Off-label Research Articles

Off-label use of tramadol combined with Lacasera® soft drink: A sub-acute toxicological study using Wistar rats to evaluate the effects of combination on human basic haematological parameters and weight changes

Tramadol is a synthetic opioid that is used to treat moderate to severe pain in both acute and chronic conditions. Tramadol is predominantly used off-label for premature ejaculation and euphoria among male youth in Nigeria, especially when dissolved in Lacasera® soft drink, which gives it a pleasant taste. Research has not yet examined the effects of this combination on hematological parameters, despite the fact that this type of abuse is common among young people and poses a public health risk. A 28-day subacute study was conducted with Wistar rats weighing 160-180g. The rats were separated into 8 groups of 6 each. The control groups: 1 and 2 were treated with Lacasera® and deionized water respectively. Groups 3, 4 and 5 received 35mg/kg per day, 70.7mg/kg per day and 106mg/kg per day of Tramadol dissolved in deionized water respectively. Groups 6, 7 and 8 received similar doses of Tramadol dissolved in Lacasera®. Blood samples were analyzed using auto-analyzer and standard methods. The data was analyzed using a statistical tool software (SPSS version 27). All results were presented as mean ± SD. Values were considered significant at p<0.05. Hematological analysis of groups treated with Lacasera®-Tramadol combination shows dose-dependent significant decreases (p<0.05) in PCVs, RBCs, and Hbs. WBCs and platelets increased in groups that received Lacasera®-Tramadol combination. The study concludes that regular or infrequent users of Lacasera® without Tramadol are unlikely to experience serious hematological complications. However, chronic Tramadol-Lacasera® users will experience increased toxicity over time, leading to hemolytic anemia.

A Free-Floating Aortic Thrombus: An Uncommon Approach to Handle a Rare Clinical Entity.

Thrombotic material in the non-aneurysmatic and non-atherosclerotic aorta is a rare entity without any recommended standard treatment so far. We present a successful treatment strategy for patients who do not fit into any of the common approaches. A free-floating thrombus in the descending aorta was found as source of embolism in an 82-year-old female patient with lower limb ischemia. After initial heparinization of the patient without relevant reduction of the thrombotic mass, the thrombus was removed using an interdisciplinary approach. Under echocardiographic guidance to locate the thrombus, the AngioVac device, usually licensed to remove floating thrombi from the venous system, was used off-label to remove the thrombus by a transfemoral approach. To avoid rebuilding of a new thrombus, the attachment point with an exulcerated plaque in the descending aorta was covered by a stent graft via the same femoral access. The patient did not experience any further embolic events, and the postoperative course was uncomplicated. Patients with uncommon aortic diseases, such as the reported free-floating thrombus, should be treated by an individualized, interdisciplinary approach. Besides the recommended treatment options, there are other uncommon approaches that might offer an alternative in complex cases. Evidence is rare for the treatment of a free-floating thrombus in the descending aorta and the treatment strategy remains discussed controversially. We present a rather uncommon approach of successful off-label treatment for patients who do not fit into any of the common approaches (operative, endovascular, or conservative treatment based on patient's comorbidities). The AngioVac System has already been successfully used off-label in the arterial system but not in the above presented way of treating a free-floating thrombus in a patient with high embolization risk and treatment-limiting comorbidities.

How the French national authority for health assesses medicines for use in pediatrics

Children deserve to be treated with appropriate medicines based on robust assessments. Despite the introduction of new regulations, the availability of medicines for children is suboptimal because of the frequent lack of relevant clinical trials due to the difficulty of conducting such trials. Thus, the Transparency Committee (TC) of the French National Authority for Health, who oversees the assessment of medicinal products in France, set up a pediatric working group with two aims: (1) The first aim was to review all opinions on medicines for pediatric use. Out of 536 opinions delivered between 2020 and 2022, 181 (34 %) concerned medicines for pediatric use. Whereas oncology largely dominated the medicines for adults, medicines for infectious diseases, endocrinology/metabolism, neurology, and hematology mostly prevailed for children. (2) The second aim was to clarify the evaluation criteria assessed by the TC, namely, the clinical benefit (CB), the clinical added value (CAV), and the public health impact (PHI) for pediatric medicinal products. An important CB was given to 113 out of 161 (71 %) opinions on medicines for pediatric use when it concerned pathologies with a severe prognosis. The quality of the demonstration (e.g., double-blind randomized trial vs. placebo or another active medicine) played a major role in the CB level. Clinical pediatric studies were also consistently associated with higher CAV levels: levels I (major) to III (moderate) in 26 out of 42 (62 %) opinions, level IV (minor) and level V (no therapeutic progress) in 43 out of 84 (51 %) and 30 out of 43 (70 %) opinions granting a sufficient CB, respectively. Conversely, 22 out of 30 (73 %) dossiers based only on literature reviews were given a level V. The main criteria leading to the qualification of a medicine for pediatric use as providing a PHI included a significant change in the morbidity and mortality of the disease and an improvement in the care pathway. Assessments were mostly aligned on the adults in the case of subsequent extensions of indications to children. Lastly, new measures were taken aimed at shortening median delays in the assessment process in order to reduce off-label use of medicines in France.

#280 Effectiveness and safety of direct oral anticoagulants vs VKA in patients on chronic dialysis: a target trial emulation using nationwide registry data

Abstract Background and Aims The mortality and morbidity rates among patients on dialysis remain high and cardiovascular disease is the leading cause of death in this population. In chronic kidney disease (CKD), a major thromboembolic risk is paradoxically associated with a major haemorrhagic risk. Hence, the prescription of oral anticoagulants in CKD patients is challenging. Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In an exhaustive French nationwide registry of patients undergoing chronic dialysis, we compared the effectiveness and safety of off-label DOAC use versus approved vitamin K antagonist (VKA). Method Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between January 1st, 2012, and December 31st, 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using target trial emulation design, we compared the safety and effectiveness outcomes for DOAC and VKA using propensity-score-weighted cause-specific Cox regression. Results 8 954 patients received an oral anticoagulant (483 DOAC and 8 471 VKA) for the first time after the initiation of dialysis. Over a median [interquartile range] follow-up period of 1.7 [0.8-3.2] years, 2 567 patients presented a first thromboembolic event and 1 254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA (weighted hazard ratio (HR) [95% confidence interval (CI)]: 0.66 [0.46; 0.94] (Figure). A non-significant trend toward lower risk of major bleeding events was found in patients treated with a DOAC compared to patients treated with a VKA (weighted HR [95% CI]: 0.68 [0.41; 1.12]) (Figure). Sensitivity analyses showed the same trends. Conclusion The fact that patients on dialysis are excluded from large, cardiovascular-disease-focused randomized controlled trials (such as those with DOACs) significantly limits the evidence needed to make clinical decisions. Most of the retrospective cohort studies comparing these two drug classes were performed in the USA, where, in contrast to Europe, apixaban has been approved for the treatment of non-valvular fibrillation in patients on haemodialysis. Our real-world study of patients on dialysis is one of the first of its type to have assessed the effectiveness and safety of off-label DOAC prescription (relative to VKA prescription) in Europe. In a large group of dialysis patients initiating oral anticoagulation, the off-label use of DOACs was associated with a statistically significant lower risk of thromboembolic events, and a non-significant trend toward lower risk of bleeding relative to VKA use. These results are reassuring with regard to the off-label use of DOACs and might facilitate the establishment of an expert consensus and guidelines on antithrombotic therapy in patients with ESKD.

Veterinary Drug Residues in the Food Chain as an Emerging Public Health Threat: Sources, Analytical Methods, Health Impacts, and Preventive Measures.

Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a dangerous human risk. In this review, we aim to highlight the sources, occurrence, human exposure pathways, and human health effects of drug residues in food-animal products. Following the usage of veterinary medications, pharmacologically active compounds known as drug residues can be found in food, the environment, or animals. They can cause major health concerns to people, including antibiotic resistance development, the development of cancer, teratogenic effects, hypersensitivity, and disruption of normal intestinal flora. Drug residues in animal products can originate from variety of sources, including water or food contamination, extra-label drug use, and ignoring drug withdrawal periods. This review also examines how humans can be exposed to drug residues through drinking water, food, air, and dust, and discusses various analytical techniques for identifying these residues in food. Furthermore, we suggest some potential solutions to prevent or reduce drug residues in animal products and human exposure pathways, such as implementing withdrawal periods, monitoring programs, education campaigns, and new technologies that are crucial for safeguarding public health. This review underscores the urgency of addressing veterinary drug residues as a significant and emerging public health threat, calling for collaborative efforts from researchers, policymakers, and industry stakeholders to develop sustainable solutions that ensure the safety of the global food supply chain.

Drug–Drug Interactions of Hydroxychloroquine and Chloroquine in Older Patients with COVID-19 during the First Pandemic Waves: The GeroCovid Observational Study

Objective: Chloroquine (CQ) and hydroxychloroquine (HCQ) were used as off-label treatments for SARS-CoV-2 infection during the first pandemic waves. The urgency of combatting COVID-19 led to the dissemination of medical recommendations with a scarce awareness of possible drug–drug interactions. This issue primarily concerned people already taking multiple medications, such as older individuals. We estimated the prevalence of drug interactions with CQ or HCQ in COVID-19 inpatients during the first pandemic waves and their possible association with hospitalization-related outcomes. Methods: This study considers 487 patients aged ≥60, hospitalized for COVID-19 from March to December 2020, and treated with CQ or HCQ. Data on acute and chronic therapies and hospitalization length and outcomes were derived from medical records. The presence of drugs potentially interacting with CQ and HCQ was identified based on published literature and drug databases. Results: In our sample (mean age 77.1 years, 47.8% females), 255 (52.4%) patients presented with one drug interaction with CQ or HCQ, and 114 (23.4%) had more than two interactions. The most frequent drugs potentially interacting with CQ or HCQ were lopinavir/ritonavir (50.4%), azithromycin (47.2%), tocilizumab (15.4%), levofloxacin (8.7%), clarithromycin (6.0%), amlodipine (3.3%), and trazodone (2.4%). No substantial differences in the duration and outcomes of the hospitalization emerged as a function of the presence of drug–drug interactions. Conclusions: Many older patients prescribed with CQ or HCQ, which have lately proved ineffective against COVID-19, were exposed to the risk of drug–drug interaction. This underlines that medical recommendations should undergo careful peer review before being widely disseminated, even in emergencies like a pandemic.

Determining value in the treatment of activated PI3Kδ syndrome in Spain: a multicriteria decision analysis from the perspective of key stakeholders

Introduction: Activated phosphoinositide 3-kinase (PI3K)δ syndrome (APDS) is an ultra-rare inborn error of immunity (IEI) combining immunodeficiency and immune dysregulation. This study determined what represents value in APDS in Spain from a multidisciplinary perspective applying multicriteria decision analysis (MCDA) methodology. Methods: A multidisciplinary committee of nine experts scored the evidence matrix. A specific framework for orphan drug evaluation in Spain and the weights assigned by a panel of 98 evaluators and decision-makers was used. Re-evaluation of scores was performed. Results: APDS is considered a very severe disease with important unmet needs, including misdiagnosis and diagnostic delay. Current management is limited to treatment of symptoms with off-label use of therapies supported by limited evidence. Therapeutic benefit is partial, resulting in limited disease control. Haematopoietic stem cell transplantation (HSCT), the only potential curative alternative, is restricted to a reduced patient population and without evidence of long-term efficacy or safety. All options present a limited safety profile. Data on patients’ quality of life are lacking. APDS is associated with high pharmacological, medical and indirect costs. Conclusions: APDS is considered a severe disease, with limited understanding by key stakeholders of how treatment success is assessed in clinical practice, the serious impact that has on patients and the associated high economic burden. This study brings to light how MCDA methodology could represent a useful tool to complement current clinical and decision-making methods used by APDS experts and evaluators.

Activity of Cannabidiol on Ex Vivo Amino Acid Fermentation by Bovine Rumen Microbiota

Amino-acid-fermenting bacteria are wasteful organisms within the rumens of beef cattle that remove dietary amino nitrogen by producing ammonia, which is then excreted renally. There are currently no on-label uses for the control of this microbial guild, but off-label use of broad-spectrum antimicrobials has shown efficacy, which contributes to antimicrobial resistance. Plant-derived antimicrobials supplemented into the diets of cattle may offer worthwhile alternatives. This study sought to investigate the role of cannabidiol (CBD) as a terpenophenolic antimicrobial. Ex vivo cell suspensions were harvested from the rumen fluid of Angus × Holstein steers in non-selective media with amino acid substrates. The suspensions were treated with five concentrations of CBD (860 μg mL−1–0.086 μg mL−1) and incubated (24 h), after which ammonia production and viable number of cells per substrate and treatment were measured. The data demonstrated a ~10–15 mM reduction in ammonia produced at the highest concentration of CBD and negligible changes in the viable number of amino-acid-fermenting bacteria. CBD does not appear to be a biologically or economically viable terpenophenolic candidate for the control of amino acid fermentation in beef cattle.

Allergic Conjunctivitis: Review of Current Types, Treatments, and Trends.

Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells. Approximately 40% of North Americans and 20% of the world's population are impacted by some form of allergy and it continues to increase in prevalence, especially among children. Specified IgE antibodies can be found in almost all cases of exposure to seasonal or perennial allergens. Activation and degranulation of mast cells lead to increased tear levels of histamine, tryptase, leukotrienes, cytokines, and prostaglandins. The release of these factors initiates the recruitment of inflammatory cells in the conjunctival mucosa, which causes the late-phase reaction. Signs and symptoms of ocular allergies include itching, tearing, chemosis, and hyperemia, which can lead to decreased productivity and poor quality of life. Many treatment options are available to improve symptoms, including, mast cell stabilizers, antihistamines, dual-acting agents, steroids, nonsteroidal anti-inflammatory drugs (NSAIDS), and other off-label treatment modalities. This review article provides an overview of different types of allergic conjunctivitis, its pathology and immunology, and recommended methods of treatment.

Transcatheter Aortic Valve Implantation for Severe Chronic Aortic Regurgitation.

Transcatheter aortic valve implantation (TAVI) has revolutionised the management of aortic valve disease, offering a less invasive alternative to traditional surgical valve replacement for severe aortic stenosis (AS). TAVI for pure aortic regurgitation (AR) is less well established, and, in fact, it was previously labelled as a relative contraindication. However, TAVI has been utilised for selected cases of pure or predominant AR. The primary limitations regarding the use of TAVI in AR are related to the absence of anatomical factors seen in patients with AS that have contributed to the safe and stable functioning of current-generation prostheses. These include aortic root dilatation, mobile valve leaflets and labile blood pressure within the aortic root, which may further increase the risk of valve migration and periprosthetic leak after deployment. Furthermore, patients with AR have more heterogeneous aortic root anatomies when compared to the population of patients with calcific or degenerative AS. This review article describes the current evidence for the off-label use of TAVI in pure AR and the various clinical syndromes associated with AR where there may be specific challenges in the application of TAVI.

Pharmacotherapy of Hypoactive Sexual Desire Disorder in Premenopausal Women.

This review aims to provide an overview of pharmacologic management for hypoactive sexual desire disorder (HSDD) in premenopausal women, with a focus on available agents. Through a literature search on PubMed, Google Scholar, and ClinicalTrials.gov from 1999 to 2024, studies were selected using the following MeSH search terms: hypoactive sexual desire disorder, premenopause, pharmacologic management, flibanserin, bremelanotide, buspirone, bupropion, and testosterone, excluding those involving postmenopausal women or other sexual disorders. Product monographs were also reviewed. Relevant English-language studies or those conducted in humans were considered. Hypoactive sexual desire disorder, characterized by a lack of motivation for sexual activity, predominantly affects women aged 45 years and older. Treatment involves a multimodal approach, including nonpharmacologic interventions such as psychotherapy and lifestyle adjustments, alongside pharmacologic options. Although bupropion and buspirone may be considered off-label treatments, flibanserin and bremelanotide are the sole medications approved by the Food and Drug Administration for generalized acquired HSDD in premenopausal women. However, caution is advised due to their limited efficacy, potential adverse effects, and transparency issues in reporting. Hypoactive sexual desire disorder, while not life-threatening, significantly impacts well-being and relationships. Pharmacotherapy, including options like flibanserin and bremelanotide, is essential within a multidisciplinary approach. Validated tools and objective measures inform tailored premenopausal HSDD care plans and aid in striking a balance between potential risks and adverse effects while maximizing meaningful clinical benefits, including for transgender individuals. Clinicians must discern important distinctions between flibanserin, bremelanotide, and other agents when managing premenopausal HSDD. Further research with the most suitable clinical endpoints and consideration of patient factors are crucial before widespread adoption of flibanserin and bremelanotide. Pharmacists are encouraged to embrace this opportunity to provide premenopausal HSDD care in ambulatory and community practice settings.

A National Census for the Off-Label Treatment of Complex Aortic Aneurysms

A National Census for the Off-Label Treatment of Complex Aortic Aneurysms

An Assessment of Semaglutide Safety Based on Real World Data: From Popularity to Spontaneous Reporting in EudraVigilance Database

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treatment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obesity in patients with or without T2DM (liraglutide—LIR, semaglutide—SEM, and tirzepatide—TIR). Social media had an important influence on the off-label use of GLP-1 RAs for obesity, especially for SEM. We analyzed the Google queries related to SEM to assess people’s interest in this drug. We also investigated the occurrence of adverse drug reactions (ADRs) by searching the EudraVigilance database (EV) for Individual Case Safety Reports (ICSRs) that reported SEM as the suspected drug and performed a descriptive and a disproportionality analysis. The data obtained for SEM were compared to other GLP-1 RAs. SEM had the highest proportions of searches on Google associated with the term “weight loss” and presented the lowest number of severe ADRs, but it also had the highest number of ICSRs reported in EV. Even though no unexpected safety issues have been reported for it until now, SEM has a hi3gh tendency for overdose reports. The most frequent off-label use was reported for SEM and TIR. In order to lower the risks of ADRs, the off-label use should be reduced and carefully monitored.

Adverse drug reactions in paediatric surgery: prospective study on frequency and risk related factors

BackgroundPaediatric patients are especially prone to experiencing adverse drug reactions (ADRs), and the surgical environment gathers many conditions for such reactions to occur. Additionally, little information exists in the literature on ADRs in the paediatric surgical population. We aimed to quantify the ADR frequency in this population, and to investigate the characteristics and risk factors associated with ADR development.MethodsA prospective observational study was conducted in a cohort of 311 paediatric patients, aged 1–16 years, admitted for surgery at a tertiary referral hospital in Spain (2019–2021). Incidence rates were used to assess ADR frequency. Odds ratios (ORs) were calculated to evaluate the influence of potential risk factors on ADR development.ResultsDistinct ADRs (103) were detected in 80 patients (25.7%). The most frequent being hypotension (N = 32; 35%), nausea (N = 16; 15.5%), and emergence delirium (N = 16; 15.5%). Most ADRs occurred because of drug-drug interactions. The combination of sevoflurane and fentanyl was responsible for most of these events (N = 32; 31.1%). The variable most robustly associated to ADR development, was the number of off-label drugs prescribed per patient (OR = 2.99; 95% CI 1.73 to 5.16), followed by the number of drugs prescribed per patient (OR = 1.26, 95% CI 1.13 to 1.41), and older age (OR = 1.26, 95% CI 1.07 to 1.49). The severity of ADRs was assessed according to the criteria of Venulet and the Spanish Pharmacovigilance System. According to both methods, only four ADRs (3.9%) were considered serious.ConclusionsADRs have a high incidence rate in the paediatric surgical population. The off-label use of drugs is a key risk factor for ADRs development.

Pharmacovigilance Strategies to Address Resistance to Antibiotics and Inappropriate Use-A Narrative Review.

The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness, resistance, and inappropriate use of antibiotics (ABs). The terms "drug ineffective", "therapeutic failure", "drug resistance", "pathogen resistance", and "multidrug resistance" were found in PV databases and dictionaries, denoting ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. "Medication errors", especially those related to dose and indication, and "Off-label use" are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR and use are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce.

PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety.

Lipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT. We retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles. Of 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94-4.22] for mRS ≤ 3 and 0.47[0.27-0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time. Early use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies.

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients.

Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients. This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes. A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p=.370). The median (interquartile range) white blood cell (WBC) count was3.1 (2.1-5.6)at LET initiation which increased to5.1 (3.9-7.2)at the end of follow-up (p <.001). For VGCV controls, WBC was4.8 (3.4-7.2)at baseline and5.4 (3.6-7.2)at the end of follow-up; this difference was not statistically significant (p=.395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001). LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

Impact of a national audit on child and adolescent psychiatrists' prescribing practices.

A look back review of South Kerry Child and Adolescent Mental Health Services (CAMHS) in Ireland, known as the 'Maskey report' (MR), highlighted substandard prescribing practices. The aim of this 'Maskey Impact Study' (MIS) was to explore changes to child and adolescent psychiatrists' prescribing practices following the MR. The study was cross-sectional and mixed method. A study specific questionnaire was distributed electronically to psychiatrists working in CAMHS (n = 160). 102 psychiatrists participated in the study (response rate 63.8%). Perceived improvement in prescribing practices included improved medical record keeping (63.7%), consent documentation (53.9%), medication information provision (41.2%) and physical health monitoring (60.8%). However, 43.1% of psychiatrists reported a reluctance to prescribe medication even when clinically indicated and 50% were more likely to avoid off-label use. Most respondents reported increased stress levels (80.4%) with higher stress being significantly associated with reticence in prescribing (χ2 = 11.746, p < .001) and avoiding off-label use (χ2 = 15.392, p < 0.001). Thematic analysis highlighted increased medication hesitancy, enforced 'meaningless' bureaucracy and medication mistrust among families. Although improvements reported are welcomed, the increased hesitancy of medication use, avoidance of prescribing more than one medication, and avoidance of off-label use, is of concern with potential unintended adverse consequences. Reluctance in prescribing may deprive youth of access to evidence-based treatments and limit exposure of NCHDs to the safe practice of consultant-initiated psychopharmacology. Further research will be important to determine if this impacts clinical care. Continued education in psychopharmacology is essential along with increased public awareness of the evidence for medication, to help restore public confidence and trust in psychopharmacology.

Off-label use of Lumen-apposing metal stents for treatment of short benign biliary strictures

BackgroundEndoscopic stenting is the mainstay of treatment for benign biliary strictures. There is a not-negligible rate of recurrence and stent migration. Lumen-apposing metal stents (LAMS) have a unique design with short length, large diameter and wide flanges which make them less prone to migration. AimsTo describe the intraluminal use of LAMS to treat short benign biliary strictures. MethodsAll consecutive patients who underwent bi-flanged LAMS placement for benign biliary strictures, in approximately 6 years, were retrospectively included. Primary outcomes were technical and clinical success; secondary outcomes were number of endoscopic procedures, adverse events evaluation and stricture recurrence during follow-up. ResultsSeventy patients (35 male, mean age 67) were enrolled; bilio-enteric anastomotic stricture was the most common etiology. Technical and clinical success were 100 % and 85.7 %, respectively. Patients with post-surgical stricture had a higher success rate than patients with non-surgical stricture or with bilio-enteric anastomotic stricture (90.4 %, 86.3 % and 81.4 %, respectively). Adverse events were 12/70 (17.1 %): stent migration was the most frequent (8/70, 11.4 %). Stricture recurrence was found in 10/54 patients (18.5 %). ConclusionLAMS placement could be safe and effective treatment for short benign biliary strictures in patients in which a significant caliber disproportion between stricture and the duct above was revealed.

A guide to antimicrobial options for common small ruminant diseases

There are few antibiotics approved for use in small ruminant species in the United States. According to the Animal Medicinal Drug Use Clarification Act (AMDUCA), extralabel drug use may only be employed under the direction of a licensed veterinar­ian in the context of a valid veterinarian-client-patient relation­ship. However, with the implementation of FDA Guidance for Industry #263, producers will no longer have access to antibiot­ics which were previously available over the counter and could have been utilized in an extralabel manner without veterinary oversight. The aim of this discussion is to provide veterinarians with a logical approach to selecting appropriate antibiotics for use in small ruminants.