US Generic Antiseizure Medication Supply Chain: Observations from Analysis of US Government Databases.

BACKGROUND: Generic drug manufacturing has shifted away from the U.S. in the last few decades. The medication supply chain, from manufacturers to resellers, has become increasingly globalized and complex. This has led to bottlenecks in their manufacture resulting in medication shortages. Review of this process as it pertains to antiseizure medications (ASM) shows gaps in our comprehension of its complexities. Understanding these processes will be essential for preventing medication shortages. OBJECTIVES: The aim of this research is to examine the generic ASM supply with an emphasis on production, labeling, and repackaging. METHODS: Data from the United States Food and Drug Administration (FDA) and the National Library of Medicine (NLM) website DailyMed was used to evaluate supply chain details to gather information on antiseizure medication formulations, manufacturing locations, and labeling. RESULTS: Out of 3142 ASM-related active National Drug Code (NDC-9) codes, 2663 NDC-9 codes with Abbreviated New Drug Application (ANDA) status were included in the analysis. Most (94.8 %) were enteral, with only 5.2 % being parenteral (intravenous and intramuscular route). We identified the manufacturing country for 82 % of these codes, corresponding to 306 unique ANDA numbers. 119 manufacturing sites in 12 countries produce generic ASM Finished Dosage Forms (FDF): 103 for enteral and 21 for parenteral. India is the main producer of enteral ASM FDFs with 49 sites, followed by the US with 36. Regarding parenteral formulation, five countries had 21 unique manufacturing locations. 42 % of the 103 enteral ASM FDFs manufacturing sites produced multiple ASM FDFs, with one facility making eight distinct ASMs. 34.4 % of facilities were associated with over 3 ANDAs, and 15.1 % with more than 5. 22.7 % of ANDAs lacked a manufacturing facility identifier. Repackaged ASM FDFs constituted 48 % of NDC-9 s. Gabapentin and pregabalin were the most common oral ASMs. CONCLUSIONS: India is the major source for generic ASM FDFs manufacturing, leading to concerns about overall supply dependency on that country. There is a paucity of facilities for the global supply of parenteral ASM FDFs. There is missing data for many NDC-9 codes emphasizing urgency for transparency in the supply chain.

Preventing depression among older people living in rural areas: A randomised controlled trial of behavioural activation in collaborative care.

OBJECTIVES: This study aimed to test if a behavioural activation (BA) programme was more effective than usual care at reducing the risk of conversion to major depression over 52 weeks among adults aged 65 years or older living in rural Western Australia. Secondary aims were to test if participants assigned to the BA intervention experienced greater decline in the severity of depressive and anxiety symptoms than older adults treated with usual care over 26 and 52 weeks, as well as greater improvement in physical and mental health-related quality of life. METHODS: Randomised controlled clinical trial that started recruitment in February 2016 in rural Western Australia. We used the electoral roll to invite adults aged 65 years or over living in suitable regions of Western Australia to take part in the study. We recruited those who consented and screened positive to at least one of the two Whooley questions: feeling down/depressed/hopeless or little interest or pleasure over the past month. Participants were randomly assigned to usual care or usual care plus a phone-delivered BA program (1:1). The intervention consisted of a self-managed BA program supported by three 45-min phone sessions delivered by a BA therapist over a period of 8 weeks. We used the DSM-5 criteria to establish the presence of a major depressive episode, and Patient Health Questionnaire, Generalised Anxiety Disorder Scale and SF-36 to assess symptoms of depression, anxiety and quality of life. RESULTS: Of the 309 older adults randomised, 307 started the trial: 153 usual care and 154 BA (computer-generated random permuted even blocks ranging in size from 8 to 20). Six participants developed a major depressive episode during follow-up, four of them in the usual care group (odds ratio of depression associated with the intervention = 0.49, 95% CI = 0.04, 3.49-blind assessment). Seventy-three (23.8%) participants were lost over 52 weeks-there were no differences between usual care and intervention group. Intention-to-treat analyses using mixed regression models found modest non-significant effects of the BA intervention, while complete-case analyses showed that participants treated with BA compared with usual care experienced significant improvements in depression and anxiety symptoms over 52 weeks, as well as improved mental health quality of life. CONCLUSIONS: Few participants developed a major depressive episode during follow-up. The BA intervention was associated with improved symptoms of depression and anxiety, although the clinical significance of these benefits remains unclear.

Behavioural activation in nursing homes to treat depression (BAN-Dep): study protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Depression is a common disorder among older people living in residential aged care facilities. Several trials have demonstrated the effectiveness of behavioural therapies in treating depressive symptoms in older adults living in the community and in residential aged care. Behavioural Activation is demonstrably effective even when delivered by non-specialists (staff without formal psychological training), although strategies for adapting its use in residential aged care facilities are yet to be explored. This study will determine whether training residential care staff in the use of a structured Behavioural Activation programme is more effective at decreasing depressive symptoms among older residents than internet-based training about depression recognition and management alone. METHOD AND ANALYSIS: The behavioural activation in nursing homes to treat depression (BAN-Dep) trial is a pragmatic two-arm parallel clustered randomised controlled trial. It will recruit 666 residents aged 60 or older from 100 residential aged care facilities, which will be randomly assigned to the Behavioural Activation or control intervention. Staff in both treatment groups will be encouraged to complete the Beyondblue Professional Education to Aged Care e-learning programme to improve their recognition of and ability to respond to depression in older adults. Selected staff from intervention facilities will undergo additional training to deliver an 8-module Behavioural Activation programme to residents with subthreshold symptoms of depression-they will receive ongoing Mental support from trained Behavioural Activation therapists. Outcome measures will be collected by blind research officer at baseline and after 3, 6 and 12 months. The Patient Health Questionnaire-9 is the primary outcome measure of the study. ETHICS AND DISSEMINATION: The trial will comply with the principles of the Declaration of Helsinki for Human Rights and is overseen by the University of Western Australia (reference RA/4/20/4234) and Melbourne Health (reference number HREC/18/MH/47) Ethics Committees. The results of this research project will be disseminated through publications and/or presentations in a variety of media to health professionals, academics, clinicians and the public. Only de-identified group data will be presented. TRIAL REGISTRATION: ACTRN12618000634279.

Complex care core curriculum for pediatric post-graduate trainees: Results of a North American needs assessment.

PURPOSE: There are increasing numbers of children with chronic, complex conditions requiring comprehensive care, however post-graduate training in this field is limited. Lack of training may contribute to reticence in engaging with their care. Although children with medical complexity (CMC) are heterogeneous, their care needs are similar. We aimed to address a lack of explicit training via a standardized curriculum. As an initial step, a collaborative needs assessment of key content was developed. METHODS: An on-line survey with drafted learning objectives was sent to professionals skilled in complex care. Participants indicated if an objective should be obtained by the end of Junior residency (PGY2), Senior residency (PGY4), or not at all. RESULTS: Eighty-two Canadian and US professionals participated; 60.3% practiced in a University Health Centre and 60% cared for CMC and participated in pediatric postgraduate education. Over 80% felt that the medical home concept should be understood by the end of PGY2, and that trainees should develop a care plan by the end of PGY4. CONCLUSION: This needs assessment supported the learning objectives and provided information on the expected competency time line for knowledge and skill acquisition. Additional comments will be used to revise the objectives.

Cost-effectiveness of epinephrine and dexamethasone in children with bronchiolitis.

OBJECTIVE: Using data from the Canadian Bronchiolitis Epinephrine Steroid Trial we assessed the cost-effectiveness of treatments with epinephrine and dexamethasone for infants between 6 weeks and 12 months of age with bronchiolitis. METHODS: An economic evaluation was conducted from both the societal and health care system perspectives including all costs during 22 days after enrollment. The effectiveness of therapy was measured by the duration of symptoms of feeding problems, sleeping problems, coughing, and noisy breathing. Comparators were nebulized epinephrine plus oral dexamethasone, nebulized epinephrine alone, oral dexamethasone alone, and no active treatment. Uncertainty around estimates was assessed through nonparametric bootstrapping. RESULTS: The combination of nebulized epinephrine plus oral dexamethasone was dominant over the other 3 comparators in that it was both the most effective and least costly. Average societal costs were $1115 (95% credible interval [CI]: 919-1325) for the combination therapy, $1210 (95% CI: 1004-1441) for no active treatment, $1322 (95% CI: 1093-1571) for epinephrine alone, and $1360 (95% CI: 1124-1624) for dexamethasone alone. The average time to curtailment of all symptoms was 12.1 days (95% CI: 11-13) for the combination therapy, 12.7 days (95% CI: 12-13) for no active treatment, 13.0 days (95% CI: 12-14) for epinephrine alone, and 12.6 days (95% CI: 12-13) for dexamethasone alone. CONCLUSION: Treating infants with bronchiolitis with a combination of nebulized epinephrine plus oral dexamethasone is the most cost-effective treatment option, because it is the most effective in controlling symptoms and is associated with the least costs.