Short-acting Formulations Research Articles

Evaluating preferences for medication formulation and treatment model among people who use opioids non-medically: A web-based cross-sectional study

IntroductionOver the past decade, treatment for opioid use disorder has expanded to include long-acting injectable and implantable formulations of medication for opioid use disorder (MOUD), and integrated treatment models systematically addressing both behavioral and physical health. Patient preference for these treatment options has been underexplored. Gathering data on OUD treatment preferences is critical to guide the development of patient-centered treatment for OUD. This cross-sectional study assessed preferences for long-acting MOUD and integrated treatment using an online survey. MethodsAn online Qualtrics survey assessed preferences for MOUD formulation and integrated treatment models. The study recruited participants (n = 851) in October and November 2019 through advertisements or posts on Facebook, Google AdWords, Reddit, and Amazon Mechanical Turk (mTurk). Eligible participants scored a two or higher on the opioid pain reliever or heroin scales of the Tobacco, Alcohol Prescription Medication and other Substance Use (TAPS) Tool. Structured survey items obtained patient preference for MOUD formulation and treatment model. Using stated preference methods, the study assessed preference via comparison of preferred options for MOUD and treatment model. ResultsIn the past year, 824 (96.8 %) participants reported non-prescribed use of opioid pain relievers (mean TAPS score = 2.72, SD = 0.46) and 552 (64.9 %) reported heroin or fentanyl use (mean TAPS score = 2.73, SD = 0.51). Seventy-four percent of participants (n = 631) reported currently or previously receiving OUD treatment, with 407 (48.4 %) receiving MOUD. When asked about preferences for type of MOUD formulation, 452 (53.1 %) preferred a daily oral formulation, 115 (13.5 %) preferred an implant, 114 (13.4 %) preferred a monthly injection and 95 (11.2 %) preferred a weekly injection. Approximately 8.8 % (n = 75) would not consider MOUD regardless of formulation. The majority of participants (65.2 %, n = 555) preferred receiving treatment in a specialized substance use treatment program distinct from their medical care, compared with receiving care in an integrated model (n = 296, 34.8 %). ConclusionsThough most participants expressed willingness to try long-acting MOUD formulations, the majority preferred short-acting formulations. Likewise, the majority preferred non-integrated treatment in specialty substance use settings. Reasons for these preferences provide insight on developing effective educational tools for patients and suggesting targets for intervention to develop a more acceptable treatment system.

Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. A total of 40276 tramadol, 141023 hydrocodone, and 45221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.

The effect of parenteral vitamin B12 on the growth rate of dairy calves over the summer and autumn on seven farms from the Central Plateau, New Zealand

ABSTRACTAimsTo investigate the effect of parenteral vitamin B12 supplementation on the growth rate of dairy heifer calves over the summer and autumn on seven farms from the Central Plateau of New Zealand, an area historically associated with low cobalt levels in grazing pasture.MethodsThis was a controlled clinical trial conducted on a convenience sample of seven farms with young female calves randomly assigned to three vitamin B12 treatment groups and followed through a grazing season. Two treatment groups received either monthly SC injections of a short-acting (SA) B12 formulation or 3-monthly injections of a long-acting (LA) B12 formulation and the third group received no treatment (NT). No additional parenteral vitamin B12 was given; however, all calves received additional cobalt (0.04–0.4 mg Co/kg liveweight) in the mineralised anthelmintic drenches given orally every month. Liveweight was recorded in December/January and at the end of the trial in May/June/July depending on farm. Pasture cobalt concentrations (mg/kg DM) were measured every month using 500-g herbage samples from 100-m transects in the area about to be grazed by the trial groups.ResultsThere was evidence for a difference in growth rate between groups with mean final weight of 228 (95% CI = 212–243) kg for the LA groups, 224 (95% CI = 209–239) kg for the SA groups and 226 (95% CI = 211–241) kg for the NT groups respectively, (global p-value = 0.014). Calves given SA vitamin B12 were 3.77 (95% CI = 0.71–6.82) kg lighter than calves given LA vitamin B12 (p = 0.011). There was no evidence for a change in pasture cobalt concentrations (p = 0.32).Conclusions and clinical relevanceThe results of this trial raise the question as to whether the routine use of vitamin B12 supplementation in young cattle from areas traditionally thought to be cobalt deficient is necessary, and further raise the possibility that vitamin B12 supplementation by repeated injection of SA products may negatively impact growth rates.

Predictors of persistent postoperative opioid use following colectomy: a population-based cohort study from England.

This retrospective cohort study on adults undergoing colectomy from 2010 to 2019 used linked primary (Clinical Practice Research Datalink), and secondary (Hospital Episode Statistics) care data to determine the prevalence of persistent postoperative opioid use following colectomy, stratified by pre-admission opioid exposure, and identify associated predictors. Based on pre-admission opioid exposure, patients were categorised as opioid-naïve, currently exposed (opioid prescription 0-6 months before admission) and previously exposed (opioid prescription within 7-12 months before admission). Persistent postoperative opioid use was defined as requiring an opioid prescription within 90 days of discharge, along with one or more opioid prescriptions 91-180 days after hospital discharge. Multivariable logistic regression analyses were conducted to obtain odds ratios for predictors of persistent postoperative opioid use. Among the 93,262 patients, 15,081 (16.2%) were issued at least one opioid prescription within 90 days of discharge. Of these, 6791 (45.0%) were opioid-naïve, 7528 (49.9%) were currently exposed and 762 (5.0%) were previously exposed. From the whole cohort, 7540 (8.1%) developed persistent postoperative opioid use. Patients with pre-operative opioid exposure had the highest persistent use: 5317 (40.4%) from the currently exposed group; 305 (9.8%) from the previously exposed group; and 1918 (2.5%) from the opioid-naïve group. The odds of developing persistent opioid use were higher among individuals who used long-acting opioid formulations in the 180 days before colectomy than those who used short-acting formulations (odds ratio 3.41 (95%CI 3.07-3.77)). Predictors of persistent opioid use included: previous opioid exposure; high deprivation index; multiple comorbidities; use of long-acting opioids; white race; and open surgery. Minimally invasive surgical approaches were associated with lower odds of persistent opioid use and may represent a modifiable risk factor.

Inpatient prescribing patterns of long-acting injectables and their oral or short-acting injectable equivalent formulations.

Background: Long-acting injectable (LAI) antipsychotics (APs) each have an oral equivalent formulation, while aripiprazole, olanzapine, and ziprasidone each also have a short-acting injectable (SAI) equivalent formulation. Inpatient prescribing patterns of LAIs and their oral/SAI equivalents are less characterized in populations other than Medicaid, Medicare, and Veterans Affairs populations. Mapping out inpatient prescribing patterns remains an important first step to ensure appropriate use of antipsychotics during this critical juncture of patient care prior to discharge. This study determined inpatient prescribing patterns of first- (FGA) and second-generation antipsychotic (SGA) LAIs and their oral/SAI formulations. Methods: This was a large retrospective study using the Cerner Health Facts® database. Hospital admissions due to schizophrenia, schizoaffective disorder, or bipolar disorder from 2010 to 2016 were identified. AP utilization was defined as the proportion of inpatient stays during which at least 1 AP was administered to the total number of inpatient visits over the observed period. Descriptive analyses were used to determine prescribing patterns for APs. Chi-square tests were used to determine utilization differences across years. Results: 94,989 encounters were identified. Encounters during which oral/SAI of SGA LAIs were administered were most common (n = 38,621, 41%). Encounters during which FGA LAIs or SGA LAIs were administered were the least common (n = 1,047, 1.1%). Prescribing patterns differed across years (p < 0.05) within the SGA LAI subgroup analysis (N = 6,014). Paliperidone palmitate (63%, N = 3,799) and risperidone (31%, N = 1,859) were the most frequently administered. Paliperidone palmitate utilization increased from 30% to 72% (p < 0.001), while risperidone utilization decreased from 70% to 18% (p < 0.001). Conclusions: Compared with their oral or SAI formulations, LAIs were underutilized from 2010 to 2016. Among SGA LAIs, the prescribing patterns of paliperidone palmitate and risperidone changed significantly.

Sustained-Release Powders Based on Polymer Particles for Pulmonary Delivery of Beclomethasone Dipropionate in the Treatment of Lung Inflammation.

Inhaled corticosteroids are the mainstay in the management of lung inflammation associated to chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Nonetheless, available inhalation products are mostly short-acting formulations that require frequent administrations and do not always produce the desired anti-inflammatory effects. In this work, the production of inhalable beclomethasone dipropionate (BDP) dry powders based on polymeric particles was attempted. As starting material, the PHEA-g-RhB-g-PLA-g-PEG copolymer was chosen, obtained by grafting 0.6, 2.4 and 3.0 mol%, respectively, of rhodamine (RhB), polylactic acid (PLA) and polyethylene glycol 5000 (PEG) on alpha,beta-poly(N-2-hydroxyethyl)DL-aspartamide (PHEA). The drug was loaded into the polymeric particles (MP) as an inclusion complex (CI) with hydroxypropyl-cyclodextrin (HP-β-Cyd) (at a stoichiometric ratio of 1:1) or as free form. The spray-drying (SD) process to produce MPs was optimized by keeping the polymer concentration (0.6 wt/vol%) constant in the liquid feed and by varying other parameters such as the drug concentration. The theoretical aerodynamic diameter (daer) values among the MPs are comparable and potentially suitable for inhalation, as confirmed also through evaluation of the experimental mass median aerodynamic diameter (MMADexp). BDP shows a controlled release profile from MPs that is significantly higher (more than tripled) than from Clenil®. In vitro tests on bronchial epithelial cells (16HBE) and adenocarcinomic human alveolar basal epithelial cells (A549) showed that all the MP samples (empty or drug-loaded) were highly biocompatible. None of the systems used induced apoptosis or necrosis. Moreover, the BDP loaded into the particles (BDP-Micro and CI-Micro) was more efficient than free BDP to counteract the effects of cigarette smoke and LPS on release of IL-6 and IL-8.

MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL Marco-Jose Rivero, Jesse Ory, Halifax Canada, Parris Diaz, Raul Clavijo, Nannan Thirumavalavan, Ruben Blachman-Braun, Justin Loloi, Ari Bernstein, and Ranjith Ramasamy Marco-Jose RiveroMarco-Jose Rivero More articles by this author , Jesse OryJesse Ory More articles by this author , Halifax CanadaHalifax Canada More articles by this author , Parris DiazParris Diaz More articles by this author , Raul ClavijoRaul Clavijo More articles by this author , Nannan ThirumavalavanNannan Thirumavalavan More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Justin LoloiJustin Loloi More articles by this author , Ari BernsteinAri Bernstein More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone therapy is associated with rise in hematocrit (HCT) and subsequent risk of polycythemia and thrombotic events. Incidence of these side effects may vary depending on the route of administration of testosterone therapy formulation. In this study, we compared the effects of intranasal testosterone gel (NT) and intramuscular testosterone cypionate (TC) on HCT and serum total testosterone (T) levels in testosterone-deficient men over 4 months. METHODS: Patients between 18 and 75 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency (TD) was defined as two measurements of serum total testosterone below 300 ng/dL combined with one or more characteristic clinical symptoms. Men were randomized (1:1) to receive either NT (5.5 mg per nostril) three times a day or TC (200 mg intramuscularly) once every two weeks. The primary outcomes were changes in HCT and serum T before and after 4 months of treatment. Secondary outcomes were changes in estradiol, prostate-specific antigen, and 17-hydroxyprogesterone. RESULTS: 49 men were randomized to receive either NT (n=20) or TC (n=29). The median participant age was 47 years with a mean serum T of 236.6 ng/dL and mean HCT of 43.3%. The prevalence of participants who screened positive for obstructive sleep apnea on STOP-BANG questionnaire was 70% for the NT group and 72% for the TC group. Men in both groups experienced significantly increased serum T levels throughout the study period (p<0.001), although a larger increase was seen in the TC group. There was an increase in the mean HCT of the TC group from 42.6% to 46.0% at 4-month follow-up (p=0.006), while the NT group experienced no significant changes in mean HCT (p=0.903). The TC group experienced significant increases in estradiol (p<0.001) and decreases in 17-hydroxyprogesterone (p<0.001) at 4-month follow-up, while the NT group experienced no such changes. CONCLUSIONS: Although both NT and TC regimens are effective in treating men with TD, NT does not appear to significantly affect HCT levels. Patients who are at increased risk of developing polycythemia or those who wish to avoid changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as NT. Source of Funding: This project was funded by an investigator-initiated grant provided by Acerus Pharmaceuticals © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1142 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco-Jose Rivero More articles by this author Jesse Ory More articles by this author Halifax Canada More articles by this author Parris Diaz More articles by this author Raul Clavijo More articles by this author Nannan Thirumavalavan More articles by this author Ruben Blachman-Braun More articles by this author Justin Loloi More articles by this author Ari Bernstein More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

Testosterone Propionate Promotes Proliferation and Viability of Bone Marrow Mesenchymal Stem Cells while Preserving Their Characteristics and Inducing Their Anti-Cancer Efficacy

Various studies have reported the effects of testosterone on different cell types, yet bone marrow-derived mesenchymal stem cells’ cellular responses to testosterone remain unknown. To investigate the effects of testosterone propionate, an oil-soluble short-acting form of testosterone, on human bone marrow-derived mesenchymal stem cells’ proliferation and viability after 24 hours of incubation. We also investigated the impact of testosterone propionate on bone marrow-derived mesenchymal stem cell’s polarization and cytotoxicity on K562 leukemia cell line. In vitro study. We expanded commercially available bone marrow derived mesenchymal stem cells in vitro and treated them with testosterone propionate at concentrations ranging from 10-6-10-10 M for 24 hours. Ideal concentration was determined by evaluating cellular viability and proliferation with Annexin V/Propidium Iodide assay and carboxyfluorescein succinimidyl ester staining. The characteristic features of bone marrow-derived mesenchymal stem cells were evaluated by immunophenotyping and investigating their differentiation capacities. Bone marrow-derived mesenchymal stem cells’ cytotoxic properties upon testosterone propionate treatment were determined by co-culturing the cells with K562 cells and with confocal imaging investigating polarization. Testosterone propionate promoted proliferation and maintained the viability of bone marrow-derived mesenchymal stem at 10-8 M concentration. Further evaluations were conducted with the determined dose. The results showed that, apart from promoting mesenchymal stem cells’ polarization and increasing their cytotoxicity on K562 cells, testosterone propionate did not alter differentiation capacities of bone marrow-derived mesenchymal stem cells and certain cell surface markers, but led to a significant increase in HLA-DR expression. The findings reveal that testosterone propionate promotes the proliferation and survival of bone marrow-derived mesenchymal stem cells in a dose-dependent manner without hampering their differentiation capacities, induces their polarization to the pro-inflammatory phenotype, and increases their cytotoxicity on the K562 cell line.

Farmakoterapija kancerskog bola opioidnim analgeticima

Introduction: Selection of analgesics should be based on the World Health Organization (WHO) analgesic ladder, beginning with non-opioid analgesics in combination with adjuvants for mild pain, weak opioids with adjuvants are indicated for moderate pain, while potent opioids, non-opioids and adjuvants are recommended for severe pain. Methods: The facts presented in this paper are expanded by searching for recent literature data in the following index-data-bases: SCI index, PubMed, Google Scholar, Scopus, and by using adequate key words. The idea supporting this paper was to make practice easier for clinicians who are engaged in supportive oncology and to help in adequate and up-to-date malignant pain management in oncology patients in everyday practice. Topic: Initial opioid dose should be low, and long-acting opioid dose should be gradually increased and titrated considering daily requirements of short-acting opioid formulation due to pain breakthrough. It is mandatory for patients on long-acting opioid treatment to be provided with fast-acting medication for breakthrough pain treatment. The following long-acting strong opioids formulations are available in Serbia - oxycodone, oxycodone/ naloxone fixed combination, hydromorphone, tapentadol, fentanyl. A patient and his/her family should be warned about possible side effects of opioids, primarily morphine. There is great fear of prescribing opioid analgesics due to their possible side-effect of tory depression. Opiophobia is defined as exaggerated concern about the consequences of medical use of opioids. The risk of opioids is estimated to overweight the benefits of the treatment, resulting in the fact that they are not used where indicated. Avoiding opioid prescriptions is one of the biggest barriers for successful treatment of cancer pain. Conclusion: Oncology patients with moderate and severe pain have a constitutional right not to tolerate pain and they have a right to strong opioid treatment. Implementation of analgesic elevator is recommended. There should not be any fear of addiction or other side-effects that can be controlled, and the benefits greatly outweigh the risks of possible side-effects in these patients. Cancer pain management should be an equally important element of overall cancer treatment. Only by multimodal and multidisciplinary treatment approach satisfactory analgesic effects may be achieved while minimizing adverse side-effects.

Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure

BackgroundIvabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily. ObjectivesThis study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF. MethodsPatients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32. ResultsWe randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm. ConclusionsThe present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082)

Assessment of the Safety and Efficacy of Pre-emptive Use of Extended-release Buprenorphine for Mouse Laparotomy.

Buprenorphine is commonly used to control postoperative pain in rodents. Short-acting formulations of buprenorphine (bup-HCl) require frequent handling and restraint of animals for appropriate dosing, which can be stressful and confound research outcomes. Ethiqa XR (bup-ER) is an FDA-indexed extended-release buprenorphine formulation that is an alternative to bup-HCl in mice and rats. In the current study, we first evaluated the pharmacokinetics of bup-ER in male C57BL/6J mice by sampling blood at 10 time points, ranging from 30 min to 72 h after administration (n = 3 mice per time point). Average plasma concentrations fell below therapeutic levels at 48 h after administration. We also evaluated the safety of bup-ER when administered prior to surgery in combination with common anesthetics and the efficacy of bup-ER in mouse laparotomy. Anesthetic safety was studied by measuring respiratory rate, rectal temperature, and recovery time in groups of mice (n = 8) given bup-HCl, bup-ER, or saline in combination with isoflurane or ketamine-xylazine anesthesia. No differences were seen between analgesic treatment groups with either of the general anesthetics. To evaluate efficacy, mice (n = 10) were randomly allocated to receive either bup-ER (3.25 mg/kg) once presurgically, bup-HCl (0.1 mg/kg) presurgically and then every 8 h, or saline once before surgery. Mice underwent a sham laparotomy and were assessed for pain based on changes in weight, cageside ethogram, nesting consolidation test, rearing frequency, and nociception to von Frey testing at 6, 12, 24, 48, and 72 h after surgery. Cageside ethogram, rearing frequency, and von Frey testing showed significant differences between bup-ER-treated mice and saline controls in the early postoperative period. No significant effects between treatment groups were seen in daily weights or nesting consolidation scores. This study demonstrates that bup-ER can be safely administered before surgery and provides analgesia for up to 48 h after administration based on pharmacokinetic and behavioral data.

Increased AMH plasma concentration and small antral follicles - Deslorelin slow release implants as a promising tool for preparation of mares for OPU?

A major factor affecting oocyte yield during ovum pick-up (OPU) procedures in mares is the number of follicles present on the ovary and the associated number of recovered oocytes (Cuervo-Arango et al. Reproduction, Fertility and Development. 2019; 31(12): 1894-1903). The interest in manipulation of ovarian follicular populations in horses is increasing because of benefits with regard to the oocyte yield and the overall outcome for assisted reproductive procedures. This study aimed to evaluate effects of slow-release implants containing deslorelin acetate on antral follicle counts (AFC), follicular subpopulations of different size ranges and plasma anti-Mullerian hormone (AMH) and gonadotrophin concentration in mares. Haflinger mares (n=12) were synchronized with two injections of a PGF2α analog. One day after the second injection, mares were randomly assigned to the slow-release implant (DES, 9.4mg deslorelin implant, n=6) or the control group (CON, deslorelin short-acting formulation, 1.25mg, n=6). Transrectal examination of the genital tract and collection of blood samples for the analysis of progesterone, AMH and gonadotrophins were performed until day 90 and on days of AFC assessment. AFC and follicle numbers according to size groups were determined on days 0, 10, 25, 50, 90, 180, 270 and 360 after implant insertion. The interval from implant insertion to the first spontaneous ovulation was prolonged in group DES (23.8±10.5 days) compared to CON(17.0±3.9 days) (p<0.05). Treatment influenced concentrations of LH and FSH over time (p<0.05) with the concentration of LH being greater in DES than in CON mares on days 30 and 55 and of FSH on day 15 after implant insertion, respectively (p<0.05). AMH concentration was greater in group DES from day 30 onwards (interaction treatment x time p<0.05). The AFC and the number of follicles with 5 to 10, 10 to 15 and 15 to 20 mm in diameter changed over time (p<0.05). A time x treatment interaction was demonstrated for follicles of 10 to 15 mm in diameter with more follicles of this size present in DES than in CON mares on day 90 (p<0.05). In group DES, concentration of AMH and the AFC (r=0.623, p<0.001) as well as concentration of AMH and the number of follicles 5 to 20 mm in diameter (r=0.442, p<0.01) were positively correlated whereas there was no such correlation in group CON. In conclusion, long-acting deslorelin implants induce changes in follicular development reflected in AMH plasma concentration. These changes are present from day 30 after implant insertion, suggesting that not only direct effects of deslorelin on gonadotrophin secretion but also the reduction of FSH suppressing factors from follicles such as inhibin may be involved. Treatment of mares with 9.4mg deslorelin slow-release implants might thus be a promising tool as preparation for OPU.

MP34-05 IMPACT OF NASAL, INTRAMUSCULAR, AND SUBCUTANEOUS TESTOSTERONE PELLETS ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF DATA FROM TWO RANDOMIZED CLINICAL TRIALS

You have accessJournal of UrologyCME1 May 2022MP34-05 IMPACT OF NASAL, INTRAMUSCULAR, AND SUBCUTANEOUS TESTOSTERONE PELLETS ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF DATA FROM TWO RANDOMIZED CLINICAL TRIALS Parris Diaz, Rohit Reddy, Ruben Blachman-Braun, Alexandra Dullea, Isaac J. Zucker, Daniel C. Gonzalez, Eliyahu Kresch, and Ranjith Ramasamy Parris DiazParris Diaz More articles by this author , Rohit ReddyRohit Reddy More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Alexandra DulleaAlexandra Dullea More articles by this author , Isaac J. ZuckerIsaac J. Zucker More articles by this author , Daniel C. GonzalezDaniel C. Gonzalez More articles by this author , Eliyahu KreschEliyahu Kresch More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002588.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone replacement therapy (TRT) can potentially cause decreased spermatogenesis and subsequent infertility due to decrease in intratesticular testosterone (ITT) production. Serum 17-hydroxyprogesterone (17-OHP) is a reliable surrogate for ITT that is critical for preserving male fertility. We hypothesized that long-acting T formulations will decrease ITT compared to short-acting formulations. We evaluated data from two open-label, randomized, two-arm clinical trials amongst different testosterone therapies with subcutaneous T pellets (TP), Intranasal Testosterone (NT) or Intramuscular Testosterone cypionate (TC). METHODS: A total of 75 symptomatic hypogonadal men (2 serum T <300 ng/dL drawn before 10AM) were randomized into open-label randomized clinical trials. Eligible subjects received 800mg TP, 11mg TID NT or 200 mg×2 weeks TC. Lab values were evaluated at baseline and follow-up. The primary outcome was changes in serum 17-OHP. Secondary outcome was changes in serum T. Data analyzed via Kruskal Wallis and Chi square test.Trials: NCT04439799 (June 19,2020) & NCT04523480 (August 21,2020). RESULTS: Median participant age was 45 years old, with overall baseline 17-OHP of 46 and serum testosterone of 223.5 ng/dL. Serum 17-OHP significantly decreased in all three TRT regimens (Table 1). The 4-month change in 17-OHP in the NT group (−33.3% from baseline) was less than the change seen in TC (−65.3% from baseline) or TP (−44% from baseline) (p=0.005). All T formulations increased serum testosterone levels at follow-up, with the largest increase seen in TC (+157.6%), followed by NT (+114.3%), and TP (+79.6%) (p=0.005). CONCLUSIONS: Short-acting nasal testosterone appears to decrease 17-OHP less than long-acting T formulations. All modalities saw significant increases in serum T levels at follow-up. Intranasal T and other short acting T formulations may better preserve ITT and be beneficial for hypogonadal men seeking to maintain fertility potential while on TRT. Source of Funding: Investigator Initiated Grant funded by Acerus Pharmaceuticals and Empower Pharmacy (RR). This work was also supported by National Institutes of Health Grant R01 DK130991 and Clinician Scientist Development Grant from the American Cancer Society to RR © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e580 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Parris Diaz More articles by this author Rohit Reddy More articles by this author Ruben Blachman-Braun More articles by this author Alexandra Dullea More articles by this author Isaac J. Zucker More articles by this author Daniel C. Gonzalez More articles by this author Eliyahu Kresch More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF DownloadLoading ...

Modelling Shows the Negative Impact of Age Dependent Pharmacokinetics on the Efficacy of Oxytetracycline in Young Steers.

The effect of age dependent pharmacokinetics (PK) on the clinical efficacy of oxytetracycline (OTC) against Bovine Respiratory Disease (BRD) in beef cattle was studied, using a Physiologically Based Pharmacokinetic (PBPK) model. The model includes a bodyweight dependent renal clearance. To mimic/reproduce the long terminal half-live a bone forming tissue compartment was considered. Data for the development, calibration and validation of the model were obtained from public literature. To integrate the PK with the pharmacodynamics (PD) of OTC, Monte Carlo simulations were performed using this PBPK model to predict time-concentration curves for two commonly used dosing regimens of short-acting and long-acting injectable OTC formulations in virtual populations of 5,000 steer calves of 100 kg and 400 kg. These curves were then used to calculate the value of the PKPD index for OTC, which is the ratio of the area under the concentration-time curve for 24 h (AUC24h) over the minimum inhibitory concentration (MIC) of the target pathogen (AUC24h/MIC). The MIC values were for Mannheimia haemolytica, the dose-limiting pathogen for BRD. This integration of PBPK and PD for OTC used for the treatment of BRD in calves indicated that the Probability of Target Attainment (PTA) was sufficient for efficacy in calves of 400 kg, but insufficient for calves of 100 kg, when using a long acting dosing regimen of 20 mg/kg BW, twice, with a 48-h interval. The use of a dosing regimen of 10 mg/kg BW/day for 4 days predicted sufficient PTAs in both age groups.

31.5 Clinical Considerations to Mitigate Opioid-Related Complications in Youth

Following opioid prescription, some children and adolescents are more likely to develop opioid-related complications. Although this occurrence is rare, potential detrimental effects include the development of opioid use disorder (OUD) or overdose. A recent retrospective cohort study suggests that some patient risk factors, as well as prescription characteristics, may be associated with an increased risk of opioid-related complications in the youth population. A literature review on Google Scholar and PubMed databases was conducted using the search terms “opioid related complications,” “child adolescent psychiatry,” “youth,” and “opioids” for evidence of the potential opioid-related complications that may follow an initial opioid prescription. A retrospective cohort study analysis of health insurance claims of 3.2 million youth (aged 11 to 25 years), who filled an initial opioid prescription between 2006 and 2016, reported the following findings. Within 1 year of filling their opioid prescriptions, 0.3% of patients developed OUD (0.26%) or overdosed (0.04%), with most occurring within 90 days following initial prescription. Those who experienced OUD or overdose were more likely to have comorbid mental illness diagnoses, compared to those who did not. Compared to those prescribed a short-acting formulation, patients prescribed a long-acting formulation were associated with a 159% increased risk of OUD or overdosing (adjusted risk ratio [aRR] = 2.59; 95% CI, 2.18-3.09). Daily dosing was associated with a decreased risk of OUD or overdose (aRR = 0.95; 95% CI, 0.91-0.99). Longer prescription durations were associated with increased risk of OUD and overdose (7-14 days: aRR = 1.15; 95% CI, 1.08-1.22) compared to prescriptions ≤3 days. Patients with other substance use disorders were >20 times more likely to develop these complications; 73% of them had these, of which 43.2% used nicotine, 33.4% used alcohol, and 33% used cannabis. Patients who experienced complications were more likely to be male, from an urban background, and diagnosed with a chronic pain condition. Clinicians are advised to closely follow up with youths identified as having comorbid mental health conditions or substance use disorder (SUD) to limit opioid-related complications such as overdose or OUD. Ideally, prescriptions should be for short-acting, low-dose, short-duration formulations.

MP31-08 EXOGENOUS TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME NEGATIVELY IMPACTS SPERM RETRIEVAL

You have accessJournal of UrologyInfertility: Therapy (MP31)1 Sep 2021MP31-08 EXOGENOUS TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME NEGATIVELY IMPACTS SPERM RETRIEVAL Caroline Kang, Nahid Punjani, and Peter N. Schlegel Caroline KangCaroline Kang More articles by this author , Nahid PunjaniNahid Punjani More articles by this author , and Peter N. SchlegelPeter N. Schlegel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002035.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Men with Klinefelter syndrome (KS) classically have testicular failure and are at risk for both testosterone (T) deficiency and infertility. T replacement therapy (TRT) often is initiated in adolescence for its potential neurodevelopmental benefits. Unfortunately, exogenous T has a defined adverse effect on spermatogenesis. We sought to examine the effect of exogenous T on sperm retrieval in men with KS. METHODS: All men with KS undergoing sperm retrieval by microdissection testicular sperm extraction (mTESE) performed by a single surgeon between 1995-2020 were reviewed. Demographic data and hormone-modifying agents, such as human chorionic gonadotropin (hCG) and aromatase inhibitors (AI), administered prior to mTESE were obtained. History or current use of exogenous T was recorded and categorized based on formulation into either short- (gel or foam) or long-acting (pellets or injection) groups. Descriptive statistics and SRR are reported. Patients with incomplete data on hormone therapy as well as repeat procedures on the same patient were excluded. RESULTS: A total of 290 sperm retrievals were performed on KS men during the study period. Fourteen men had a history of exogenous TRT or were currently using T at time of mTESE (Table 1). Median age was 34 years (interquartile range (IQR) 31–36), and median testis size was 1.3 mL (IQR 1.0–1.5). Five men had a remote history of TRT up to 2 years prior to mTESE, and received hCG and AI hormone therapy prior to retrieval. Of these, all five (100%) had successful sperm retrieval. In five men receiving topical testosterone and concurrent AI and/or hCG at time of mTESE, only two (40%) had successful sperm retrieval. No men receiving continuous delivery of exogenous testosterone (e.g., injectable or pellet) with concurrent hCG had sperm identified during mTESE. CONCLUSIONS: Exogenous TRT is common in KS patients. Long-acting (e.g. injectable or implantable T) therapy suppresses gonadotropin production and sperm production, predisposing men to failed sperm retrieval. However, T monotherapy with short-acting (e.g. topical) formulations together with AIs can maintain endogenous gonadotropin production and spermatogenesis; such therapy is consistent with sperm retrieval in KS men. Additional prospective trials are needed to elucidate the effects of T on sperm retrieval in KS patients. Source of Funding: CK and NP are supported in part by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e557-e558 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Caroline Kang More articles by this author Nahid Punjani More articles by this author Peter N. Schlegel More articles by this author Expand All Advertisement Loading ...

Deslorelin Slow-Release Implants Delay Ovulation and Increase Plasma AMH Concentration and Small Antral Follicles in Haflinger Mares.

Simple SummaryIn horses, oocyte collection followed by intra-cytoplasmatic sperm injection is increasingly used. The yield of oocytes is a limiting factor and depends on the number of follicles present on the ovary during oocyte collection. Therefore, the aim of this study was to analyze the effect of slow-release implants containing the GnRH analogue deslorelin on the number of follicles and on hormones regulating follicular development. Six mares received a deslorelin implant and six mares served as controls. The interval to the first spontaneous ovulation was prolonged in treated mares. The treatment changed the release pattern of the gonadotrophins LH and FSH. Changes in the number of follicles 10 to 15 mm in diameter were detected in deslorelin-treated mares. These changes were also reflected by increasing plasma anti-Muellerian hormone concentrations, a hormone produced by growing follicles. In conclusion, deslorelin implants induce changes in ovarian follicle subpopulations and could be a promising tool for the preparation of mares for assisted reproductive procedures.There is an increasing interest in the manipulation of ovarian follicular populations in large domestic animals because this could prove beneficial for assisted reproductive techniques such as ovum pick-up (OPU). The aim of the present study was to evaluate the effects of deslorelin slow-release implants (SRI) on the interovulatory interval, antral follicle count (AFC), number of follicles of different size ranges and plasma anti-Muellerian hormone (AMH) concentration in mares. To synchronize their estrous cycles, Haflinger mares (n = 12) were treated twice with a PGF2α analogue. One day after the second injection (day 0), mares received a 9.4 mg deslorelin SRI (group DES, n = 6) or 1.25 mg deslorelin in a short-acting formulation (CON; n = 6), respectively. Regular transrectal ultrasonography of the genital tract was performed and blood samples were collected for the analysis of progesterone, AMH and gonadotrophins. The interval from implant insertion to the first spontaneous ovulation was 23.8 ± 10.5 days in group DES compared to 17.0 ± 3.9 days in group CON (p < 0.05). For the concentrations of LH, FSH and AMH, interactions between time and treatment were detected (p < 0.05). The AFC and the mean number of follicles with 5 to 10, 10 to 15 and 15 to 20 mm in diameter changed over time (p < 0.05). A time x treatment interaction was demonstrated for follicles of 10 to 15 mm in diameter (p < 0.05). The changes in this follicular subpopulation were reflected by increased plasma AMH concentration in group DES. In conclusion, 9.4 mg deslorelin implants show minor effects with regard to estrus suppression in mares, whereas the changes in the subpopulation of small ovarian follicles could be a promising tool for preparation of mares for OPU.

Opioid use disorder and overdose among youth following an initial opioid prescription.

Some adolescents and young adults (termed "youth") prescribed an opioid will develop opioid use disorder or experience overdose. This study aimed to identify patient and prescription characteristics associated with subsequent risk of opioid use disorder or overdose during the year after an opioid is first dispensed. Retrospective cohort study. Commercial health insurance claims in a large United States (US) database from 2006 to 2016. Youth age 11 to 25years filling an initial opioid prescription (n=3 278 990). The primary outcome was development of an 'opioid-related complication' (a diagnosis of opioid use disorder or opioid-related overdose) during the subsequent 12months. Exposures of interest were patient (sociodemographic information, and physical and mental health diagnoses) and prescription characteristics (opioid formulation, dose, and duration). Among youth filling an initial opioid prescription, median age was 18years (interquartile range [IQR] = 16-21) and 56.1% were female. During the subsequent 12months, 10 405 (0.3%) youth experienced an opioid-related complication. Conditions associated with increased risk included mood/anxiety disorders (adjusted relative risk [aRR] = 4.45; 95% CI = 4.25-4.66) and substance use (aRR = 20.77; 95% CI = 19.74-21.84). Comorbid substance use disorders were present among 72.8% of youth experiencing an opioid-related complication and included alcohol (33.4%), cannabis (33.0%), nicotine (43.2%), and other substance use disorders (75.5%). Long-acting opioids (aRR = 2.59; 95% CI = 2.18-3.09) and longer durations were associated with increased risk (7-14days: aRR = 1.15; 95% CI = 1.08-1.22; ≥15days: aRR = 1.96; 95% CI = 1.80-2.12) compared with short-acting formulations and durations ≤3days, respectively. Among United States youth, complications after an initial opioid prescription appear to be relatively rare and appear to be associated with mood/anxiety disorders, substance use, comorbid substance use disorders, and prescriptions involving long-acting opioids or long durations.

Short-acting testosterone appears to have lesser effect on male reproductive potential compared with long-acting testosterone in mice

To compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice. In vivo mouse model. University-based basic science research laboratory. A total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the study. Exogenous testosterone was administered either in short-acting formulation (Monday-Wednesday-Friday dosing schedule, testosterone propionate 0.2 mg/kg), or long-acting formulation (3-month dosing schedule - testosterone pellets 150 mg) to male mice. Time to pregnancy, Luteinizing hormone (LH) levels, and testicular weight. Mice treated with long-acting testosterone appear to have longer time to pregnancy when compared to wild-type (33 ± 11 vs 23 ± 2.6 days, p ≤ 0.05) and mice that received short-acting testosterone propionate (26 ± 5.9 days). Mice treated with long-acting testosterone had smaller testes weight when compared to control (0.08 ± 0.01 vs 0.11 ± 0.01g; p ≤ 0.01), while the short-acting testosterone treated mice had similar testis weight when compared to control (0.09 ± 0.02 vs 0.11 ± 0.01g; ns). The serum testosterone level was elevated in mice that received testosterone pellets (285.78 ng/dL) and testosterone propionate (122.16 ng/dL) versus control (68.4 ng/dL). In mice that received long-acting testosterone pellets, LH levels at 3 months were almost undetectable while those that received short-acting testosterone remained similar to control (0.017 ± 0.058 vs 0.348 ± 0.232 IU/L; p ≤ 0.01). Female reproductive potential parameters including litter size and pup weight were collected and observed to have no difference between groups. Through a mouse breeding study, mice that received short-acting testosterone were shown to have fertility potential similar to wild-type male mice. Long-acting exogenous testosterone appeared to impair male reproductive capacity and LH levels when compared to short-acting testosterone. Short-acting testosterone appeared to cause less LH suppression. Identifying strategies to increase testosterone while simultaneously preserving male fertility is important for treating young men with hypogonadism.

Perceptions and preferences for long-acting injectable and implantable medications in comparison to short-acting medications for opioid use disorders

AimTreatment for opioid use disorders has recently evolved to include long-acting injectable and implantable formulations of medications for opioid use disorder (MOUD). Incorporating patient preferences into treatment for substance use disorders is associated with increased motivation and treatment satisfaction. This study sought to assess treatment preferences for long-acting injectable and implantable MOUD as compared to short-acting formulations among individuals with OUD. MethodsWe conducted qualitative, semi-structured telephone interviews with forty adults recruited from across the United States through Craigslist advertisements and flyers posted in treatment programs. Eligible participants scored a two or greater on the heroin or opioid pain reliever sections of the Tobacco, Alcohol, Prescription Medications, and Other Substances (TAPS) Tool, indicative of a past-year OUD. Interviews were transcribed, coded, and thematically analyzed. ResultsTwenty-four participants (60%) currently or previously had been prescribed MOUD. Sixteen participants (40%) expressed general opposition to MOUD, citing concerns that MOUD is purely financial gain for pharmaceutical companies and/or a “band aid” solution replacing one drug with another, rather than a path to abstinence. Some participants expressed personal preference for long-acting injectable (n = 16/40: 40%) and implantable formulations (n = 12/40: 30%) over short-acting formulations. About half of the participants were not willing to use injectables (n = 19/40: 48%) or implantables (n = 22/40: 55%), preferring short-acting formulations. Mixed evaluations of long- and short-acting MOUD focused on considerations of medication-related beliefs (privacy, concern over an embedded foreign body), the medication-related burden (convenience, provision of structure and support, medication administration, potential side effects), and medication-taking practices (potential for non-prescribed use, control over dosage, and duration of treatment). ConclusionsThough many participants personally prefer short-acting to long-acting MOUD, some were open to including long-acting formulations in the range of options for those with OUD. Participants felt long-acting formulations may reduce medication-related burden and the risk of diversion. Conversely, participants expressed concern about invasive administration and loss of control over their treatment. Results suggest support for expanded access to a variety of formulations of MOUD. The use of shared decision making may also help patients select the formulation best aligned with their experiences, values, and treatment goals.