Clomiphene citrate plus letrozole versus clomiphene citrate alone for ovulation induction in infertile women with chronic anovulation: A randomized controlled trial

Objective To compare the efficacy of combination clomiphene citrate (CC) plus letrozole with that of CC alone for ovulation induction in infertile women with chronic anovulation. Material and methods This randomized controlled trial was conducted at the Infertility and Reproductive Biology Unit of the Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the August 2020-September 2021 study period. Anovulatory women aged 18-40 years were equally allocated into either the CC 50 mg plus letrozole 2.5 mg once daily group or the CC 50 mg once daily group. The study drugs were administered on days 3-7 of each study patient’s menstrual cycle. The primary outcome was the ovulation rate defined by serum progesterone >3 ng/mL at mid-luteal phase. The secondary outcomes were menstrual cycle characteristics, endometrial thickness, conception rate, and adverse events. Results One hundred women (50 per group) were enrolled. The mean age and prevalence of polycystic ovary syndrome were non-significantly different between groups. The ovulation rate according to intention-to-treat analysis was 78% and 70% in the combination and CC alone groups, respectively (p>0.05). There was no significant difference between groups for either mean endometrial thickness or number of dominant follicles. No serious adverse events were observed in either group. Conclusion There was no significant difference between combination CC plus letrozole and CC alone relative to their ability to induce ovulation in infertile women with chronic anovulation. The small number of live births (1 per group) was too low to be statistically analyzed.

QOLP-03. OBSERVATIONS OF COMPLEMENTARY CANNABIS THERAPY IN MALIGNANT GLIOMA PATIENTS

INTRODUCTION As of 5/15/2021, medical marijuana programs exist in 37 states, and marijuana is legal for recreational use in 17 states. In Connecticut, the CT Medical Marijuana Program (MMP) was created in 2012 and I began certifying my patients with malignant glioma (brain cancer) for the program in 2014. I now provide data on my experience with complementary cannabis therapy. PART 1 Between 9/1/2014 and 6/1/2018, 23 patients with malignant glioma were registered in the CT MMP and received a card. Of these 23 patients, 15 patients took a daily cannabis oil supplement for at least 6 months during their treatment, and 7 patients used cannabis products only as needed. 3 patients are still alive, all in the daily cannabis oil group (41, 54 and 77 months). The median overall survival in the daily group was 22.0 months, versus 16.9 months in the as needed group. PART 2 Since 9/1/2014, 71 patients with malignant glioma were certified for the CT MMP. Of these 71 patients, 15 did not complete the patient registration process and did not receive a card for the MMP. As of 5/15/2021, of the 56 registered patients, there are 20 Active patients and 36 Inactive patients. Regarding the Inactive patients, 29 have died and 7 are alive but did not renew their card. Amongst Active patients, 4 are currently taking a daily cannabis oil supplement as a complementary therapy, and 16 are currently using cannabis products only as needed for symptoms. The 4 patients employing complementary therapy currently have a survival of 8, 31, 33, and 35 months. CONCLUSION In my experience, complementary cannabis treatment is well tolerated in malignant glioma patients, and can provide significant palliative benefit to treat insomnia and nausea. Serious adverse events attributed to cannabis products, or decreased survival, have not been observed.

Tamsulosin, versus Tamsulosin in combination with Solifenacin versus Tamsulosin in combination with Trospium chloride for treatment of Double-J stent-related symptoms

Background Stenting has been primarily used to treat urinary obstruction and the frequency of this use is increasing with the increase in ureteroscopic management. In cases of acute obstruction, a stent is used temporarily to stabilize the patient until definitive therapy. The stent is generally placed if there is accompanying ureteric injury or in those with a residual stone after ureteroscopic lithotripsy. Placing a ureteric stent after ureteroscopy with stone extraction is done by some urologists routinely to prevent possible stenosis or to decrease secondary pain caused by mucosal oedema. However, routinely placing a stent to prevent late complications or to relieve flank pain from a ureteric stricture or mucosal oedema after surgery is questionable. Stent-related symptoms are quite problem in nearly 80% of patients that has been implicated in short-term morbidities in terms of negative impact on the patients’ quality of life, body pains and hematuria. Various attempts had been made to minimize these symptoms but pharmacological treatment is the simplest and a noninvasive option. Numerous drugs had been tried to relieve these symptoms like alpha blockers, anticholinergics and analgesics. Objective To compare the efficacy of tamsulosin alone, tamsulosin in combination with solifenacin and tamsulosin in combination with trospium chloride in in the relief of Double-J stentrelated symptoms following uncomplicated ureteroscopic lithotripsy (URSL). Patients and Methods The present study was a prospective randomized comparative study conducted on 60 patients whith double-J stent inserted following uncomplicated ureteroscopic lithotripsy (URSL) in Ain Shams University Hospital and Karmouz Hospital over a period of 1 year. The patient were randomized into 3 equal groups (1:1:1 randomization): Group A:20 patients were treated by Tamsulosin (0.4 mg) alone once daily. Group B:20 patients were treated by Tamsulosin (0.4 mg) once daily in combination with Solifenacin (5 mg) once daily. Group C: 20 patients were treated by Tamsulosin (0.4 mg) once daily in combination with Trospium chloride (20 mg) twice daily. All patients were assessed 1 week postoperatively after Double-J stent insertion. Then, the patients were start the medical treatment and were assessed 3 weeks after starting the medical treatment. Results The study shows that the combination of the tamsulosin 0.4 mg/day and trospium chloride 20 mg twice/day are significantly superior to the tamsulosin 0.4 mg once alone / day and the combination of the tamsulosin 0.4 mg /day and the solifenacine 5 mg /day for the treatment of the LUTS in d.j stent cases except in the frecuncy the combination of tamsulosin 0.4 mg/day and the solifenacine 5 mg/day are signicantly superior. Also, the drugs are safe with mild few side effects. There were no significant differences regarding headache, dizziness, backache, myalgia and orthostatic hypotension. Conclusion The study show that the combination of the tamsulosin 0.4 mg/day and the trospium chloride 20 mg twice /day are significantly superior to the tamsulosin 0.4 mg once alone / day and the combination of the tamsulosin 0.4 mg /day and the solifenacine 5 mg /day for the treatment of the LUTS in d.j stent cases except in the frecuncy the combination of tamsulosin 0.4 mg/day and the solifenacine 5 mg/day are signicantly superior.

Effects of silodosin, darifenacin, and combination therapy for the treatment of ureteral stent related discomforts

Background: To evaluate the effect of silodosin, darifenacin and combination therapy of two agents in improving the lower urinary tract symptoms of patients with indwelling double-J ureteral stents.Methods: A total of 150 patients underwent placement of a double-J ureteral stent after retrograde ureteroscopy for urinary stone disease. All patients received polyurethane double-J ureteral stents (4 Fr and length 26 cm), which were removed at a mean of around 14 days postoperatively. A total of 40 patients were given no medication (group 1), 39 patients were given silodosin 4 mg once daily (group 2), 40 patients were given darifenacin 7.5 mg once daily (group 3), and 31 patients were given a combination of two agents postoperatively (group 4). International prostate symptom score (IPSS) and visual analogue pain scale (VAPS) questionnaires were completed by each patient at 1st day postoperatively and on the day of stent removal.Results: In the total group of patients, the mean age was 50.24±12.90 years. There was a significant difference in the IPSS total score between group 1 and groups 3 and 4. Group 4 also differed significantly from group 1 in the irritative subscore. The obstructive subscore differed between groups 2 and 4 and group 1. There was a statistically significant difference between group 1 and group 4 in the quality of life (QoL) score.Conclusions: Combination therapy with silodosin and darifenacin improved both irritative and obstructive symptoms more than in the other groups. Combination therapy should be strongly considered for patients who complain of stent-related symptoms.

Daily and Weekly Iron Supplementations to Improve Iron Status in Infants: A Randomized Controlled Trial

Background: Iron deficiency anemia screening and iron supplementation in infants aged 6 to12 months are recommended in the Guideline in Child Health Supervision. Objective: To evaluate the effectiveness of weekly iron supplementation compared with daily supplementation in improving the iron status in infants. Materials and Methods: A single-blind randomized controlled trial was conducted in infants aged 6 months visiting the Well Child Clinic between May 2019 and November 2020 at Burapha University Hospital, Chonburi, Thailand. The intervention consisted of either daily or weekly iron supplementation combined with iron-rich complementary food promotion for six months. The outcomes were the differences of serum ferritin and hematological variables before and after being iron supplemented. Results: Sixty-nine of the six-month-old healthy infants were randomized to receive either 10 mg Fe/day as the daily group or 30 mg Fe/week as the weekly group. Forty-five infants with 24 in the daily group and 21 in the weekly group completed the intervention. After the six-month period of iron supplementation, the average differences of serum ferritin in the daily and the weekly group were 10.85 (–13.19, 34.49) and –9.31 (–23.86, –2.30) ng/mL, respectively (p=0.012). The average differences of hemoglobin in the daily and the weekly group were 0.58±0.82 and 0.08±0.59 g/dL, respectively (95% CI 0.06 to 0.93; p=0.026). Conclusion: Daily iron supplementation of 10 mg/day is more effective than 30 mg weekly iron supplementation in improving iron status and hemoglobin level in the Thai infants. Keywords: Anemia; Ferritin; Infants; Iron deficiency; Iron supplementation

A Randomized Controlled Trial of Daily and Weekly Iron Supplementations for Improving Iron Status in the Infants

Background: Iron deficiency anemia screening and iron supplementation in infants aged 6-12 months are recommended in the Guideline in Child Health Supervision. This study aims to evaluate the effectiveness of weekly iron supplementation compared with daily supplementation in improving the iron status in infants.Methods: A single-blind randomized controlled trial was conducted in infants aged 6 months visiting the Well Child Clinic between May 2019 and November 2020 at Burapha University Hospital, Chonburi, Thailand. The intervention consisted of either daily or weekly iron supplementation combined with iron-rich complementary food promotion for six months. The outcomes were the differences of serum ferritin and hematological variables before and after being iron supplemented. Results: Sixty-nine six-month-old healthy infants were randomized to receive either 10 mg Fe/day (daily group) or 30 mg Fe/week (weekly group). Forty-five infants (daily group; n = 24 and weekly group; n = 21) completed the intervention. After the six-month period of iron supplementation, the mean differences of serum ferritin in the daily and the weekly group were 8.78±37.21 and -13.05 ±17.53 ng/mL, respectively (95%CI: 4.54, 39.12; P=0.015). The mean differences of hemoglobin in the daily and the weekly group were 0.58±0.82 and 0.08±0.59 g/dL, respectively (95%CI: 0.06, 0.93; P=0.026). Daily supplementation could prevent iron deficiency more than weekly supplementation significantly (P=0.029), particularly in the exclusive breastfeeding subgroup (P=0.032).Conclusions: Daily iron supplementation is more effective than weekly iron supplementation in improving iron status and hemoglobin level in infants, especially in the exclusively breast-feds.Trial registration: TCTR20191107001, November 7th, 2019. Retrospectively registered, http://www.thaiclinicaltrials.org

Chronic Treatment of Ascorbic Acid Leads to Age-Dependent Neuroprotection against Oxidative Injury in Hippocampal Slice Cultures

Increased oxidative damage in the brain, which increases with age, is the cause of abnormal brain function and various diseases. Ascorbic acid (AA) is known as an endogenous antioxidant that provides neuronal protection against oxidative damage. However, with aging, its extracellular concentrations and uptake decrease in the brain. Few studies have dealt with age-related functional changes in the brain to sustained ascorbate supplementation. This study aimed to investigate the susceptibility of hippocampal neurons to oxidative injury following acute and chronic AA administration. Oxidative stress was induced by kainic acid (KA, 5 µM) for 18 h in hippocampal slice cultures. After KA exposure, less neuronal cell death was observed in the 3 w cultured slice compared to the 9 w cultured slice. In the chronic AA treatment (6 w), the 9 w-daily group showed reduced neuronal cell death and increased superoxide dismutase (SOD) and Nrf2 expressions compared to the 9 w. In addition, the 9 w group showed delayed latencies and reduced signal activity compared to the 3 w, while the 9 w-daily group showed shorter latencies and increased signal activity than the 9 w. These results suggest that the maintenance of the antioxidant system by chronic AA treatment during aging could preserve redox capacity to protect hippocampal neurons from age-related oxidative stress.

Clinical efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation in real-world clinical practice

Aim: to assess the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AFib) in real-world clinical practice. Patients and Methods: this non-interventional prospective study enrolled 356 patients aged 50-75 years with AFib and creatinine clearance ≥50 ml/min. All patients were divided into three age-matched groups based on DOACs prescribed. Group 1 patients (n=120) received rivaroxaban 20 mg daily. Group 2 patients (n=112) received dabigatran etexilate 150 mg twice daily. Group 3 patients (n=124) received apixaban 5 mg twice daily. The groups were comparable in comorbidities and the risks of thrombotic and hemorrhagic complications. Followup was 2 years after starting treatment. Thrombotic complications, massive bleedings, and death for any reason were considered end-points. Results: no significant differences in the rate of cardiogenic thrombotic complications between the groups were reported. In patients who received apixaban, fewer bleeding complications were diagnosed (insignificant differences). Conclusions: the efficacy and safety of DOACs in patients over 50 years are similar. KEYWORDS: atrial fibrillation, oral anticoagulants, thrombotic complications, infarction, stroke, bleedings. FOR CITATION: Khruslov M.V., Sorokina A.S., Sapel'nikova Yu.A., Vavilova T.V. Clinical efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation in real-world clinical practice. Russian Medical Inquiry. 2021;5(4):196–199 (in Russ.). DOI: 10.32364/2587-6821-2021-5-4-196-199.

Creative Thinking Techniques

This chapter suggests how to facilitate group learning by creative thinking techniques in PBL. Techniques of brainstorming, checklist, and mind mapping are usually used among students in daily group experience. Using techniques can be reflected by the knowledge conversation model introduced in Chapter 5. Then a case will be discussed on a 5-day creativity training program carried out in Medialogy education at Aalborg University in Denmark. The case brings implications for Chinese universities: ‘fun' as a key to creativity training, mediation between individual and collective work, increasing creativity as an identity, and inquires of a long-term effort.

Daily Versus Weekly Iron and Folic Acid Supplementation Regimen- A Randomized Parallel Open Label Trial among Reproductive Age Group Women in an Urban Poor Locality of Bengaluru

Introduction:The global prevalence of anaemia in non-pregnant women is 30.2% and in India it is 56.2%.At least half the burden of anaemia is associated with iron deficiency. Women of reproductive age are at higher risk of developing iron deficiency because of losses during menstruation. Though Daily supplementation with iron and folic acid for a period of 3 months has been the standard as an approach for the prevention and treatment of iron deficiency anaemia among women of reproductive age, there has been limited success with the daily regimen in public health programmes, Intermittent use of oral iron supplements has been proposed as an effective alternative. Objectives: To compare the effectiveness of weekly and daily oral iron and folic acid therapy in improving the Hemoglobin levels among the reproductive age group women, adverse effects and compliance to both the regimens. Method:This was a comparative Randomized parallel open label trial conducted in an urban poor locality of Bengaluru conducted between January 2014 and January 2016. All the women in the reproductive age group (15-45 years) with mild to moderate anemia were included in the study. Sample size of 106 subjects was randomly allocated into the 2 groups (53 into weekly regimen and 53 into daily regimen). The subjects were supplemented with IFA tablets for 3 months according to their regimen. Results:Mean increase in Haemoglobin (Hb) in the daily group (1.92±1.1 g/dl) was significantly (P=<0.01) more when compared to that in the weekly group (0.91±0.82 g/dl). Incidence of all the Adverse Drug Reactions (ADRs) were more in the daily group compared to weekly group. However, the difference was only significant for abdominal pain and metallic taste (P=<0.01 and 0.02 respectively). The proportion of subjects reporting at least one ADR was also significantly more (P=<0.01) in the daily group compared to the weekly group. Compliance for weekly regimen (97.12%) was found to be significantly better(P=<0.01) when compared to that of the daily regimen (94.07%). Conclusions: Daily regimen was more effective in raising the hemoglobin levels when compared to weekly regimen. Incidence of abdominal pain and metallic taste were significantly more in the daily group compared to weekly group. Compliance for weekly regimen was significantly better when compared to that of the daily regimen.