Open-label Randomized Clinical Trial Research Articles

Comparison of Intracoronary Epinephrine and Adenosine for No-Reflow in Normotensive Patients With Acute Coronary Syndrome (COAR Trial)

Background:Intracoronary epinephrine has been effectively used in treating refractory no-reflow, but there is a dearth of data on its use as a first-line drug in normotensive patients in comparison to the widely used adenosine.Methods:In this open-labeled randomized clinical trial, 201 patients with no-reflow were randomized 1:1 into intracoronary epinephrine as the treatment group and intracoronary adenosine as the control group and followed for 1 month. The primary end points were improvement in coronary flow, as assessed by TIMI (Thrombolysis in Myocardial Infarction) flow, frame counts, and myocardial blush. Secondary end points were in-hospital and short-term mortality and major adverse cardiac events.Results:In all, 101 patients received intracoronary epinephrine and 100 patients received adenosine. Epinephrine was generally well tolerated with no immediate table death or ventricular fibrillation. No-reflow was more effectively improved with epinephrine with final TIMI III flow (90.1% versus 78%, P=0.019) and final corrected TIMI frame count (24±8.43 versus 26.63±9.22, P=0.036). However, no significant difference was observed in final grade III myocardial blush (55.4% versus 45%, P=0.139), mean reduction of corrected TIMI frame count (−25.71±11.79 versus −26.08±11.71, P=0.825), in-hospital and short-term mortality, and major adverse cardiac events.Conclusions:Epinephrine is relatively safe to use in no-reflow in normotensive patients. A significantly higher frequency of post-treatment TIMI III flow grade and lower final corrected TIMI frame count with relatively better achievement of myocardial blush grade III translate into it displaying relatively better efficacy than adenosine.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04699110.

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels.

BackgroundMetastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma.MethodsThis is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS2, adverse events, quality of life, and financial toxicity.DiscussionThis is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-021-11249-7.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis

In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. ClinicalTrials.gov Identifier: NCT02578069.

Safety of Intraparenchymal Injection of Allogenic Placenta Mesenchymal Stem Cells Derived Exosome in Patients Undergoing Decompressive Craniectomy Following Malignant Middle Cerebral Artery Infarct, A Pilot Randomized Clinical Trial.

Background:Malignant middle cerebral artery infarct (mMCAI) largely contributes to high mortality and physical disability among adults. Surviving individuals may not have proper outcomes and suffer from severe lasting disabilities. Utilization of stem cells and paracrine factor for regenerative purposes is considered as a potential strategy for patients with neurological deficits. While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) reduce post-treatment neurological deficits and prevent disability and also promote recovery, few randomized clinical trials (RCT) have assessed exosome therapy in humans.Methods:In this RCT, we assessed the safety of intraparenchymal injection placenta MSC-derived Exosome in mMCAI patients with average age of 62 years between January, 2019, till September, 2020. The study was done in a single-center as an open-label RCT, with a 3-months follow-up. Primary outcomes assessed the safety and also disability indexes were followed.Results:Five mMCAI patients were included with mean NIHSS: 17.6 ± 5.02. The mean MRS was 3.25 ± 0.95 in three patients. No serious adverse events were observed. Hematoma or local reaction as excessive edema were not seen at the site of injection.Conclusions:Intraparenchymal implantation of MSC-EXO showed no post-interventional adverse effects in five ischemic stroke patients. It is proposed Local injection Exosome treatment following mMCAI can be safe and in future, it would be applied as a supportive, restorative and preventive treatment in patients who suffer from acute ischemic stroke and post ischemic disability.

The efficacy and safety of Tafalgin in patients with cancer pain. Results of an open-label comparative multicenter randomized clinical trial

<h3></h3> Необходимость создания новых безопасных препаратов для адекватного контроля боли у онкологических пациентов очевидна. Одним из направлений является поиск селективных молекул, взаимодействующих с μ1-опиоидными рецепторами, лишенных многих побочных эффектов опиоидов. Такой препарат создан в России — это Тафалгин, при этом он не имеет зарубежных аналогов. <h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Оценить эффективность и безопасность анальгетика Тафалгина у онкологических пациентов с хроническим болевым синдромом (ХБС), подтвердить гипотезу о неменьшей эффективности Тафалгина в сравнении с морфином. <h3>МАТЕРИАЛ И МЕТОДЫ</h3> На базе 5 клинических центров проведено открытое сравнительное многоцентровое рандомизированное клиническое исследование III фазы по изучению эффективности и безопасности Тафалгина у онкологических пациентов с ХБС. Пациенты рандомизированы в две группы: 1-я группа (<i>n</i>=120) получала только Тафалгин подкожно; 2-я группа (<i>n</i>=59) — таблетки морфина 28 дней (период 1) и далее Тафалгин 28 дней (период 2). Первичной конечной точкой эффективности была частота сохранения ответа на обезболивающую терапию к 28-му дню. ХБС оценивали по цифровой рейтинговой шкале (NRS 0/10 баллов); по 5-балльной шкале Лайкерта для пациентов и врачей; по опроснику качества жизни SF-36. Анализ безопасности проводили на основании оценки частоты и выраженности нежелательных явлений (НЯ). <h3>РЕЗУЛЬТАТЫ</h3> Всего обследовано 179 пациентов (популяция ITT); завершили обследование 143 пациента (популяция PP). В 1-й группе доля пациентов с сохранением ответа на обезболивающую терапию к 28-му дню составила 98,97%, во 2-й группе — 100,00% (<i>p</i>=0,6783) для популяции РР. Для популяции ITT: в 1-й группе доля пациентов с сохранением ответа на обезболивающую терапию к 28-му дню была 84,17%, во 2-й группе — 88,14% (<i>p</i>=0,4787). Не выявлено случаев неэффективной терапии Тафалгином. Среднее значение NRS в популяция PP в начале терапии составило 0,42±0,48 и 0,30±0,47 балла в 1-й и 2-й группах (<i>p</i>=0,1250); к 28-му дню — 0,38±0,44 и 0,28±0,30 балла в этих группах (<i>p</i>=0,3472). В популяции ITT: NRS исходно составил 0,53±0,61 и 0,51±0,81 балла в 1-й и 2-й группах, (<i>p</i>=0,3519); к 28-му дню — 0,54±0,81 и 0,41±0,50 балла соответственно, (<i>p</i>=0,4536). После перевода пациентов с морфина на Тафалгин сохранился адекватный контроль боли через 56 и 84 дня терапии. На фоне приема Тафалгина определялась меньшая частота возникновения НЯ. <h3>ЗАКЛЮЧЕНИЕ</h3> Тафалгин оказывает выраженное обезболивающее действие, не уступающее морфину при лечении онкологического ХБС, имеет благоприятный профиль безопасности и меньшую частоту НЯ относительно морфина.

Effect of fertility health awareness strategies on fertility knowledge and childbearing in young married couples (FertStart): study protocol for an effectiveness-implementation hybrid type I multicentre three-arm parallel group open-label randomised clinical trial

IntroductionBirth rates have been declining in many advanced societies including Singapore. We designed two interventions with vastly different resource requirements, which include fertility education, personalised fertility information and a behavioural...

Serum amyloid P component level is associated with clinical response to escitalopram treatment in patients with major depressive disorder

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits, which has been implicated in Alzheimer's disease and major depressive disorder (MDD). However, the relationship between SAP level and depression severity remains obscure. The aims of this study were to investigate how SAP is involved in depression and to explore the association between SAP level and antidepressant treatment response. Patients with MDD (n = 85) who received escitalopram monotherapy for 8–12 weeks were selected from a multicenter open-label randomized clinical trial. The same number of healthy controls was recruited. Depression severity was measured according to the Hamilton Depression Rating Scale (HAMD-17) at baseline and weeks 4, 8, and 12. The plasma levels of SAP were measured at baseline, week 2 and week 12. As a result, baseline levels of SAP were significantly higher in depressed patients than in control subjects (p < 0.001). SAP levels at baseline were negatively associated with depression severity after escitalopram treatment (p < 0.05), and the changes in SAP levels from baseline to week 12 were highly correlated with the severity of depressive symptoms based on the HAMD-17 score (p < 0.05). Interestingly, treatment with escitalopram significantly decreased the plasma levels of SAP in females, but not in males. Altogether, our results suggest that SAP not only involved in the pathobiology of depression but also mediates the action of antidepressant medications.

Randomized clinical study to evaluate the effect of personalized therapy on patients with immunoglobulin A nephropathy.

ABSTRACTBackgroundRandomized controlled trials (RCTs) have been conducted, stratifying idiopathic immunoglobulin A nephropathy (IgAN) patients based on the laboratory findings [serum creatinine, estimated glomerular filtration rate (eGFR) and daily proteinuria]. In contrast, data from kidney biopsy have been used only for clinical diagnosis. Therefore, IgAN patients with active or chronic renal lesions have been receiving the same therapy in experimental and control arms of randomized clinical trials (RCTs).MethodsOur clinical study of IgAN (CLIgAN) is a multicentre, prospective, controlled and open-label RCT based on patients’ stratification at the time of their kidney biopsy. We will consider, first, the type of renal lesions, followed by serum creatinine values, eGFR and proteinuria. Primary and secondary endpoints will be monitored. Then, we will determine whether personalized therapy can slow the decline of renal function and delay end-stage kidney disease.ResultsWe will enrol 132 IgAN patients with active renal lesions (66 patients per arm) in the first RCT (ACIgAN). They will receive corticosteroids combined with renin–angiotensin system blockers (RASBs) or only RASBs. A total of 294 IgAN patients with chronic or moderate renal lesions at high or very high risk of chronic kidney disease (147 patients per arm) will be enrolled in the second RCT (CHRONIgAN), in which they will receive dapagliflozin, a sodium–glucose cotransporter 2 inhibitor, combined with RASBs, or RASBs alone.ConclusionUsing this approach, we hypothesize that patients could receive personalized therapy based on renal lesions to ensure that the right drug gets to the right patient at the right time.

Outcome of low-dose prednisolone use for the induction of remission in lupus nephritis patients.

This study aimed to compare the efficacy of low-dose prednisolone with conventional high-dose regimen in proliferative lupus nephritis (LN) for remission. This open-label randomized clinical trial was conducted in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. A total of 32 LN patients were randomized into low-dose (experimental) and high-dose (control) groups. All subjects received standard dose of intravenous (I/V) methylprednisolone and pulse I/V cyclophosphamide. Oral prednisolone, 0.5mg/kg/d and 1mg/kg/d were given to experimental and control groups respectively for initially 4weeks then tapered. The patients were followed for 24weeks. The rates of renal remission (complete and partial) were assessed at 24weeks. The disease activity, biochemical markers, and quality of life were evaluated at baseline and at 24weeks. Complete renal remission was achieved by 66.7% of patients in each group (P=.99). Renal remission (partial/complete) was achieved by 86.7% and 83.3% of patients in the prednisolone low-dose group and high-dose group respectively (P=.99). In between groups, no significant difference was observed in the improvement of active urinary sediments, serum creatinine level, anti-double-stranded DNA level, complements level, disease activity and Short Form-12 score. The prednisolone dose-related adverse events like cushingoid facies, abdominal stria, infections and serious adverse events like death occurred more in the high-dose prednisolone group. It has been observed that low-dose prednisolone regimen may be effective in LN. Steroid dose-related side effects and rate of infections were lower in this group.

Heart Watch Study: protocol for a pragmatic randomised controlled trial

IntroductionPersonal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed...

Oral Isotretinoin Combined with Oral Terbinafine Versus Oral Terbinafine Alone to Treat Recurrent Dermatophytosis: An Open-Label Randomised Clinical Trial.

Background:Recurrent dermatophytosis is becoming arduous to treat. Recently, oral itraconazole with oral isotretinoin was successful in a patient suffering from recurrent dermatophytosis.Objectives:To evaluate if oral isotretinoin confers any added benefit over oral terbinafine in the treatment of recurrent dermatophytosis.Materials and Methods:This was an open-label randomized clinical trial including 100 adult patients with recurrent tinea cruris and/or tinea corporis randomized into two groups; Group A (oral isotretinoin 0.5 mg/kg/day and oral terbinafine 250 mg twice daily) and Group B (oral terbinafine 250 mg twice daily) for 4 weeks, and followed up for 3 months. Fungal culture and antifungal susceptibility testing against terbinafine, fluconazole, amphotericin B, itraconazole, and griseofulvin were performed.Results:Out of the 100 patients, 91 patients (44 in Group A and 47 in Group B) completed the trial. Complete cure was seen in 19/44 (43.18%) patients in Group A and 20/47 (42.55%) patients in Group B (P = 0.951). Recurrence occurred in 12/19 (63.1%) patients in Group A and 13/20 (65%) patients in Group B (P = 0.904). Cheilitis and dryness of lips were the most common adverse effects seen in 32/44 (72.73%) patients in Group A. A total of 50 cultures were grown. The commonest species isolated was Trichophyton interdigitale in 36 (72%) patients, having a mean minimum inhibitory concentration of 3.13 μg/mL for terbinafine. However, for itraconazole, it was 0.13 μg/mL, and varied minimum inhibitory concentration (MIC) values were seen for fluconazole, griseofulvin, and amphotericin B.Conclusion:The addition of isotretinoin to terbinafine has no added benefit in treating patients with recurrent dermatophytosis.

Role of stent oversizing in patients undergoing primary percutaneous coronary intervention. An open-labeled randomized controlled trial.

In patients with ST-segment-elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PPCI) is the treatment of choice. Stent undersizing might occur due to catecholamine release and coronary spasm. Although routine oversizing has been promising in several investigations, it has never been tested in randomized clinical trials. In this single-center open-label randomized clinical trial, we evaluated the role of stent oversizing in PPCI. Candidates for PPCI were randomly divided into oversized and non-oversized groups. In the oversized group, the stent was oversized by 10% according to the mean lumen diameter, retrieved from the quantitative coronary analysis. Primary composite endpoints were defined as the occurrence of complete total ST-segment (STR)resolution and postprocedural thrombolysis in myocardial infarction (TIMI) flow grade III. The study population was comprised of 122 patients, allocated to the oversized group (N.=61) and the non-oversized group (N.=61). There was no significant difference between the 2 groups regarding the final TIMI flow grade. Complete STR was marginally more favorable in the non-oversized group (56.05±55.12 vs. 64.64±23.28; P=0.056). The troponin ratio, CK-MB ratio, and 6-month follow-up outcome - defined as target lesion revascularization, heart failure, and cardiovascular death - were comparable between the 2 groups. Our study showed that routine oversizing in patients undergoing PPCI had no benefit regarding ST-segment resolution and the final TIMI flow, as well as hard cardiac events, during the follow-up.

Investigation of Effectiveness of Two Different Kinesiotaping Techniques in Myofascial Pain Syndrome: An Open-Label Randomized Clinical Trial

Myofascial pain syndrome is a regional musculoskeletal pain syndrome characterized by trigger points. Although there are widely accepted treatment modalities, there is no gold standard treatment. Kinesiotaping represents an interesting modality in the treatment of musculoskeletal disorders and attracts attention with studies emerging in the recent years, but in spite of the proposed benefits of kinesiotaping, its efficacy is still unclear, thus further studies evaluating the effectiveness of kinesiotaping are needed. We aimed to investigate, not only the effectiveness of kinesiotaping applied with the space correction and muscle inhibition techniques (compared to the home exercise program in reducing pain and improving functional status and quality of life in female patients with myofascial pain syndrome related to active trigger points in the upper trapezius), but also to evaluate the superiority of the 2 techniques over each other. An open-label randomized clinical trial with a parallel assignment intervention model. The physical medicine and rehabilitation clinics in Istanbul University, Istanbul Faculty of Medicine. Seventy-one female patients with the complaint of pain in the upper trapezius region, diagnosed with myofascial pain syndrome, and having at least one active trigger point in the upper trapezius fibers, were randomly assigned by a computer program to 1 of the 3 groups: kinesiotaping with the space correction technique (KSCT, n = 20), kinesiotaping with the muscle inhibition technique (KMIT, n = 24), and the home exercise program alone (control group [CG], n = 27). The patients were evaluated by the numerical rating scale for pain intensity, the neck disability index for functional status, and the 36-Item Short-Form Health Survey for quality of life in the beginning of the study and at the first, second, and sixth weeks (1-month follow-up). Kinesiotaping was associated with lower pain intensity levels (P = 0.019 at the first week and P = 0.026 at the second week) and better functional status (P = 0.011 at the second week) and it was effective in increasing quality of life by improving physical functions and general health (P = 0.033 and P = 0.003 at the second week, respectively) earlier than in the CG. Role limitations due to physical factors improved in the KMIT group earlier than in the other groups (P = 0.022 at the second week). Being performed in a limited number of female patients only, absence of a placebo group, and lack of blinded assessments. Both kinesiotaping methods were associated with lower pain intensity levels and better functional status and were effective in increasing quality of life by improving physical functions and general health earlier than the home exercise program. There was no significant difference between the kinesiotaping methods, except for role limitations due to the physical factors domain of SF-36 which was improved in the KMIT group earlier than in the KSCT group and CGs.

MP36-03 IMPACT OF TESTOSTERONE THERAPY ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF TWO OPEN-LABEL RANDOMIZED CLINICAL TRIALS OF TESTOSTERONE PELLETS, INJECTIONS, AND INTRANASAL GEL IN HYPOGONADAL MEN

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-03 IMPACT OF TESTOSTERONE THERAPY ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF TWO OPEN-LABEL RANDOMIZED CLINICAL TRIALS OF TESTOSTERONE PELLETS, INJECTIONS, AND INTRANASAL GEL IN HYPOGONADAL MEN Daniel Gonzalez, Eliyahu Kresch, Jesse Ory, Sirpi Nackeeran, Ruben Blachman-Braun, Manuel Molina, and Ranjith Ramasamy Daniel GonzalezDaniel Gonzalez More articles by this author , Eliyahu KreschEliyahu Kresch More articles by this author , Jesse OryJesse Ory More articles by this author , Sirpi NackeeranSirpi Nackeeran More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Manuel MolinaManuel Molina More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone replacement therapy (TRT) can potentially cause infertility via suppression of HPG axis. Intratesticular testosterone (ITT) is vital for spermatogenesis and can be reliably evaluated with serum 17-hydroxyprogesterone (17-OHP) as a serum biomarker. We hypothesized that long-acting TRT will have a significant impact on suppressing ITT production as compared to short-acting TRT. We evaluated data from two simultaneous open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous T pellets and (Trial II) Intranasal Testosterone or Intramuscular Testosterone cypionate (TC). METHODS: Hypogonadal men (2 serum T <300 ng/dL by LC-MS/MS) were randomized into open-label randomized clinical trials. Eligible subjects received: 800mg subcutaneous T pellets or 11mg TID Intranasal T or 200mg x 2 weeks TC for 2 months. Serum T and 17-OHP were collected at baseline and follow-up. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as the mean percent change (SD). Paired sample analysis (baseline versus follow-up) was performed with Student's T-test to determine change within the different preparations. RESULTS: ITT via 17-OHP significantly decrease among men receiving all the different T preparations.(Fig. 1) Of note, longer acting TRT such as pellets and TC demonstrated the greatest % decrease in 17-OHP, -64 +29 ng/dL and -54 + 31 ng/dL, respectively (p<0.05) as compared to nasal T gel. Shorter acting T preparations such as nasal T gel demonstrated a mean % decrease in 17-OHP -38 +26 (p=0.008), but to a lesser extent as pellets. Changes in ITT paralleled with subjective changes in testis size, with men receiving nasal T gel reported maintenance of testis size whereas those with T pellets or TC reported decreased testis size. CONCLUSIONS: Intranasal T and other short acting forms of TRT may help hypogonadal men maintain ITT and testis size that is critical for maintaining spermatogenesis and fertility potential. The differential effects of TRT (based on half-life) on intratesticular T is novel and should be considered during the decision making for hypogonadal men who wish to preserve future fertility. Source of Funding: Investigator Initiated Grants from Acerus Pharmaceuticals, Canada and Empower Pharmacy © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e636-e637 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Gonzalez More articles by this author Eliyahu Kresch More articles by this author Jesse Ory More articles by this author Sirpi Nackeeran More articles by this author Ruben Blachman-Braun More articles by this author Manuel Molina More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement Loading ...

No effect of approved fibromyalgia drugs on the social pain (invalidation) contrary to physical pain: an open-label short-term randomized clinical trial.

The social pain or invalidation denoting painful feeling following social conflicts or misunderstanding about illness legitimacy has been proposed as a salient disabling symptom besides physical pain or non-pain symptoms in fibromyalgia (FM). We sought to evaluate the effect of 1-month administration of duloxetine or pregabalin on the invalidation dimensions in FM patients with respect to the comparison of these two drugs on this issue. This open-label randomized clinical trial study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Primary outcome measure (Illness Invalidation Inventory (3*I)) and secondary outcome measures (Beck Depression Inventory-II (BDI-II), widespread pain index (WPI), and polysymptomatic distress scale (PSD)) were compared before and after treatment, using paired t test or Wilcoxon signed test. Of 81 eligible FM patients, 44 patients in the duloxetine arm and 27 patients in the pregabalin arm completed the study protocol. Overall, no significant improvement was seen in 3*I scores after treatment with either duloxetine or pregabalin, except in the lack of understanding of medical professionals which improved after treatment with pregabalin (2.43 ± 1.38 to 1.79 ± 0.94, p value: 0.01). There were no intragroup and intergroup differences in the effects of duloxetine and pregabalin on 3*I scores when adjusted with the cofounders. Both duloxetine and pregabalin improved WPI, BDI-II, and PSD scores significantly. Short-term FM pharmacological treatment had no effect on social pain. This finding was regardless of drug type, improvement of physical pain, and depression.

Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic

Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms. To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19. This prospective open-label single-site randomized clinical trial used a 1:1 block randomization design to examine emotional exhaustion and burnout symptoms among frontline health care professionals (physicians, nurses, and physical therapists) working with patients with COVID-19 at the Ribeirão Preto Medical School University Hospital in São Paulo, Brazil. Participants were enrolled between June 12 and November 12, 2020. A total of 214 health care professionals were recruited and assessed for eligibility, and 120 participants were randomized in a 1:1 ratio by a researcher who was not directly involved with data collection. Cannabidiol, 300 mg (150 mg twice per day), plus standard care or standard care alone for 28 days. The primary outcome was emotional exhaustion and burnout symptoms, which were assessed for 28 days using the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel. A total of 120 participants were randomized to receive either CBD, 300 mg, plus standard care (treatment arm; n = 61) or standard care alone (control arm; n = 59) for 28 days. Of those, 118 participants (59 participants in each arm; 79 women [66.9%]; mean age, 33.6 years [95% CI, 32.3-34.9 years]) received the intervention and were included in the efficacy analysis. In the treatment arm, scores on the emotional exhaustion subscale of the Maslach Burnout Inventory significantly decreased at day 14 (mean difference, 4.14 points; 95% CI, 1.47-6.80 points; partial eta squared [ηp2] = 0.08), day 21 (mean difference, 4.34 points; 95% CI, 0.94-7.73 points; ηp2 = 0.05), and day 28 (mean difference, 4.01 points; 95% CI, 0.43-7.59 points; ηp2 = 0.04). However, 5 participants, all of whom were in the treatment group, experienced serious adverse events: 4 cases of elevated liver enzymes (1 critical and 3 mild, with the mild elevations reported at the final 28-day assessment) and 1 case of severe pharmacodermia. In 2 of those cases (1 with critical elevation of liver enzymes and 1 with severe pharmacodermia), CBD therapy was discontinued, and the participants had a full recovery. In this study, CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic. However, it is necessary to balance the benefits of CBD therapy with potential undesired or adverse effects. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings. ClinicalTrials.gov Identifier: NCT04504877.

Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer

Nivolumab plus ipilimumab is superior to platinum-based chemotherapy in treatment-naive advanced non-small cell lung cancer (NSCLC). Nivolumab is superior to docetaxel in advanced pretreated NSCLC. To determine whether the addition of ipilimumab to nivolumab improves survival in patients with advanced, pretreated, immunotherapy-naive squamous (Sq) NSCLC. The Lung Cancer Master Protocol (Lung-MAP) S1400I phase 3, open-label randomized clinical trial was conducted from December 18, 2015, to April 23, 2018, randomizing patients in a 1:1 ratio to nivolumab alone or combined with ipilimumab. The median follow-up in surviving patients was 29.5 months. The trial was conducted through the National Clinical Trials Network and included patients with advanced immunotherapy-naive SqNSCLC and a Zubrod score of 0 (asymptomatic) to 1 (symptomatic but completely ambulatory) with disease progression after standard platinum-based chemotherapy. Randomization was stratified by sex and number of prior therapies (1 vs 2 or more). Data were analyzed from May 3, 2018, to February 1, 2021. Nivolumab, 3 mg/kg intravenously every 2 weeks, with or without ipilimumab, 1 mg/kg intravenously every 6 weeks, until disease progression or intolerable toxic effects. The primary end point was overall survival (OS). Secondary end points included investigator-assessed progression-free survival (IA-PFS) and response per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. Of 275 enrolled patients, 252 (mean age, 67.5 years [range 41.8-90.3 years]; 169 men [67%]; 206 White patients [82%]) were deemed eligible (125 randomized to nivolumab/ipilimumab and 127 to nivolumab). The study was closed for futility at a planned interim analysis. Overall survival was not significantly different between the groups (hazard ratio [HR], 0.87; 95% CI, 0.66-1.16; P = .34). Median survival was 10 months (95% CI, 8.0-14.4 months) in the nivolumab/ipilimumab group and 11 months (95% CI, 8.6-13.7 months) in the nivolumab group. The IA-PFS HR was 0.80 (95% CI, 0.61-1.03; P = .09); median IA-PFS was 3.8 months (95% CI, 2.7-4.4 months) in the nivolumab/ipilimumab group and 2.9 months (95% CI, 1.8-4.0 months) in the nivolumab alone group. Response rates were 18% (95% CI, 12%-25%) with nivolumab/ipilimumab and 17% (95% CI, 10%-23%) with nivolumab. Median response duration was 28.4 months (95% CI, 4.9 months to not reached) with nivolumab/ipilimumab and 9.7 months with nivolumab (95% CI, 4.2-23.1 months). Grade 3 or higher treatment-related adverse events occurred in 49 of 124 patients (39.5%) who received nivolumab/ipilimumab and in 41 of 123 (33.3%) who received nivolumab alone. Toxic effects led to discontinuation in 31 of 124 patients (25%) on nivolumab/ipilimumab and in 19 of 123 (15%) on nivolumab. In this phase 3 randomized clinical trial, ipilimumab added to nivolumab did not improve outcomes in patients with advanced, pretreated, immune checkpoint inhibitor-naive SqNSCLC. ClinicalTrials.gov Identifier: NCT02785952.

Effect of Cytisine vs Varenicline on Smoking Cessation

Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy. To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation. This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome. Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support. The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025. Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002). Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation. anzctr.org.au Identifier: ACTRN12616001654448.

Home Health Management of Parkinson Disease Deep Brain Stimulation

The travel required to receive deep brain stimulation (DBS) programming causes substantial burden on patients and limits who can access DBS therapy. To evaluate the efficacy of home health DBS postoperative management in an effort to reduce travel burden and improve access. This open-label randomized clinical trial was conducted at University of Florida Health from November 2017 to April 2020. Eligible participants had a diagnosis of Parkinson disease (PD) and were scheduled to receive DBS independently of the study. Consenting participants were randomized 1:1 to receive either standard of care or home health postoperative DBS management for 6 months after surgery. Primary caregivers, usually spouses, were also enrolled to assess caregiver strain. The home health postoperative management was conducted by a home health nurse who chose DBS settings with the aid of the iPad-based Mobile Application for PD DBS system. Prior to the study, the home health nurse had no experience providing DBS care. The primary outcome was the number of times each patient traveled to the movement disorders clinic during the study period. Secondary outcomes included changes from baseline on the Unified Parkinson's Disease Rating Scale part III. Approximately 75 patients per year were scheduled for DBS. Of the patients who met inclusion criteria over the entire study duration, 45 either declined or were excluded for various reasons. Of the 44 patients enrolled, 19 of 21 randomized patients receiving the standard of care (mean [SD] age, 64.1 [10.0] years; 11 men) and 23 of 23 randomized patients receiving home health who underwent a minimum of 1 postoperative management visit (mean [SD] age, 65.0 [10.9] years; 13 men) were included in analysis. The primary outcome revealed that patients randomized to home health had significantly fewer clinic visits than the patients in the standard of care arm (mean [SD], 0.4 [0.8] visits vs 4.8 [0.4] visits; P < .001). We found no significant differences between the groups in the secondary outcomes measuring the efficacy of DBS. No adverse events occurred in association with the study procedure or devices. This study provides evidence supporting the safety and feasibility of postoperative home health DBS management. ClinicalTrials.gov Identifier: NCT02474459.

Comparison of azithromycin versus erythromycin on gestation length (prolongation of latency interval) and neonatal outcomes in pregnant women with premature rupture of the membrane: an open-label randomized clinical trial

Background: Premature rupture of membrane (PROM) is an important problem among pregnant women, which leads to maternal and neonatal morbidity.This study was done to compare the efficacy of azithromycin with erythromycin on the pregnancy length and the neonatal adverse effects in mothers with PROM.Materials and Methods: In this open-label randomized clinical trial, 194 pregnant women with PROM who referred to Akbarabadi Hospital were enrolled and randomly assigned to two groups. Group I received oral Azithromycin (1 gr/orally), Abidi Company Iran ) + Ampicillin 2 gram IV )Abidi Company, Iran) every six hours for 48 hours; then, only Amoxicillin 500 mg every eight hours for five days. and group II recived intravenous Erythromycin (Abidi Company, Iran) 400 mg every six hours for seven days + Ampicillin 2 grams IV every six hours for 48 hours, then Amoxicillin 500 mg every six hours for five days Finally the pregnancy length and neonatal adverse effects or neonatal outcomes compared between two groups.Result: There was no significant difference between the groups in mean of pregnancy length (32.5 versus 32.6 weeks, respectively, p=0.757) Also the frequency ofIntraventricular hemorrhage, Necrotizing enterocolitis, Respiratory Distress Syndrome sepsis, icter, oxygen demand, ICU admission, duration of hospitalization in the NICU, and mortality in neonate were same between the groups. The mean of patient satisfaction (by self-report) was 9.8 and 9.5 in group I, II, respectivel (P=0.001).Conclusion: It can be concluded that oral azithromycin and intravenous erythromycin have the same effect on increasing the duration of pregnancy and reducing neonatal complications in women with PROM. But azithromycin was associated with greater satisfaction and its use is recommended.