Flavour spectrum of the Puff family of disposable e-cigarettes

BackgroundIn January 2020, the US Food and Drug Administration prohibited the sale of flavours (except for menthol and tobacco) in prefilled pod devices such as JUUL to decrease youth vaping. Excluded from the prohibition were disposable devices.ObjectivesTo determine the scope and scale of flavours marketed by Puff Bar, a leading disposable brand, and related products.MethodsDisposable e-cigarette flavours were identified via online searches encompassing vendor websites, wholesale distributors, manufacturers (eg, made-in-china.com), and social media channel, Instagram, between June and August 2020.ResultsThe ‘Puff’ brand name and iconic cloud logo appear on a variety of products of differing sizes and nicotine e-liquid volumes. Among Puff Bar and its copycats (Puff-a-Likes), 139 flavours were identified. Fruit flavours predominated comprising 82.2% of the flavour varieties (fruit 50%, fruit and menthol/mint 23.6%, and fruity drinks 8.6%). A prevalent new flavour category which combines fruit with menthol/mint (Ice) was offered in 33 varieties such as Lychee Ice, Lush Ice and Banana Ice. Disposable e-cigarette brands are undertaking measures to escape tobacco regulation (eg, non-tobacco-sourced nicotine) and flavour limitations via post-market flavour additions to unflavoured nicotine e-liquid.ConclusionsThe proliferation of flavoured disposable e-cigarette products, many of which are designed to emulate popular pod devices, illustrates that narrowly limited flavour regulations covering only a single category are destined to fail. To be effective in youth protection, flavour regulations need to apply to all recreational nicotine-containing products and need to include measures to counter post-market flavour addition.

EU MDR 2017/745 will reduce the Risk of Medical Devices. Does MDCG got it Right?

Under the new European Union Medical Device Regulation (EU MDR), framed by Medical Device Coordination Group (MDCG), for each device manufacturers must have a documented risk management plan, identify and analyse the known and foreseeable hazards, estimate and evaluate the associated risks and eliminate or control those risks. In contrast with the MDD, the new EU MDR contains an explicit obligation in the new Article 10 (2), that manufacturers establish, document, implement and maintain a system for risk management. The detailed requirements of which are listed in the new Annex I Chapter I. Compared to MDD there is more emphasis on Post Market Surveillance (PMS) activities with the inclusion of European Databank or European Database for Medical Devices (EUDAMED) and mandatory submission of Periodic Safety Update Report (PSUR) to all the actors in the possession with the medical devices. A poll conducted by Aegis Lifesciences Pvt. Ltd, Ahmedabad, India concludes that the relevant annexures and sections in MDR 2017/745 have more emphasis on PMS, Vigilance, PSUR, EUDAMED, tracking, Implantation card etc. that are directed in regard to the safety of the Medical Device.

Disaggregated IPO returns, economic uncertainty and the long-run performance of SME IPOs

PurposeSmall and medium enterprises (SMEs) play a crucial role in national economies worldwide, generating employment and contributing to innovation. This study tries to investigate the performance of the newly started IPO platform for the SMEs in India through a two-staged framework developed to measure pre-market and post-market underpricing separately and the impact of economic policy uncertainty (EPU) on the IPO returns using the EPU index which is based on newspaper coverage frequency. Further, the long-run performance of SME IPOs and the factors affecting the same have also been analyzed. The two-staged framework is helpful in capturing the impact of different factors separately on the two distinctive markets and providing effective investment strategies to the investors.Design/methodology/approachA sample of 384 SME IPOs issued during 2012–2018 has been analyzed using robust regression analysis.FindingsThe study highlights the fact that there are differences in the factors affecting pre-market and post-market underpricing and reports that investors subscription rate, issue expenses, lead manager reputation and EPU are positively associated, whereas the age of the firm is negatively associated with the pre-market underpricing, and lead manager reputation positively impacts the post-market underpricing whereas issue premium and pre-market underpricing are negatively associated. Pre-market underpricing subsumes all the impact of EPU (publicly available information) in it, hence providing credence to the semi-strong market hypothesis of the Efficient Market Hypothesis (EMH). The long-run performance of SME IPOs increases with time, and lead manager reputation, pre-market and post-market underpricing are positively related to the one-year return whereas issue size, turnover and issue expense are negatively related.Originality/valueThis paper is believed to be the first attempt to analyze the performance of SME IPOs by disaggregating IPO underpricing. The findings of this study will have a great insight for the investors and policymakers.

Twelve-Month Outcomes From the Japanese Post-Market Surveillance Study of the Viabahn Endoprosthesis as Treatment for Symptomatic Peripheral Arterial Disease in the Superficial Femoral Arteries

Purpose: To assess the midterm safety and effectiveness of the Gore® Viabahn® Endoprosthesis as treatment for symptomatic peripheral arterial disease (PAD) in the superficial femoral arteries (SFA). Materials and Methods: A prospective, multicenter, post-market surveillance study was conducted in Japan. Patients with symptomatic SFA lesions ≥ 10 cm and reference vessel diameters ranging from 4.0 to 7.5 mm were eligible for enrollment; patients with traumatic or iatrogenic vessel injury in the thoracic, abdominal, or pelvic arteries were excluded. Outcomes evaluated at 12 months were primary patency (PP), primary-assisted patency (PAP), secondary patency (SP), freedom from target lesion revascularization (fTLR), occurrence of device- or procedure-related serious adverse events (SAEs), and stent fractures. Results: From August 2016 to May 2017, 321 patients were enrolled at 64 Japanese sites (mean age, 73.9±8.7 years; 77.3% male). Hypertension, diabetes, and end stage renal disease were present in 84.4%, 54.8%, and 23.1% of patients, respectively. Mean lesion length was 23.6 cm±6.6 cm, with lesions ≥ 15 cm in 271 patients (84.4%). TASC C/D lesions accounted for 86.6% (39.1% TASC C, 47.5% TASC D); 26.5% had critical limb ischemia. Baseline ABI was 0.60±0.16. A total of 562 devices were implanted in 324 limbs, with a majority of patients (68.8%) receiving 2 stents. Through 12 months, 92.1% of patients were evaluable. Kaplan-Meier-estimated PP, PAP, and SP at 12 months was 85.6%, 91.7%, and 94.8%, respectively. Twelve-month fTLR was 92.3%. Mean change in ABI at 12 months was 0.343±0.21; mean improvement in Rutherford class was 2.5. Device- or procedure-related SAEs occurred in 3.1% through 30 days, with a majority of early SAEs consisting of access complications. Through 12 months, a cumulative 10.6% had device- or procedure-related SAEs, with the most common being device occlusions in 4.0%. Lower limb amputation occurred in 0.9% and was related to pre-existing ulceration or gangrene in all 3 cases. No stent fractures were observed at 12-month x-ray evaluation. Conclusion: In a real-world Japanese patient population characterized by long SFA lesions and complex PAD, the Viabahn endoprosthesis was associated with excellent patency rates through 12 months and an acceptable safety profile.

Vagus nerve stimulation therapy in people with drug-resistant epilepsy (CORE-VNS): rationale and design of a real-world post-market comprehensive outcomes registry

IntroductionThe Vagus Nerve Stimulation Therapy System (VNS Therapy) is an adjunctive neuromodulatory therapy that can be efficacious in reducing the frequency and severity of seizures in people with drug-resistant epilepsy (DRE). CORE-VNS aims to examine the long-term safety and clinical outcomes of VNS in people with DRE.Methods and analysisThe CORE-VNS study is an international, multicentre, prospective, observational, all-comers, post-market registry. People with DRE receiving VNS Therapy for the first time as well as people being reimplanted with VNS Therapy are eligible. Participants have a baseline visit (prior to device implant). They will be followed for a minimum of 36 months and a maximum of 60 months after implant. Analysis endpoints include seizure frequency (average number of events per month), seizure severity (individual-rated categorical outcome including very mild, mild, moderate, severe or very severe) as well as non-seizure outcomes such as adverse events, use of antiseizure medications, use of other non-pharmacological therapies, quality of life, validated measures of quality of sleep (Pittsburgh Sleep Quality Index or Children’s Sleep Habit Questionnaire) and healthcare resource utilisation. While the CORE-VNS registry was not expressly designed to test hypotheses, subgroup analyses and exploratory analysis that require hypothesis testing will be conducted across propensity score matched treatment groups, where possible based on sampling.Ethics and disseminationThe CORE-VNS registry has already enrolled 823 participants from 61 centres across 15 countries. Once complete, CORE-VNS will represent one of the largest real-world clinical data sets to allow a more comprehensive understanding of the management of DRE with adjunctive VNS. Manuscripts derived from this database will shed important new light on the characteristics of people receiving VNS Therapy; the practical use of VNS across different countries, and factors influencing long-term response.Trail registration numberNCT03529045.

Profil Peredaran Obat Disfungsi Ereksi Ilegal

Tren temuan obat ilegal yang beredar di Indonesia terus mengalami peningkatan dari tahun 2008 – 2018. Pada periode tersebut, obat golongan kelas terapi disfungsi ereksi menjadi data yang mendominasi dengan frekuensi temuan paling banyak. Hal ini juga diperkuat oleh data Public Warning BPOM dan laporan Post Market Alert System tahun 2015 – 2017 dimana pada periode tersebut obat tradisional mengandung bahan kimia obat golongan disfungsi ereksi marak ditemukan. Penyusunan penelitian ini dilakukan dengan metode kualitatif dan kuantitatif dengan tujuan untuk mengidentifikasi situasi peredaran (termasuk pengguna), menggambarkan potensi nilai peredaran obat disfungsi ereksi ilegal di Indonesia, dan potensi penyimpangan distribusi bahan baku obat disfungsi ereksi. Penelitian dilakukan pada 8 (delapan) kota di Indonesia, yaitu Jabodetabek, Serang, Padang, Bandung, Semarang, Surabaya, Bali, dan Samarinda. Hasil penelitian menunjukkan bahwa peredaran obat disfungsi ereksi secara luring melalui kios permanen/lapak/gerobak di Indonesia masih banyak ditemukan dan peredaran obat disfungsi ereksi secara daring juga mengalami peningkatan dengan adanya perluasan pasar melalui website, media sosial, dan e-commerce. Profil pengguna obat golongan disfungsi ereksi berada pada kelompok usia produktif (30 – 45 tahun) dengan tingkat penghasilan antara Rp 2.000.000,- hingga Rp 4.000.000,- serta merk yang paling banyak dikonsumsi adalah Viagra. Potensi diversi peredaran bahan baku obat disfungsi ereksi terjadi pada proses importasi bahan baku dan penyaluran dari masing – masing PBF/importir kepada industri farmasi.

Reinforcing Collaboration and Harmonization to Unlock the Potentials of Advanced Therapy Medical Products: Future Efforts Are Awaited From Manufacturers and Decision-Makers

Some advanced therapy medicinal products (ATMPs) hold great promises for life-threatening diseases with high unmet needs. However, ATMPs are also associated with significant challenges in market access, which necessitates the joint efforts between all relevant stakeholders to navigate. In this review, we will elaborate on the importance of collaborations and harmonization across different stakeholders, to expedite the market access of promising ATMPs. Manufacturers of ATMPs should proactively establish collaborations with other stakeholders throughout the whole lifecycle of ATMPs, from early research to post-market activities. This covered engagements with (1) external developers (i.e., not-for-profit organizations and commercial players) to obtain complementary knowledge, technology, or infrastructures, (2) patient groups and healthcare providers to highlight their roles as active contributors, and (3) decision-makers, such as regulators, health technology assessment (HTA) agencies, and payers, to communicate the uncertainties in evidence package, where parallel consultation will be a powerful strategy. Harmonization between decision-makers is desired at (1) regulatory level, in terms of strengthening the international standardization of regulatory framework to minimize discrepancies in evidence requirements for market authorization, and (2) HTA level, in terms of enhancing alignments between regional and national HTA agencies to narrow inequity in patient access, and cross-border HTA cooperation to improve the quality and efficiency of HTA process. In conclusion, manufacturers and decision-makers shared the common goals to safeguard timely patient access to ATMPs. Collaboration and harmonization will be increasingly leveraged to enable the value delivery of ATMPs to all stakeholders.

PBPK Modeling and Simulation and Therapeutic Drug Monitoring: Possible Ways for Antibiotic Dose Adjustment

Pharmacokinetics (PK) is a branch of pharmacology present and of vital importance for the research and development (R&D) of new drugs, post-market monitoring, and continued optimizations in clinical contexts. Ultimately, pharmacokinetics can contribute to improving patients’ clinical outcomes, helping enhance the efficacy of treatments, and reducing possible adverse side effects while also contributing to precision medicine. This article discusses the methods used to predict and study human pharmacokinetics and their evolution to the current physiologically based pharmacokinetic (PBPK) modeling and simulation methods. The importance of therapeutic drug monitoring (TDM) and PBPK as valuable tools for Model-Informed Precision Dosing (MIPD) are highlighted, with particular emphasis on antibiotic therapy since dosage adjustment of antibiotics can be vital to ensure successful clinical outcomes and to prevent the spread of resistant bacterial strains.