BACKGROUND: In 2005, the Food and Drug Administration issued a black box warning regarding increased mortality and cardiovascular accidents with the off-label use of antipsychotic medication (APM) in patients with dementia. To improve the quality of care for patients with dementia in nursing homes (NH), in early 2012, the Centers for Medicare & Medicaid Services launched the National Partnership (NP) aimed at combatting the excessive use of APM. Within five years of the partnership, the number of antipsychotic prescriptions in NHs decreased by 34%. The objective of the present study was to examine how APM use has impacted other outcomes, including mortality and major cardiovascular events such as stroke and myocardial infarction (MI) among NH residents with dementia.
METHODS: We analyzed Medicare data on a sample of 611,773 long-term NH residents with dementia, aged 50 years and older, from 2011 through 2016. Residents who had received hospice care during the time period were excluded. Cross-sectional (by year) logistic regressions were conducted to examine the associations of APM use with death, stroke, and MI in the years 2011-2016. Regression models were adjusted for demographic and co-morbidity indicators.
RESULTS: Logistic regressions (see results in Table 1) revealed that NH residents prescribed APM had a significantly higher probability of death compared to non-users from 2011 through 2015. However, in 2016, the probability of death was lower among APM users than non-users, although the association was weak. Additionally, NH residents who were on APM were less likely to have a stroke or MI than non-users from 2011 through 2016.
CONCLUSIONS: Current study findings suggest that APM use is likely associated with a heightened probability of death among long-term NH residents, which is consistent with previous literature. The finding that APM use is negatively associated with stroke and MI is inconsistent with prevailing understandings that APM use would lead to higher risks of these outcomes. The shift in the likelihood of death in 2016, and negative associations with stroke and MI warrant further investigation as to the possible contributing factors of death and cardiovascular events in NH residents on antipsychotic medications.

Most new drugs are not labeled for certain populations, such as infants and children; and \"off-label\" use of drugs is common in pediatric patients. In this article, the author introduces pediatricians to the services of compounding pharmacists. He discusses topical anesthetic combinations, laxative formulations, medications for attention-deficit hyperactivity disorder, antinausea medications, diaper-rash medications, acne medications and head -ice medications. He concludes that the compounding pharmacist must use innovative thinking to formulate pediatric titrations of adult medications and to flavor those titrations to make them more palatable for children.

OBJECTIVE: Some individuals are using drugs to try to enhance cognitive and social-affective functioning and asking physicians for off-label prescriptions for neuroenhancement (e.g., stimulants). Several medical societies released guidance on prescribing neuroenhancers, some of which refer to potential societal effects of neuroenhancement (e.g., distributive justice), besides risks and benefits to users. Which institutions (e.g., medical societies, government, universities) should make decisions on allowing neuroenhancement and whether they should consider potential societal effects are unclear. We examined whether and how much support for allowing pharmaceutical neuroenhancers was influenced by the institution and potential individual and societal effects of neuroenhancers.
METHODS: We conducted a discrete-choice experiment using a constructed representative sample of the US adult public. Multinomial logit models were used to analyze the data.
RESULTS: Participants (n = 927) demographically resembled the US population. Risks of serious side effects (OR 0.20, CI 0.18-0.22) and a lack of benefits for users (OR 0.31, CI 0.26-0.38) had the largest negative effect on participants\' support for allowing neuroenhancers. A risk of mild side effects had a moderate negative effect on participants\' support for allowing neuroenhancers (OR 0.67, CI 0.62-0.74) and the prospect of more meaningful, long-lasting benefits for users a moderate positive effect (OR 1.74, CI 1.61-1.87). Positive or negative effects of neuroenhancers on the average well-being of people in society and on equality had moderate effects on participants\' support for allowing neuroenhancers. For example, the odds of participants\' support for allowing enhancers with a negative effect on societal well-being were around half (OR 0.45, CI 0.40-0.50) and the odds of allowing enhancers that worsen inequality were approximately 40% lower compared with enhancers without such effects (OR 0.62, CI 0.55-0.71). The odds of participants allowing neuroenhancers were slightly (10%) lower if enhancers reduced users\' authenticity (OR 0.90, CI 0.84-0.97). The institution regulating neuroenhancers and neuroenhancers providing users with an unfair advantage did not affect participants\' decisions.
CONCLUSIONS: When presented with both individual and societal considerations, the public seems to support medical societies and other institutions making policy decisions about neuroenhancers based on risks and benefits for users, as well as, but to a lesser extent, effects on equality and societal well-being.

UNASSIGNED: The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME).
UNASSIGNED: All patients with n-AMD and DME treated in the maintenance phase according to the \"treat and extend\" strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events.
UNASSIGNED: Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported.
UNASSIGNED: In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator.
UNASSIGNED: This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.

暂无摘要。

OBJECTIVE: To characterize the response and survival outcomes of yttrium-90 transarterial radioembolization (90Y-TARE) for unresectable, liver-dominant metastases from primary neoplasms other than colorectal carcinoma.
METHODS: This study included 1474 patients enrolled in the RESiN registry who received resin 90Y-TARE as part of their oncologic management for unresectable primary or secondary liver tumors (NCT02685631). 33% (481/1474) were treated for liver metastases of non-colorectal origin (m-nonCRC), compared to 34% (497/1474) treated for colorectal liver metastases (mCRC) and 34% (496/1474) treated for hepatocellular carcinoma (HCC). Treatment response and cancer survival probabilities were computed and compared for each primary cancer type. The Kaplan-Meier method and log-rank test were used to compare survival outcomes.
RESULTS: Radiological responses were observed in 12 unique cancer types, mostly heavily pre-treated malignancies refractory to multiple lines of systemic therapies. The overall use of resin 90Y-TARE in m-nonCRC resulted in better treatment outcomes in terms of duration of response, progression free survival, time to progression and overall survival (P = 0.04, P = 0.02, P = 0.01, P = 0.04). Analyses of cancer cell types revealed that metastatic neuroendocrine tumor, sarcoma, and ovarian, renal, prostate, and breast cancers were associated with superior treatment outcomes, whereas worse treatment outcomes were observed in metastatic lung, gastric, pancreatic and esophageal cancers.
CONCLUSIONS: Real-world data demonstrate the use of resin 90Y-TARE in m-nonCRC refractory to standard chemotherapy. For some cell types, this expanded use achieved superior treatment outcomes relative to the reference standard of mCRC, suggesting the need for inquiry into broadened indications for 90Y-TARE.

NTX is FDA-approved for opiate and alcohol use disorders as anti-craving agent. It has been used successfully off-label in other psychiatric indications. Here, we shed some light on these while examining the extant evidence.

Metformin is best known as a foundational therapy for type 2 diabetes but is also used in other contexts in clinical medicine with a number of emerging and potential indications. Many of its beneficial effects may be mediated by modest effects on weight loss and insulin sensitivity, but it has multiple other known mechanisms of action. Current clinical uses beyond type 2 diabetes include: polycystic ovarian syndrome; diabetes in pregnancy/gestational diabetes; prevention of type 2 diabetes in prediabetes; and adjunct therapy in type 1 diabetes. As metformin has been in clinical use for almost 70 years, much of the underpinning evidence for its use in these conditions is, by definition, based on trials conducted before the advent of contemporary evidence-based medicine. As a result, some of the above-established uses are \'off-label\' in many regulatory territories and their use varies accordingly in different countries. Going forward, several current \'repurposing\' investigational uses of metformin are also being investigated: prevention of cancer (including in Li Fraumeni syndrome), renal protection, Alzheimer\'s disease, metabolic dysfunction-associated steatotic liver disease and promotion of healthy ageing. Despite the longevity of metformin and its important current roles beyond type 2 diabetes in clinical medicine, it has further potential and much research is ongoing.

BACKGROUND: Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications.
METHODS: We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections.
RESULTS: Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients\' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6).
CONCLUSIONS: Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.

The interleukin-6 (IL-6) pathway plays a crucial role in various rheumatic diseases. Tocilizumab, a biologic targeting IL-6 receptor, has been widely used in clinical practice, though it\'s officially approved in China for only three indications. To address clinical challenges associated with the off-label use of tocilizumab in treating rheumatic diseases, the Committee of Chinese Primary Health Care Foundation for Rheumatologists and Immunologists engaged multidisciplinary experts and highlight 12 related clinical issues. We aggregated the drug specifications, the guidelines for clinical management of rheumatic diseases and the evidence from clinical research. Recommendations were formed through voting with the consensus conference method incorporating the Oxford evidence-based medicine criteria to evaluate the strength of evidence and recommendations. We have formulated 10 recommendations for off-label use of tocilizumab related to giant cell arteritis, polymyalgia rheumatica, Takayasu arteritis, systemic sclerosis, adult-onset Still\'s disease, rheumatoid arthritis, and juvenile idiopathic arthritis. This consensus aims to provide references for the rational use of tocilizumab in clinical practice and enhance pharmacovigilance monitoring.
白细胞介素-6（IL-6）通路参与多种风湿性疾病，靶向IL-6受体的生物制剂托珠单抗临床使用广泛，但在国内仅获批3种适应证。为规范临床托珠单抗超说明书用药治疗风湿性疾病，中国初级卫生保健基金会风湿免疫学专业委员会组织国内相关专业的专家就调研的12个临床问题，检索国内外药品说明书、风湿性疾病指南共识及临床研究等证据，采用牛津大学循证医学中心分级系统进行证据评价和推荐强度分级，并经共识专家组讨论、投票，最终形成10条推荐意见，涉及巨细胞动脉炎、风湿性多肌痛、大动脉炎、系统性硬化病、成人斯蒂尔病、类风湿关节炎和幼年特发性关节炎，旨在为临床医师提供合理用药依据并为药学部门管理提供参考。.