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American Journal of Preventive Medicine Jun 2019Flow restrictors are child-resistant packaging innovations designed to limit the amount of liquid dispensed from a medication bottle. In 2011, flow restrictors were... (Observational Study)
Observational Study
INTRODUCTION
Flow restrictors are child-resistant packaging innovations designed to limit the amount of liquid dispensed from a medication bottle. In 2011, flow restrictors were added to pediatric liquid single-ingredient acetaminophen formulations. The hypothesis of this study is that implementation would be associated with reduced volume and severity of pediatric acetaminophen exposures reported to the U.S. National Poison Data System.
METHODS
This study describes accidental unsupervised ingestions of acetaminophen in children aged <6 years. Exposures were grouped into pre-implementation (pre-period; January 4, 2010-July 17, 2011); transition (July 18, 2011-July 15, 2012); and post-implementation (post-period; July 16, 2012-December 25, 2016) periods. Cumulative and annual rates of change per million units (i.e., bottles) sold were calculated for the pre- and post-periods for acetaminophen and pediatric liquid ibuprofen (comparator without flow restrictors). Pre- to post-period rate ratios were used to compare products and to estimate the potential effect on other over-the-counter medications. Analysis was conducted in 2017 and 2018.
RESULTS
The pre- and post-period cumulative acetaminophen exposure rate was 507.2 (95% CI=481.1, 534.6) and 325.6 (95% CI=305.8, 346.7) per 1 million units sold, respectively. Declines in the pre- versus post-period rate ratios were seen for exposures with any effect (0.642, 95% CI=0.591, 0.696) and with clinically significant outcomes (0.728, 95% CI=0.581, 0.913). In the post-period, acetaminophen exposures decreased faster than ibuprofen with a rate of change ratio of 0.936 (95% CI=0.912, 0.960) for all exposures and 0.939 (95% CI=0.909, 0.970) for exposures with any effect.
CONCLUSIONS
The addition of flow restrictors to pediatric liquid acetaminophen was associated with a reduction in the number and severity of exposures. Application of flow restrictors to other liquid medications should be considered.
Topics: Accidents; Acetaminophen; Age Factors; Antitussive Agents; Child, Preschool; Diphenhydramine; Drug Overdose; Drug Packaging; Female; Humans; Ibuprofen; Infant; Male; Nonprescription Drugs; Poison Control Centers; Seasons; United States
PubMed: 31003808
DOI: 10.1016/j.amepre.2018.12.015 -
AAPS PharmSciTech Mar 2021Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal... (Review)
Review
Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 μL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.
Topics: Drug Delivery Systems; Drug Packaging; Humans; Intravitreal Injections; Needles; Pharmaceutical Preparations; Sterilization; Syringes
PubMed: 33709236
DOI: 10.1208/s12249-021-01949-4 -
American Journal of Preventive Medicine Mar 2021In Massachusetts, recent outbreaks of HIV have been fueled by injection and sexual exposures among people who inject drugs. Understanding pre-exposure prophylaxis need,...
INTRODUCTION
In Massachusetts, recent outbreaks of HIV have been fueled by injection and sexual exposures among people who inject drugs. Understanding pre-exposure prophylaxis need, knowledge, and use among people who inject drugs will help inform and evaluate interventions.
METHODS
In 2019, investigators analyzed 2018 National HIV Behavioral Surveillance data from people who inject drugs in Boston, MA, who met eligibility criteria. Proportions of people who inject drugs with U.S. Preventive Services Task Force-based pre-exposure prophylaxis indication were estimated by types of HIV acquisition risk in the past year: injection exposure only, sexual exposure only, and overlapping injection and sexual exposures. Investigators then evaluated pre-exposure prophylaxis awareness, conversations with healthcare providers about pre-exposure prophylaxis, and self-reported pre-exposure prophylaxis use among those with and without pre-exposure prophylaxis indications.
RESULTS
The prevalence of pre-exposure prophylaxis indication was 92% overall (389/423), with 290 (69%) participants indicated for injection exposures only, 3 (<1%) indicated for sexual exposures only, and 96 (23%) indicated for both injection and sexual exposures. Among those indicated for pre-exposure prophylaxis (n=389), 152 (39%) reported being aware of pre-exposure prophylaxis, 41 (11%) had discussed pre-exposure prophylaxis with a healthcare provider, and 8 (2%) had used pre-exposure prophylaxis in the past year. There were no statistically significant differences between pre-exposure prophylaxis‒indicated and ‒nonindicated people who inject drugs with respect to pre-exposure prophylaxis awareness, discussion with a healthcare provider, and pre-exposure prophylaxis use.
CONCLUSIONS
Indication for pre-exposure prophylaxis was high, but awareness was low, conversations about pre-exposure prophylaxis with healthcare providers were uncommon, and pre-exposure prophylaxis use was extremely low. These findings highlight important areas for clinical and community-based interventions to improve pre-exposure prophylaxis uptake among and delivery to people who inject drugs.
Topics: Boston; HIV Infections; Humans; Massachusetts; Pharmaceutical Preparations; Pre-Exposure Prophylaxis; Prevalence; Substance Abuse, Intravenous
PubMed: 33229144
DOI: 10.1016/j.amepre.2020.09.011 -
Cancer Medicine Jun 2023Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment....
BACKGROUND
Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of HD-MTX-mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited.
METHODS
This cohort study included patients with newly diagnosed OGS who were treated with HD-MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD-MTX-mediated acute hepatotoxicity, co-medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD-MTX-mediated acute hepatotoxicity.
RESULTS
Almost all patients with OGS treated with HD-MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3-4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high-risk subgroups for HD-MTX-mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD-MTX. However, the concurrent use of PPIs, TMP-SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy.
CONCLUSIONS
Co-administration of PPIs, TMP-SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well-monitored and adequately pre-medicated patients with OGS undergoing chemotherapy with HD-MTX. Clinicians should pay particular attention to ALT levels when prescribing HD-MTX to children and women.
Topics: Child; Humans; Female; Methotrexate; Trimethoprim, Sulfamethoxazole Drug Combination; Cohort Studies; Osteosarcoma; Anti-Inflammatory Agents, Non-Steroidal; Proton Pump Inhibitors; Bone Neoplasms; Risk Factors; Chemical and Drug Induced Liver Injury; Disease Progression
PubMed: 37062070
DOI: 10.1002/cam4.5936 -
Applied Health Economics and Health... Sep 2023The German Pharmaceutical Market Restructuring Act (AMNOG, 2011) is a two-stage process to regulate the price of new pharmaceuticals in which price negotiations are...
OBJECTIVES
The German Pharmaceutical Market Restructuring Act (AMNOG, 2011) is a two-stage process to regulate the price of new pharmaceuticals in which price negotiations are conducted based on evidence-based medical benefit assessments using data from prior clinical trials. Although the act does not explicitly set a willingness-to-pay (WTP) threshold, the process itself implicitly establishes a WTP for health improvement. We evaluated the implicit WTP for prescription pharmaceuticals post-AMNOG in the German healthcare system from the decision-maker/payer perspective.
METHODS
We extracted data on patient-group-specific annual treatment costs and endpoints from 2011 to 2021 from the dossiers assessed by the German Federal Joint Committee (FJC; Gemeinsamer Bundesausschuss). Using incremental cost-effectiveness ratios (ICERs), we calculated a WTP for the indications (I) diabetes, (II) cardiovascular disease, and (III) psoriasis weighted according to patient group size, first from the perspective of the decision-maker (approach A), and second from the perspective of the industry (approach B). To put clinical outcome measures into relation to one another, minimum clinically important differences (MCIDs) were derived from the literature and compared.
RESULTS
The annual treatment costs of newly authorized drugs were substantially higher (both pre- and post-negotiation) than that of their comparators (e.g., psoriasis, pre-negotiation: €20,601.59, post-negotiation: €16,763.57; comparators: €5178.00). However, although newly launched drugs were more expensive than their comparators, they brought greater medical benefits and were more aligned with value (r = 0.59, P < 0.001) than older drugs. We estimated WTP to vary widely by indication group [€33,814.08 per 1 percentage point hemoglobin A1c (HbA1c) reduction for diabetes, €10,970.83 per life year gained for cardiovascular disease, and €663.46 per 1% PASI decrease for psoriasis; approach A]. WTP was converted to MCID thresholds: diabetes: €16,907.04; cardiovascular drugs: no MCID existent to convert; and psoriasis: €33,173.00. WTP remained constant over time for diabetes and cardiovascular drugs but increased for psoriasis drugs.
CONCLUSION
This paper is one of the first to estimate the implicit WTP for prescription pharmaceuticals post-AMNOG and suggests that the WTP may vary between different therapeutic areas. Additionally, making different assumptions (approach A versus approach B) with regard to the assumed effectiveness in indication areas that had been declared as having no additional benefit by the FJC may explain the different perspectives of decision-makers and of the pharmaceutical industry on the value of a pharmaceutical.
Topics: Humans; Cardiovascular Diseases; Delivery of Health Care; Germany; Health Care Costs; Pharmaceutical Preparations; Cost-Benefit Analysis
PubMed: 37249741
DOI: 10.1007/s40258-023-00815-7 -
AIDS Care Jun 2021Some women who inject drugs (WWID) would benefit from pre-exposure prophylaxis (PrEP), yet there are few studies of issues related to uptake in real-world settings. In...
Some women who inject drugs (WWID) would benefit from pre-exposure prophylaxis (PrEP), yet there are few studies of issues related to uptake in real-world settings. In this study, participants ( = 95) were offered PrEP and responded to items measuring PrEP-related attitudes, norms, and perceived behavioral control based on the Theory of Planned Behavior. We tested associations with intention to initiate PrEP and uptake. Most WWID (88%) intended to initiate PrEP and 78% accepted a prescription. Compared to WWID who did not express PrEP intentions, those who did were less concerned about attitudinal and perceived behavioral control constructs such as temporary (75% vs. 36%, = 0.01) and long-term (63% vs. 27%, = 0.05) side effects, negative interactions with their birth control (93% vs. 38%, < 0.01), their ability to take a daily pill (80% vs. 36%, < 0.01), and the cost of PrEP (87% vs. 36%, < 0.01). WWID who went on to take PrEP had fewer concerns with subjective norms constructs such as talking to health care providers about sex (91% vs. 65%, < 0.01) and drug use (88% vs. 55%, < 0.01) compared to those who did not. Attitudes and perceived behavioral control influenced intention while subjective norms had a greater impact on actual uptake.
Topics: Anti-HIV Agents; Female; HIV Infections; Humans; Intention; Pharmaceutical Preparations; Pre-Exposure Prophylaxis
PubMed: 33486981
DOI: 10.1080/09540121.2021.1874267 -
Time to reimbursement of novel anticancer drugs in Europe: a case study of seven European countries.ESMO Open Apr 2023Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer...
BACKGROUND
Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer medicines and explore factors influencing the reimbursement process in seven high-income European countries.
MATERIALS AND METHODS
We carried out a retrospective case study of anticancer medicines with European Union Market Access (EU-MA) and a positive Committee for Medicinal Products for Human Use opinion from 2016 until 2021 with subsequent national reimbursement approval (NRA). The National Health Technology Assessment (HTA) and reimbursement websites of Germany, France, UK, the Netherlands, Belgium, Norway and Switzerland were used to identify TTR, defined as time from EU-MA to NRA. Additionally, we investigated medication-, country-, indication- and pharma-related factors potentially influencing TTR.
RESULTS
Thirty-five medicines were identified for which TTR ranged from -81 days to 2320 days (median 407 days). At data cut-off, 16 (46%) were reimbursed in all seven countries. Overall, the shortest TTR was in Germany (median 3 days, all medicines reimbursed <5 days). The time limit for reimbursement of 180 days stated by the Council of European Communities after the EU-MA (EU Transparency Directive) was met for 100% of included medicines in Germany, 51% in France, 29% in the UK and the Netherlands, 14% in Switzerland, 6% in Norway and 3% in Belgium. The TTR was significantly different between countries (P < 0.001). In multivariate analysis, factors associated with shorter TTR were higher gross domestic product (GDP), absence of a pre-assessment procedure and submission by a big pharmaceutical company.
CONCLUSIONS
TTR of anticancer medicines varies significantly between seven high-income European countries and leads to inequality in access. Among explored medication-, country-, indication- and pharma-related factors we found that a high GDP, the absence of a pre-assessment procedure and submission by big pharmaceutical companies were associated with shorter TTR.
Topics: Humans; Retrospective Studies; Europe; European Union; Antineoplastic Agents; Pharmaceutical Preparations
PubMed: 37030113
DOI: 10.1016/j.esmoop.2023.101208 -
Journal of Controlled Release :... Jul 2019The physiological barriers of the eye pose challenges to the delivery of the array of therapeutics for ocular diseases. Hydrogels have been widely explored for medical... (Review)
Review
The physiological barriers of the eye pose challenges to the delivery of the array of therapeutics for ocular diseases. Hydrogels have been widely explored for medical applications and introduce possible solutions to overcoming the medication challenges of the ocular environment. While the innovations in drug encapsulation and release mechanisms, biocompatibility, and treatment duration have become highly sophisticated, the challenge of widespread application of hydrogel formulations in the clinic is still apparent. This article reviews the latest hydrogel formulations and their associated chemistries for use in ocular therapies, spanning from external anterior to internal posterior regions of the eye in order to evaluate the state of recent research. This article discusses the utility of hydrogels in soft contact lens, wound dressings, intraocular lens, vitreous substitutes, vitreous drug release hydrogels, and cell-based therapies for regeneration. Additional focus is placed on the pre-formulation, formulation, and manufacturing considerations of the hydrogels based on individual components (polymer chains, linkers, and therapeutics), final hydrogel product, and required preparations for clinical/commercial applications, respectively.
Topics: Contact Lenses, Hydrophilic; Drug Compounding; Drug Delivery Systems; Eye Diseases; Hydrogels; Lenses, Intraocular; Sterilization; Vitrectomy; Wound Healing
PubMed: 31128143
DOI: 10.1016/j.jconrel.2019.05.034 -
Biomaterials May 2020Pancreatic cancer is predicted to be the second leading cause of cancer-related death by 2025. The best chemotherapy only extends survival by an average of 18 weeks. The... (Review)
Review
Pancreatic cancer is predicted to be the second leading cause of cancer-related death by 2025. The best chemotherapy only extends survival by an average of 18 weeks. The extensive fibrotic stroma surrounding the tumor curbs therapeutic options as chemotherapy drugs cannot freely penetrate the tumor. RNA interference (RNAi) has emerged as a promising approach to revolutionize cancer treatment. Small interfering RNA (siRNA) can be designed to inhibit the expression of any gene which is important given the high degree of genetic heterogeneity present in pancreatic tumors. Despite the potential of siRNA therapies, there are hurdles limiting their clinical application such as poor transport across biological barriers, limited cellular uptake, degradation, and rapid clearance. Nanotechnology can address these challenges. In fact, the past few decades have seen the conceptualization, design, pre-clinical testing and recent clinical approval of a RNAi nanodrug to treat disease. In this review, we comment on the current state of play of clinical trials evaluating siRNA nanodrugs and review pre-clinical studies investigating the efficacy of siRNA therapeutics in pancreatic cancer. We assess the physiological barriers unique to pancreatic cancer that need to be considered when designing and testing new nanomedicines for this disease.
Topics: Gene Silencing; Humans; Nanomedicine; Nanoparticles; Pancreatic Neoplasms; Pharmaceutical Preparations; RNA Interference; RNA, Small Interfering
PubMed: 32088410
DOI: 10.1016/j.biomaterials.2019.119742 -
Molecules (Basel, Switzerland) Nov 2022Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) are in situ methods that have been applied to pre-concentrate a... (Review)
Review
A Review of In Situ Methods-Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) for the Collection and Concentration of Marine Biotoxins and Pharmaceuticals in Environmental Waters.
Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) are in situ methods that have been applied to pre-concentrate a range of marine toxins, pesticides and pharmaceutical compounds that occur at low levels in marine and environmental waters. Recent research has identified the widespread distribution of biotoxins and pharmaceuticals in environmental waters (marine, brackish and freshwater) highlighting the need for the development of effective techniques to generate accurate quantitative water system profiles. In this manuscript, we reviewed in situ methods known as Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) for the collection and concentration of marine biotoxins, freshwater cyanotoxins and pharmaceuticals in environmental waters since the 1980s to present. Twelve different adsorption substrates in SPATT and 18 different sorbents in POCIS were reviewed for their ability to absorb a range of lipophilic and hydrophilic marine biotoxins, pharmaceuticals, pesticides, antibiotics and microcystins in marine water, freshwater and wastewater. This review suggests the gaps in reported studies, outlines future research possibilities and guides researchers who wish to work on water contaminates using Solid Phase Adsorption Toxin Tracking (SPATT) and Polar Organic Chemical Integrative Sampler (POCIS) technologies.
Topics: Marine Toxins; Adsorption; Environmental Monitoring; Water Pollutants, Chemical; Organic Chemicals; Pesticides; Water; Pharmaceutical Preparations
PubMed: 36431996
DOI: 10.3390/molecules27227898