Prospective Placebo-controlled Study Research Articles

1566-P: Growth Hormone Replacement Treatment Improves Nonalcoholic Fatty Liver Disease in Patients with Pituitary Stalk Interruption Syndrome—A Randomized, Single-Blind, Placebo-Controlled Prospective Cohort Study

1566-P: Growth Hormone Replacement Treatment Improves Nonalcoholic Fatty Liver Disease in Patients with Pituitary Stalk Interruption Syndrome—A Randomized, Single-Blind, Placebo-Controlled Prospective Cohort Study

(029) Safety and Efficacy of Botulinum Neurotoxin in the Treatment of Erectile Dysfunction Refractory to Phosphodiesterase Inhibitors: Results of a Randomized Controlled Trial

Abstract Introduction There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation. Objective To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). Methods A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&3 (SEP-2&3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT-A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&Q2) were completed at 2-, 6-, and 12-weeks post treatment. Results Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p < 0.001) compared to the control group. At 6- and 12-weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP-2, and GAQ-Q1&Q2 positive responders compared to the control group. At 6 weeks, where there was a 5-point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group. Conclusions BoNT-A is safe and effective as a potential treatment for ED refractory to PDE5I therapy. Disclosure No.

Intravaginal exposure to seminal plasma after ovum pick-up does not increase live birth rates after in vitro fertilization or intracytoplasmic sperm injection treatment: a double-blind, placebo-controlled randomized trial

ObjectiveIt has been suggested that intravaginal deposition of seminal plasma after ovum pick up for in vitro fertilization, IVF, increases pregnancy and live birth rates. Thus, the present study aimed to detect whether intravaginal exposure to prepared seminal plasma led to an absolute increase in live birth rate after IVF by 10 % compared to placebo. DesignDouble-blind, placebo-controlled prospective study. Outcome assessment was made before the type of intervention was unblinded. The outcome data were analyzed according to an intention-to-treat protocol. SubjectsCouples scheduled for an IVF treatment cycle, in total 792 couples (393 in the seminal plasma group and 399 in the control group) were recruited over a five-year period of inclusion in a single-center setting. InterventionOn the day of ovum pick up the couples were randomized to groups receiving either vaginal deposition of prepared seminal plasma from the partner or to saline. Both participants and physician were blind to the grouping. Main Outcome MeasuresThe primary outcome was live birth. The secondary outcomes were a positive pregnancy test, defined as human chorionic gonadotropin identified in urine three weeks after ovum pick up, and clinical pregnancy, defined as an intrauterine viable pregnancy assessed by transvaginal sonography after five to seven weeks. ResultsIn the index group, 35.4 % had a positive pregnancy test (RR 0.93, 95% CI 0.78-1.10), 28.8 % had a clinical pregnancy (RR 1.00, 95% CI 0.97-1.03) and 26.5 % had a live birth (RR 0.86, 95% CI 0.70-1.07), adjusted for day of transfer, female age and number of fertilized oocytes. Corresponding rates in the control group were 37.3 %, 33.6 % and 29.8 %. No statistically significant differences regarding outcomes between the two intervention groups were found. ConclusionPrepared seminal plasma applied in the vagina directly after ovum pick-up did not increase the rates of live birth or clinical pregnancies. The importance of immunological factors to allow the implantation of an embryo is not questioned, but no improvement in the live birth rates in IVF treatment by introducing the male partner´s prepared seminal plasma after ovum pick-up could be found.

The efficacy of N-acetylcysteine in decreasing airway inflammation and mucus accumulation in horses with 18 hours of head confinement.

During transportation many horses develop post-transportation infection, which can be life-threatening and end their sport career. Preventing mucus accumulation and inflammation during transportation is vital, emphasizing the need for effective strategies to enhance overall horse health welfare. Assess the impact of N-acetylcysteine (NAC) on mucus accumulation and inflammation in horses subjected to 18 hours of head confinement. Six healthy crossbred horses, 5.3 ± 2.1 years of age and weighing 387 ± 30 kg. Prospective placebo-controlled cross-over design study. The horses' heads were restrained in their stalls for a period of 18 hours. They were studied under 4 conditions: Not confined (NC): before head confinement, placebo (P), and confined head (CH): 18 hours of head confinement without treatment, and N-Acetylcysteine (NAC): 18 hours of head confinement treated with NAC before confinement (15 mg/kg/day NAC PO for 3 days). Bronchoalveolar lavage (BAL) was performed in each condition. Mucus accumulation along the trachea was evaluated by endoscopy. Endoscopic scores were significantly different between CH and other conditions, whereas no significant differences were found among NC, P, and NAC. The BAL cell count (34 291 ± 2624 cells/μL), neutrophil and lymphocyte count (18 601 ± 3193 cells/μL and 3337.4 ± 593 cells/μL, respectively) in CH were significantly higher compared to NAC. Neutrophil percentage was significantly higher in CH (53.8 ± 8%) compared to horses that received NAC (20.08 ± 8%). Conversely, in comparison to NAC (66.33 ± 9%), the percentage of macrophages was significantly lower in CH (35.7 ± 10%). N-acetylcysteine was found to significantly decrease mucus accumulation and inflammatory cell counts in horses with head confinement.

Treatment of refractory hematospermia with Finasteride: A prospective placebo-controlled study

Background: Finasteride is being used to treat recurrent hematuria due to BPH. Androgen has an essential role in the production of angiogenic factors such as VEGF. Vessel density & VEGF decreases after finasteride treatment and thus improve haematospermia. Objective: To test the efficacy of finasteride to control refractory idiopathic hematospermia for which conservative treatment has failed. Methodology: This Prospective placebo-controlled study was carried out from July 2019 to June 2022 with 48 patients of hematospermia presented to the outpatient department of NIKDU. Twenty-two patients had refractory hematospermia of idiopathic nature. They were randomized into two equal groups, 11 patients in each group. One group received 5 mg finasteride daily for 3 months, and the other group received placebo. Patients were followed up with semen analysis and TRUS for 3 consecutive months and after 1 year. Result: In the finasteride-treated group, remission of hematospermia occurred in 5 patients (45%) within 1 month. Patients continued treatment for 3 months without the recurrence of hematospermia. After stopping finasteride treatment, hematospermia recurred in 3 out of 9 patients 12 months later. Two cases were not improved, but a significant decrease in frequency & amount of bleeding was observed in semen analysis. In the placebo-treated group, cessation of hematospermia occurred in 3 cases (27%) versus 9 (81%) in the finasteride group (P = 0.03) after 3 months of treatment. Conclusion: Three months of treatment with finasteride for refractory idiopathic hematospermia significantly cures hematospermia with no undesirable side effects. Bangladesh J. Urol. 2022; 25(1): 33-66

Phase I/II randomized, double-masked, placebo-controlled study of processed amniotic fluid drops after PRK.

To evaluate the safety and efficacy of processed amniotic fluid (pAF) used postoperatively after photorefractive keratectomy (PRK). University of Utah, Moran Eye Center, Salt Lake City, Utah. Randomized, double-masked, placebo-controlled prospective study. 61 participants were randomized to receive either placebo or pAF drops, which were instilled 4 times per day for 1 week after PRK along with routine postoperative medications. The primary outcome measure was time to full re-epithelialization in days. Secondary measures included visual acuity at 30 days and postoperative pain scores during the first week. There was no significant difference in time to re-epithelialization, with a median of 5 days for both groups. There were no difference in pain indicator scores during the first week and no difference in corneal staining scores at day 30 between the 2 groups. There were no adverse events. This pilot study evaluating the safety and efficacy of pAF as an additional postoperative topical medication for PRK demonstrated that pAF did not improve the rate of epithelial healing after PRK. pAF may be safely studied in other ocular conditions to determine its effect on epithelial healing.

Acetazolamide, Short Bed Rest, and Subfascial Off-Suction Drainage in Preventing Persistent Spinal Fluid Leaks from Incidental Dural Tears.

Postoperative cerebrospinal fluid (CSF) leak might occur after the repair of dural tears. Acetazolamide lowers intradural pressure by decreasing CSF production. The aim of this study was to investigate the incidence of persistent CSF leak from incidental dural tears after using acetazolamide, short bed rest, and subfascial off-suction drainage. The medical records at the Ain Shams University hospital were examined retrospectively for this descriptive single-arm cohort study. Adult patients who underwent lumbar degenerative spine surgery from January 2011 through January 2021 were enrolled. The included patients experienced a CSF leak and were administered acetazolamide 1.5 g/d from postoperative day (POD) 1 to POD 7. Subfascial drainage was kept for a maximum of 5 days without suction. Seventy-four patients met the inclusion criteria of the study. Fifty-nine patients (79.7%) had recurrent lumbar surgery. The average age of the patients was 55.7 years. In all patients, the quantity of fluid in the drain decreased on a daily basis. The subfascial drain was kept for 5 days in 26 patients (35.1%). There was no wound infection, collection, or persistent CSF leakage in any of the patients over the 6-month follow-up period. In this study, acetazolamide was well tolerated by the patients and, in addition to short bed rest (72 hours) and off-suction subfascial drainage, did not result in persistent CSF leakage in any patient. A prospective placebo-controlled study is beneficial to confirm the efficacy of acetazolamide in preventing CSF leakage.

Evaluation of efficacy and safety of intraoperative tranexamic acid: prospective placebo-controlled comparative study

ABSTRACT Objectives Evaluation of the effect and safety of intravenous and local application of tranexamic acid (TXA) on outcomes of transurethral resection of the prostate (TURP). Patients & Methods 138 patients were divided into three groups according to the mode of TXA delivery (Groups I and II) or placebo. Hemoglobin concentration (HBC) and hematocrit value (HTC) were determined before and immediately after surgery to calculate hemoglobin deficit and estimated intraoperative blood loss (IO-BL). All surgeries were performed under bupivacaine spinal anesthesia with the preoperative saline co-load infusion. Results: Patients who received combined IV and local delivery of TXA showed significantly shorter operative time and duration of PO catheterization and hospital stay than patients of other groups. The IO-BL was significantly lower in patients received TXA than placebo. Hemoglobin deficit after surgery was significantly lower in patients received both IV and local delivery of TXA than patients of other groups. No adverse effects of TXA s were reported. Conclusion The applied policy for antifibrinolysis during TURP was safe and effectively improved operative and immediate PO outcomes.

Commentary: Dexamethasone and dilemma

Postoperative endophthalmitis has always been a nightmare for the patients and surgeons alike. Around 90% of patients having post trabeculectomy endophthalmitis and 40% of patients having postcataract surgery endophthalmitis would end up having final visual acuity worse than 20/200.[1] The economic burden of endophthalmitis is also significant as stated by Schmier et al.;[2] the average adjusted ophthalmic reimbursements were 156% greater for cases that developed endophthalmitis than for subjects having uncomplicated cataract surgery. The psychological impact on quality of life is also significant leading to poorer psychological well-being and ability to maintain a role in daily life.[3] Even after decades of publishing, the endophthalmitis vitrectomy study (EVS)[4] still holds key role in the endophthalmitis management algorithms. Ho et al.[5] in their study suggested that early vitrectomy may be beneficial for all cases and not just the ones with light perception or worse visual acuity as stated in EVS.[4] Few other studies also favor early vitrectomy.[67] The notable fact that EVS includes only postcataract surgery cases makes its significance diluted in cases post procedures other than cataract surgery specially in current era of variety of intravitreal injections, newer and more advanced surgical techniques, and newer drugs. Additionally, the postcataract endophthalmitis was proven to have better visual outcome than post trabeculectomy, postintravitreal injection, and endogenous endophthalmitis.[5] In treating endophthalmitis, antibiotics are the mainstay. Their augmentation with steroids remains controversial as ever. Many studies have reported that steroids do not add additional benefit to the final visual acuity of the patients.[8] The time of starting of steroids remains in the uncertainty. Concerns have been expressed regarding their safety and long-term outcomes. Shah et al.[9] reported worse visual outcome with the use of intravitreal steroids. In contrary to these reports, multiple studies have reported favorable outcomes with the use of intravitreal steroids and some reported that with the use of steroids even though the visual acuity did not have benefit, the intraocular inflammation and the overall morbidity related to the condition were helped.[101112] Albrecht et al.[11] in their study analyzed groups of “postcataract surgery,” “bleb related,” and “other” endophthalmitis, and they found a clinical trend of better visual acuity in the subgroup of postcataract surgery endophthalmitis patients who received steroids. Gan et al.[12] found out in their prospective placebo-controlled study that there was a trend toward better visual outcome in patients with suspected bacterial endophthalmitis when treatment with intravitreal antibiotics was combined with intravitreal dexamethasone. Multiple animal studies have also found out intraocular steroids to be beneficial in endophthalmitis.[81314] The authors in their practice have also noticed that during vitrectomy, immediate KOH mount assessment in a standard lab to rule out fungal infection and adjuvant intravitreal dexamethasone has helped their patients with faster recovery and less inflammation. The current metaanalysis does not show any clear visual benefit from use of adjuvant intravitreal dexamethasone in bacterial endophthalmitis.[15] Prospective randomized controlled trials for the treatment of postprocedure endophthalmitis with multicenter involvement are needed to clarify the gray areas around the usage of steroids and formulating preferred practice patterns for the new era.

A split-face, blind, randomized placebo-controlled clinical trial investigating the efficacy and safety of hyaluronic acid filler for the correction of atrophic facial scars.

Hyaluronic acid fillers have been studied extensively for facial wrinkles; however, their efficacy for atrophic facial scars has yet to be analyzed in a prospective placebo-controlled study. To analyze the efficacy and safety of a hyaluronic acid filler for atrophic facial scars. Fifteen subjects were randomized to receive up to 1 ml of VYC-17.5L on one cheek and up to 1ml of saline on the other side, with an optional touch-up treatment. Subjects were graded by a live blind evaluator using the Quantitative Global Scarring Grading System (QGSGS) (J Cosmet Dermatol. 2006;5:48), the Global Aesthetic Improvement Scale (GAIS), and Canfield photo-analysis. According to the blind evaluator, there was a significant reduction 90 days after the last treatment on the QGSGS for VYC-17.5L compared with saline (-6.6 VYC-17.5L vs -1.7 saline [t(28)=-4.3196, p= 0.008]). There was a smaller, but still significant reduction on the QGSGS for saline alone (10.4 to 8.6 [t(14)=-3.453, p= 0.004]). In addition, 93% (13/14) of subjects chose VYC-17.5L over saline treatment and reported an improvement on the GAIS. There were no serious side effects and all minor side effects resolved by Day 30. VYC-17.5L achieved significant improvements in rolling atrophic scars as compared to saline, though saline also had modest improvements.

Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients

Background and objectivePaclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer.Patients and methodsThis randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann–Whitney U test, and chi-square test.ResultsAs compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9th and 12th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo.ConclusionAlpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer.Trial registrationClinicalTrials.gov: NCT03908528.

Efficacy of 0.01% low dose atropine and its correlation with various factors in myopia control in the Indian population

We aimed to evaluate the efficacy and safety of low-dose atropine compared to placebo in the Indian population and also to study the impact of various modifiable and non-modifiable factors on myopia progression (MP) and drug efficacy (DE). It was a single-centre prospective placebo-controlled interventional study. 43 participants aged 6–16 years with progressive myopia received 0.01% atropine in the right eyes (treatment) and placebo in the left eyes (control) for 1-year. The main outcome measures were annual MP and axial length elongation (ALE) in treatment and control eyes and their percentage difference between two eyes (drug efficacy). Secondary outcome measures were the occurrence of any adverse events and the correlation of MP, ALE, and DE with various factors. 40 participants (80 eyes) completed the follow-up. After 1-year, MP was 0.25 D (IQR 0.13–0.44) and 0.69 D (IQR 0.50–1.0) (p < 0.001) in treatment and control respectively (63.89% reduction) with respective ALE of 0.14 mm (IQR 0.05–0.35) and 0.32 mm (IQR 0.19–0.46) (p < 0.001) (44.44% reduction). No adverse events were noted. Reduction in MP and ALE was statistically significant in all children irrespective of age-group, baseline MP, family history, screen-time, near and outdoor-time. The strongest determinants of annual MP were age (Treatment: r = − 0.418, p = 0.007; Control: r = − 0.452, p = 0.003) and baseline MP (Treatment: r = 0.64, p = 0.000; Control: r = 0.79, p = 0.000). Screen-time in control eyes was associated with greater ALE (r = 0.620, p = 0.042). DE was higher when outdoor time exceeded 2 h/day (p = 0.035) while the efficacy was lower with prolonged near activities (p = 0.03), baseline fast-progressors (p < 0.05) and history of parental myopia (p < 0.05). 0.01% atropine is effective and safe in retarding MP and ALE in Indian eyes.

A phase I clinical trial to evaluate the safety of thymoquinone-rich black cumin oil (BlaQmax®) on healthy subjects: Randomized, double-blinded, placebo-controlled prospective study

Black cumin or black seed (Nigella sativa L.) is a popular medicinal herb and culinary spice belonging to Ranunculacea family. Thymoquinone (TQ) is the major active phytoconstituent in black cumin and is abundant in the volatile oil fraction. Though black cumin oil containing low TQ content (less than 1%) has been clinically investigated, clinical efficacy and safety data of TQ-rich oil is limited. A recent study with black cumin oil formulation containing 5% TQ (BCO-5) exhibited significant clinical efficacy to alleviate sleep disorders and stress. So, the present phase 1 randomized, double-blinded, placebo-controlled trial evaluated the safety of BCO-5 at a dose of 200 mg/adult/day for 90 days on healthy subjects (n = 70). Both the biochemical and hematological parameters were analysed along with the adverse events or side effects to establish the clinical safety of BCO-5. The study reported neither serious adverse side effects nor any significant alterations in the hematological parameters. The absence of significant changes in the biochemical parameters related to liver function (ALT, AST, ALP), renal function (serum creatinine and urea) were also observed. However, analysis of lipid profile showed a significant (P < 0.05) reduction in total cholesterol, LDL, VLDL and triglycerides, but within the normal range. In conclusion, BCO-5 is safe at 200 mg/adult/day for human consumption and may be clinically evaluated for various health beneficial pharmacological activities where black cumin oil has been shown to have positive effects.

Şok Dalga Litotripsi Uygulanan Hastalarda İnhaler Aromaterapinin Ağrı ve Anksiyete Üzerine Etkisi

Aim: The aim of this study was to determine the effects of inhaler aromatherapy on pain and anxiety during the shock wave lithotripsy (SWL) protocol. Material and Methods: This placebo-controlled prospective double-blind study included 120 patients who were scheduled to undergo SWL. Patients were randomly assigned a control placebo group 1 (n=40), the lavender group 2 (n=40), and the frankincense group 3 (n=40). The nebulizer (a rate of 2%) was prepared and operated on in the SWL room before the procedure. Data were collected using the visual analog scale (VAS) and the state-trait anxiety inventory (STAI-I). Results: Of the 120 patients included in the study, 67 (55.8%) were male and 53 (44.2%) were female. The mean age of the patients was 37.38±11.35 years. The mean stone size was 11.07±3.09 mm. There were no statistically significant difference between the groups in terms of VAS scores of the patients after the procedure (p=0.557). While there was no statistically significant change in the STAI-I score in group 1 and group 2 after the procedure compared to the pre-procedure, a statistically significant decrease was detected in group 3 (p=0.030). The percentages of patients with changing STAI-I scores were compared, it was observed that the decrease in STAI-I score in group 2 and group 3 at a higher rate compared to group 1 (p=0.018). Conclusion: Frankincense reduced anxiety more significantly than lavender. Both had no significant effect on pain. Inhaler aromatherapy can be used in the SWL process to reduce anxiety and improve treatment compliance.

Safety and efficacy of botulinum neurotoxin in the treatment of erectile dysfunction refractory to phosphodiesterase inhibitors: Results of a randomized controlled trial

There has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation. To evaluate the safety and efficacy of intracavernosal BoNT-A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is). A double-blind randomized placebo-controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&3 (SEP-2&3) questionnaires. Treatment group (n=35) received a single ICI of 100 units of BoNT-A in 2ml of saline and control group (n=35) received a single ICI of 2ml of saline. EHS, PSV, and EDV were assessed at 2weeks post treatment. SHIM, SEP-2, SEP-3, and global assessment questionnaire (GAQ-Q1&Q2) were completed at 2-, 6-, and 12-weeks post treatment. Two weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ-Q1 positive responders (p<0.001) compared to the control group. At 6- and 12-weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP-2, and GAQ-Q1&Q2 positive responders compared to the control group. At 6weeks, where there was a 5-point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group. BoNT-A is safe and effective as a potential treatment for ED refractory to PDE5I therapy.

Efficacy of metformin for treatment and prevention of antipsychotic-induced overweight and obesity in women: an open-label, randomized, prospective placebo-controlled study

Background:The prevalence of obesity and metabolic abnormalities is increased patients with mental disorders receiving psychopharmacotherapy, which significantly impairs their treatment adherence.Aims:To evaluate the efficacy and safety of metformin in prevention and treatment obesity and overweight in patients with mental disorders receiving antipsychotics.Materials and methods: This was an open-label, prospective, randomized, placebo-controlled study of female patients with mental disorders (age, 18 to 50). The patients were randomized into two groups in a 2:1 ratio: the treatment group received metformin and the control group received placebo. Metformin was administered at a starting dose of 500 mg daily, with subsequent up-titration every 2 weeks when necessary, up to 2000 mg daily. The treatment duration was 6 months.Results:Baseline BMI in the treatment group (N=62) was 27,3 [24,0; 30,4] kg/m2; it decreased to 26,0 [22,5; 30,5] kg/m2, p &lt; 0.0001, Wilсoxon test) after 6 months of treatment. The patients receiving metformin decreased their body weight by 3 [-6; 0] kg, or -4,0 [-8; 0] %. In the placebo group (N=30), the baseline BMI was 27,5 [24,0; 32,0] kg/m2and increased to 28,2 [25,8; 34,0] kg/m2at 6 month (p=0.001, Wilсoxon test), or 3 [1; 6] kg. After 6 months of treatment, the difference in BMI between the metformin and placebo groups was significant (26,0 и 28,2 kg/m2, respectively, р=0,027, Mann-Withney test). Six (6) of 62 patients treated with metformin had side effects and were switched to an equivalent dose of prolonged release metformin, with reduction of side effects in 5 of them.Conclusions:The use of metformin in patients with mental disorders receiving antipsychotics allows for reduction or stabilization of body weight in 80% of cases, with ≥5% decrease of body weight in 44% of patients. It is recommended to start metformin at a dose of 500 mg daily with subsequent up-titration of up to 2000 mg if necessary.

The effects of alendronate on the suppression of bone resorption and the promotion of cartilage formation in the human mosaicplasty donor site: A randomized, double-blind, placebo-controlled prospective study

BackgroundWe previously reported that early alendronate administration accelerated bone formation and improved the quality of repaired cartilage in the donor site in rabbits. To investigate whether alendronate administration has effects in humans similar to those observed in rabbits. MethodsThe study cohort included 35 patients over the age of 12-years old who underwent mosaicplasty without osteoporotic therapy from March 2011 to October 2012. The donor sites were medial or lateral in the patellofemoral joint. Placebo (P) or Bonalon containing 35 mg of alendronate (A) was administered orally every week for 8 weeks. The cohort comprised 15 male and 20 female, including 14 right and 21 left knees. The mean age at the time of surgery was 57.1 years. Bone formation was examined using computer tomography and lateral knee radiography, and cartilage formation was examined using magnetic resonance imaging (MRI), second-look assessment, and intraoperative acoustic evaluation. The clinical outcomes were assessed using the Japanese Orthopaedic Association knee score and visual analog scale (VAS). Bone and cartilage formation in the donor site and clinical outcomes were assessed at 3, 6, and 12 months after mosaicplasty. ResultsThe ratio of TRAP-5b in group A was significantly smaller than that in group P at 2 and 8 weeks after mosaicplasty. The extent of bone formation in the donor sites in group A was significantly greater than that in group P at 3 and 6 months after mosaicplasty. Cartilage formation did not differ significantly between the two groups as determined by MRI, macroscopic assessment, and intraoperative acoustic evaluation. Clinical outcomes did not differ significantly between the two groups, and no negative clinical outcomes were observed. ConclusionEarly alendronate administration accelerated bone formation but not cartilage formation in the mosaicplasty donor site in humans.

On the Prevalence of Autoimmune Disease Markers in a Working Population and its Relationship to Wellness

Background: Autoimmune disease prevalence is rising at an increasing rate. However, little research currently exists on pre-screenings for autoimmunity and early disease management. We propose wellness visits should include an autoimmune disease panel screening for autoantibodies at preclinical and clinical levels.&#x0D; Methods: A working population of individuals without formally diagnosed autoimmune disease underwent company-sponsored wellness visits. Wellness markers such as blood pressure and lipid measurements and an autoantibody panel were obtained during the visits. Participants were offered functional medicine information afterwards.&#x0D; Results: Seventy-eight participants completed the visits. One or more wellness marker “abnormalities” were seen in 97% (76/78) of participants. Each wellness marker’s frequency of abnormality ranged from 13–82% of the participants. Preclinical or clinical autoantibody levels were seen in 53% (41/78) of the “healthy” working population with no previous autoimmune disease diagnoses. Preclinical markers were seen in 21% (16/78)of participants and clinical markers were seen in 32% (25/78) of participants. At least one wellness screening abnormality was seen in 98% (40/41) of participants with positive autoantibody findings. At least 50% of participants with a specific wellness abnormality tested at the higher “clinically” significant autoantibody levels.&#x0D; Conclusion: Preliminary findings from this study suggest that the integration of an autoantibody panel in wellness visits may be beneficial. Individuals may also consider healthier living practices and proactive prevention of autoimmune disease pathogenesis through applications of functional medicine and therapeutic lifestyle change. Clinical marker findings in asymptomatic individuals raises a limitation in the usefulness of such a panel, and further research such as a placebo-controlled prospective cohort study with an intervention trial or serial testing of autoantibody prevalence is needed.

Semaglutide reduces fat accumulation in the tongue of obese women with polycystic ovary syndrome: A randomized, placebo-controlled prospective study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

One Giant Step for Giant Cell Arteritis: Updates in Diagnosis and Treatment.

Purpose of ReviewGiant cell arteritis (GCA), a medium and large vessel vasculitis occurring in the aged, remains a formidable disease, capable of taking both vision and life, through a multitude of vascular complications. Our understanding of the spectrum of its manifestations has grown over the years, to include limb claudication, aortitis, and cardiac disease, in addition to the more classic visual complications resulting from of ischemia to branches of the external and internal carotid arteries. While a clinical presentation of headache, jaw claudication, scalp tenderness, fever and other systemic symptoms and serum markers are together highly suggestive of the disease, diagnosis can be challenging in those cases in which classic symptoms are lacking. The purpose of this review is to update the reader on advances in the diagnosis and treatment of giant cell arteritis and to review our evolving understanding of the immunological mechanism underlying the disease, which have helped guide our search for novel therapies.Recent FindingsThere is increasing evidence supporting the use of Doppler ultrasound, dedicated post-contrast T1-weighted spin echo MRI of the scalp arteries and PET scan, which can together improve our diagnostic accuracy in cases in which temporal artery biopsy is either inconclusive or not feasible. Advances in our understanding of the immunological cascades underlying the disease have helped guide our search for steroid-sparing treatments for the GCA, the most important of which has been the IL-6 receptor antibody inhibitor tocilizumab, which has been shown to reduce cumulative steroid dose in a large multicenter, placebo-controlled prospective study. Other biologic agents, such as abatacept and ustekinumab have shown promise in smaller studies.SummaryGCA is no longer a disease whose diagnosis is based exclusively on temporal artery biopsy and whose complications are prevented solely with the use of corticosteroids. Modern vascular imaging techniques and targeted immunologic therapies are heralding a new era for the disease, in which practitioners will hopefully be able to diagnosis it with greater accuracy and treat it with less ischemic complications and iatrogenic side effects.