Reviews on Recent Clinical Trials - Volume 12, Issue 3, 2017

Background: Primary dysmenorrhea is common among young girls and childbearing women. Dysmenorrhea is a painful contraction of uterus which occurs in the beginning of bleeding or before the menstrual cycle begins. Regarding the mechanism of calcium in response to hormonal change and the role of fish oil on reducing prostaglandins, we compared the effectiveness of fish-oil and calcium supplementation in treating primary dysmenorrheal. Methods: This randomized double-blinded clinical trial was conducted on women aged 18 to 45 years with moderate to severe primary dysmenorrhea symptoms from January 2015 to March 2015. The women were randomly divided to two groups (fish oil and calcium). The drugs were given every day in the first cycle and from 8 days before till 2 days after initiation of menstruation for the second and third cycles. The intensity of pain and other symptoms of dysmenorreha were recorded and data were analyzed in SPSS 16 using T-test and X2 tests. Significant level was considered to be less than 0.05. Results: The mean ± SD age of the patients in the fish oil group was 25.0±4.3 and in calcium group was 25.48±6.6 years. According to this result, there was no statistically significant difference in the intensity of pain between fish-oil group and calcium group before and 1 month after the study (P>0.05). However, there was statistically significant difference between fish-oil group and calcium group before the study and 2 months (P=0.001) and 3 months after study (p<0.001). Besides, the fishoil patients needed less analgesic as compared to the calcium patients. Conclusion: It is concluded that omega-3 is more effective than calcium, what can be justified by pain mechanisms and symptoms pathology in dysmenorrheal.

Background: This study was aimed to compare the efficacy of customized patient-specific titanium mesh based on 3D printed model with intra-operative bending of titanium mesh for reconstructing of orbital floor fracture. Methods: This study was prospectively conducted on 10 patients with unilateral orbital floor fractures caused by accident or falls. In intervention group (n=5), the CT-scan slices were used for generating 3D reconstruction of both affected and unaffected orbits. Then, a 3D printed template of mirrored unaffected orbit was produced to mold the titanium mesh. The titanium mesh in conventional group (n=5) was bended only manually and intraoperatively by surgeon and positioned over the bony defect. All patients were followed-up within 1 week, 1 month and 4 months after surgery for assessing enophthalmos, diplopia and other complications. Results: Of 10 patients of the study only two patients in intervention group had preoperative vertical dystopia or diplopia which had been resolved after intervention. The mean enophthalmos at baseline and 1 week, 1 month and 4 months after surgery in control group were 3.8±0.7, 2.4±0.8, 2.4±0.8, and 2.4±0.8 mm, respectively, and in intervention group were 2.6±0.8, 0.35 ± 0.4, 0.35 ± 0.4 and 0.35 ± 0.4 mm, respectively. The mean enophthalmos did not differ significantly at baseline between two groups, while two groups showed significant difference after surgery. Conclusion: Finally, we concluded that the placement of patient-specific titanium implant for reconstructing of orbital bone fracture led to better outcomes when compared to manual bending in terms of enophthalmos and other complications.

Background: Sofosbuvir is a direct-acting antiviral drug used to treat chronic hepatitis C infection. In 2015, Gilead Sciences, the manufacturer of sofosbuvir, warned that bradycardia could occur when sofosbuvir is administered in combination with amiodarone. Interestingly, among the reported cases of patients with sofosbuvir and amiodarone related bradycardia, some of them were also treated with propranolol. Objective: We herein report a case of ventricular extrasystoles within three hours after the coadministration of sofosbuvir-containing regimen with propranolol. This patient had never been treated with amiodarone. After the sofosbuvir-containing regimen was stopped, ventricular extrasystoles disappeared within 24 hours. This observation suggests that the association of sofosbuvir with propranolol may have a role in the emergence of cardiac arrhythmia. Conclusion: Patients treated with amiodarone and/or propranolol should be continuously monitored within the early hours following the initiation of sofosbuvir.

Background: Despite the high prevalence of viral hepatic cirrhosis all over the world, the characteristic motor features of related Parkinsonism (extrapyramidal manifestations) are not well described. The current study aimed to characterize such disorder in a sample of Egyptian patients with chronic viral liver disease (CLD), and their clinical correlates. Methods: Ninety-six (96) patients with CLD were examined for the presence of extrapyramidal signs. Parkinsonism was assessed using the UPDRS-III scale and its sub scores. Ataxia and dystonia were also assessed by related scales. Patients with Parkinsonism were compared to other patients and correlations with clinical features of CLD were done. Results: The clinical diagnosis of extrapyramidal manifestations was justified in 57 patients (59.4%) with predominant akinetic rigid syndrome (ARS) (87.7%). Bradykinesia and axial features were the most frequent signs (89.5% and 70.2%, respectively). 38.6% of patients had postural tremors, whereas only 3.5% had rest tremors. Gait and postural abnormalities were detected in 38.6% and 36.8% respectively. Parkinsonism was associated with advanced hepatic cirrhosis (p=0.02) and increased episodes of hepatic encephalopathy (HE) (p=0.006). Severity of parkinsonian features was correlated to patients' age, age of onset of CLD and rapid progression, while impaired speech and gait were rather correlated to a number of episodes of HE. Conclusion: Advanced viral cirrhosis is associated with high prevalence of parkinsonism that is characterized by symmetrical ARS with frequent axial features, postural tremor, gait and postural impairment. Severity of these signs is correlated to age, age of onset, rapid progression and frequency of HE.

Background: Human immunodeficiency virus (HIV) affects lymphocytes, resulting in acquired immunodeficiency syndrome. Oxidative stress may play an important role in HIV pathogenesis. Melatonin has antioxidant, antiinflammatory and immunomodulatory effects. Objective: The aim of this study was to evaluate salivary melatonin levels in HIV-positive patients and a healthy control group. Methods: Forty-nine HIV-positive and 49 healthy subjects were included in this study. Patients' drug consumption and clinical examination results were registered in questionnaires. Unstimulated whole saliva was collected in the morning. The melatonin levels were measured by melatonin ELISA kits. Statistical analyses were performed with STATA 12, using t-test and chi-squared test. Results: Salivary melatonin levels were significantly lower in the case group in comparison with the healthy control group (P=0.001). Age was significantly higher in the case group. Chi-squared test showed no statistically significant difference between the case and control groups in smoking (P=0.591) and addiction (P=0.204) but gender differences were observed (P=0.001). Conclusion: Salivary melatonin level as an antioxidant was lower in HIV-positive patients. Further studies are necessary to understand the exact role of melatonin in HIV-positive patients and its therapeutic effects.

Background: An aging HIV-1-infected population warrants examination of the acceptability of individual antiretroviral regimens. In a previous study of ritonavir-boosted darunavir (ARTEMIS), similar safety/efficacy profiles were observed in younger (≤45 years) and older (>45 years) HIV-1-infected subjects. Objective: To evaluate safety and efficacy outcomes in HIV-1-infected younger versus older subjects treated with cobicistat-boosted darunavir. Method: In a 48-week, phase 3b, open-label trial, HIV-1-infected adults were administered darunavir 800 mg and cobicistat 150 mg once-daily with 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs). Post hoc analyses examined safety and efficacy outcomes in subjects ≤45 and >45 years. Results: Of 313 subjects, 76% were ≤45 years (median [range] age, 31 [18-45]) and 24% were >45 years (49 [46-72]). Baseline median (range) viral loads were 4.75 (2.6-6.8) and 4.83 (2.7-7.0) log10 copies/mL, and CD4+ counts were 379.0 (5-1473) and 310.5 (6-757) cells/mm3 in younger and older subjects, respectively. Through Week 48, similar proportions of younger and older subjects had ≥1 adverse event (AE; 93% vs 88%), ≥1 grade 2-4 AE possibly related to study drug (13% vs 15%), and discontinued study due to AE (3% vs 3%). At Week 48, 82% of younger and 78% of older subjects had viral load <50 copies/mL (95% CI of the difference: -7.4% to 13.8%). A higher proportion of older versus younger subjects took >4 concomitant medications during the study (69% vs 57%). Conclusion: Safety and efficacy profiles of cobicistat-boosted darunavir with 2 N(t)RTIs were similar in HIV-1-infected subjects ≤45 and >45 years.

Background: There are limited scientific investigations on cognitive remediation in elderly patients with schizophrenia. The present study was aimed to examine the efficacy of cognitive remediation therapy on social skills in institutionalized elderly patients with schizophrenia. Methods: The study employed a randomized clinical trial. A total of 60 institutionalized elderly patients with schizophrenia from Razi Psychiatric Hospital, Tehran were selected and randomly allocated into two equal groups (control and intervention). The intervention group attended to cognitive remediation therapy for 8 weeks. The Evaluation of Living Skills Scale for psychiatric patients was used for data collection. The Chi Square, independent and paired t-tests using SPSS, version 22, were employed to analyze the data. Results: The mean age of 60 elderly patients participated in the study was 65.25 ± 4.19 years. No significant differences were found between two groups at baseline. However, independent t-tests showed significant differences between the intervention and the control group in social skills after implementation of intervention. Additionally, the results of paired t-tests revealed significant improvements in intervention group on communication skills (t=5.50, p<0.001), behavioral problems with others (t=5.44, p<0.001), and self-care (t=4.70, p<0.001). No significant differences were observed from pretest to post test in control group. Conclusion: The results of the present study may support the efficacy of cognitive remediation therapy on social skills of elderly patients with schizophrenia.

Introduction: 13C-urea breath test (UBT) is a non-invasive test for detecting active H. pylori infection. Previous studies showed a correlation of delta over baseline (DOB) values with bacterial load, mucosal inflammation and successful eradication. Gender has been shown to affect DOB in children. Aim of our study was to verify whether gender or ethnicity affects DOB in adults. Patients and Methods: We retrospectively analyzed data of 2922 patients (1024M/1898F mean age 47±15 years) that underwent UBT in our outpatient unit, from October 2015 to October 2016. Patients were divided based on gender and ethnicity; mean DOB values were then compared. Results: 686 pts (23.4%, 258M/428F, mean age 45±17 years) of 2922 pts showed a positive UBT. Prevalence of H. pylori infection was significantly higher in males compared to females (29% vs 22%; p=0,03). Females showed a significant higher mean DOB (34±25 vs 27,6±22; p=0,008). A total of 2922 UBT were performed during the study period (F:1898, 65%; M: 1024 35%). The prevalence of H. pylori infection is 32% in those from Eastern Countries, 28% in those from South America and 40% in both those coming from Africa and Asia. We found significantly lower DOB values in Italians compared to non-Italian (mean DOB 36±27 vs 69±32; p<0.0001). Conclusion: Our study showed that in our geographic area, prevalence H. pylori infection is higher in males. Moreover, it demonstrates for the first time in our geographic area that adult females show a significantly higher DOB compared to males (p=0,008). Whether this effect may be due to hormonal differences, able to influence gastric emptying, bacterial load, or even the production of urease by H. pylori, merits further investigation.

Aim: The modality of anticancer drug combinations needs to be renovated from empirical into technical-supportive systems. Methods: To challenge past therapeutic routines, the new landscape may be established. Among the different areas of anticancer drug combination study, research in the fields of medical study is the most important one-including disciplinary of therapeutics in different cancer stages, modern genetic/ molecular diagnostics, cancer bioinformatics, traditional Chinese medicine, mathematical data analysis, therapeutic toxicity monitor, personalized cancer medicine and so on. Discussion: This article addresses these types of cancer therapeutic management systems for clinical anticancer drug combination utilities. Conclusion: Future cancer drug combinational studies and clinical optimums must be implemented.

Background: Coronary bifurcated lesions (CBL) represent a hot topic of interventional cardiology. Provisional stenting, i.e. implantation of a drug-eluting (DES) in the main branch followed by side-branch (SB) intervention in case of suboptimal SB result, represents the gold standard to treat the vast majority of CBL undergoing percutaneous coronary interventions (PCI). The best technique for bail-out SB stenting has not been established. Prospective randomized trials comparing different stenting techniques may help provide important insights regarding the best way to conduct PCI in patients with CBL. Methods: The recently published Bifurcations Bad Krozingen (BBK) II trial is the last important randomized study in the field of bifurcation PCI and is focused on the search for the best management of those patients with suboptimal SB result during provisional stenting. Two different SB implantation strategies after provisional stenting have been compared. In the present manuscript, we employed BBK II results in the context of available literature highlighting important specific features of the study with main emphasis on patient selection process and techniques applied.

Background: Neo-adjuvant chemotherapy (NAC) can facilitate breast conservation, allows in vivo testing of chemotherapy sensitivity and provides a route to accelerated approval of new therapies. For HER2 positive breast cancer, the anti-HER2 monoclonal antibody, trastuzumab, is a standard component of neo-adjuvant therapy. Pertuzumab is an anti-HER2 monoclonal antibody with a distinct binding site to trastuzumab, which prevents HER2 receptor dimerisation. In early breast cancer, the addition of pertuzumab to docetaxel and trastuzumab resulted in a higher rate of pathological complete response (pCR), leading to accelerated approval in many territories. T-DM1 is a novel antibody-drug conjugate, combining trastuzumab with a potent cytotoxic, DM1, a maytansine derivative, via a stable thioether linker. In advanced breast cancer (ABC), T-DM1 improves survival compared to standard 2nd or 3rd line regimens, but not compared to first line chemotherapy plus trastuzumab. The KRISTINE trial investigated the combination of T-DM1 with pertuzumab compared to standard chemotherapy plus trastuzumab and pertuzumab in early breast cancer. Methods: This review summarises the data supporting current standards in the neo-adjuvant treatment of HER2 positive early breast cancer and the impact of the KRISTINE trial results. Results: T-DM1 with pertuzumab did not improve pCR over standard therapy, although the novel combination was better tolerated, and a sub-group of patients (44%) achieved pCR with the systemic chemotherapy-free regimen. This suggests that not all HER2 positive early breast cancer patients require systemic chemotherapy and provides the potential, if these patients can be identified up-front, to de-escalate therapy. Conclusion: Although the KRISTINE trial results have not changed the standard of care for the neoadjuvant management of HER2 positive breast cancer, further research is needed to determine whether T-DM1 could be used to de-escalate NAC for selected patients.