 days were high SOFA score, acute renal failure (ARF) at admission, low PaO2/FiO2 on the 2^nd day of admission, and high TSH level. Low FEV1 and FEV1/FVC ratio, ARF at admission, and low PaO2/FiO2 ratio on the 2nd day of admission were found to be risk factors for prolonged stay in ICU for longer than 10 days. Significant risk factors prolonging the ICU duration for more than 15 days were high SOFA score, low FEV1, low FEV1/FVC ratio (p = 0.008), and hypothyroidism (p = 0.037). FEV1% predicted less than 25.5% and FEV1/FVC% less than 46.5% were significantly associated with ICU stay longer than 10 days. Conclusion: Earlier diagnosis and treatment of patients with hypothyroidism and severe airflow obstruction could shorten the length of ICU stay of hypercapnic patients.

Background: We have recently confirmed that non-pain autonomic dysfunction symptoms occur in fibromyalgia and can be assessed with the 31-item Composite Autonomic Symptom Score (COMPASS 31) instrument. Fibromyalgia patients have been found to have higher scores than matched controls across all six domains of this instrument. Objectives: To analyse the principal components of the autonomic COMPASS 31 domain scores in fibromyalgia patients to understand better the fundamental dimensions of dysautonomia in this disorder. Methods: A principal component analysis of fibromyalgia autonomic domain scores was carried out using a varimax orthogonal rotation with decomposition being based on the correlation matrix and setting a threshold of greater than one for the eigenvalues. Results: Three mutually orthogonal principal components, accounting for over 80% of the total variance, were identified. The first was a function of the secretomotor, orthostatic intolerance and pupillomotor domains; the second was a function of the vasomotor and urinary bladder domains; and the third was a function of the gastrointestinal and orthostatic intolerance domains. There was a positive correlation between symptom domain scores of the Revised Fibromyalgia Impact Questionnaire and the first principal component scores (rs = 0.536, p = 0.006). Conclusion: This analysis has reduced the dimensionality of autonomic dysfunction in fibromyalgia patients from six to three. The internal structure of the fibromyalgia dysautonomia data reflected by these results may help in the elucidation of the aetiology of this complex and difficult-to-treat disorder.

Background: Metastatic castrate-resistant prostate cancer (mCRPC) is a challenging disease, especially in heavily pretreated patients. Androgen pathway inhibitors have contributed to a notable improvement in the overall survival and quality of life in patients with mCRPC during the last decade. Still, a considerable percentage of patients are unable to draw benefits from this drug category and are deprived of a treatment that offers limited toxicity and preserves a good quality of life. The mechanisms leading to this pre-existing or acquired resistance, as well as the possible strategies to overcome this resistance have been put at the center of scientists’ attention. Case Presentation: With the present report we present the case of a 70-year-old patient with mCRPC, who was apparently an enzalutamide non-responder, but a multimodal approach with enzalutamide continuation and irradiation to his symptomatic oligoprogressive disease converted him to a responder with clinical, biochemical and imaging response; furthermore, we discuss the existing data providing evidence for the use of metastasis-directed therapy in combination with androgen pathway inhibitors in order to overcome drug resistance in patients with oligoprogressive disease. Conclusion: A considerable proportion of patients with oligometastatic or oligoprogressive prostate cancer who seem not to respond to androgen pathway inhibitors, such as enzalutamide, due to preexisting or acquired resistance, could benefit from MDT with a multimodal treatment approach. This strategy allows androgen pathway inhibitor continuation beyond biochemical progression and delays the switch to next-line systemic treatment.

Objectives: We evaluated polypharmacy and possible drug-drug interactions (p-DDIs) in hospitalized patients before and after using the SIMDA Computerized Medical Decision Support System (CMDSS). Materials and Methods: We included the prescriptions of ≥ 18 years hospitalized patients in the internal medicine department. We developed and implemented the Hdc.DrApp Physician Order Entry System and the CMDSS SIMDA, which detects p-DDIs and signals dosage adjustment based on renal function. To evaluate the impact of the CMDSS, we made a comparison Before (Survey) / After (Intervention): Survey between Oct/22/2019, and Mar/21/2020, and Intervention between Apr/4/2020 and Sep/3/2020. We analyze prescriptions from the first day and after the first day. We compared the number of drugs, polypharmacy (≥ 5 drugs), excessive polypharmacy (≥ 10 drugs), and p-DDIs. We evaluated differences with the X2 test, Yates correction, Fisher's exact test, ANOVA, and post hoc tests according to their characteristics. Results: We evaluated 2,834 admissions: Survey 1,211 and Intervention 1,623. The number of drugs per patient was 6.02 (± 3.20) in Survey and 5.17 (± 3.22) in Intervention (p < 0.001) on the first day and 9.68 (± 5.60) in Survey and 7.22 (± 4.93) in Intervention (p < 0.001) throughout the hospitalization. Polypharmacy was present in 64% of the Survey and 53% of Interventions (RR: 0.83 (0.78-0.88); and excessive polypharmacy in 14% of the Survey and 10% of Intervention (RR: 0.73, 0.60-0.90). The frequency of total p-DDIs was 1.91/patient (± 4.11) in Survey and 0.35 (± 0.81) in the Intervention (p < 0.001). Conclusions: We developed and implemented the Hdc.DrApp and SIMDA systems that were easy to use and allowed us to quantify and reduce polypharmacy and p-DDIs.