Diphtheria-tetanus-pertussis (DTP) vaccination: understanding the perspectives and expectations of parents and healthcare professionals in France and India.

Diphtheria-tetanus-pertussis (DTP) combination vaccines are a cornerstone of infant vaccinations worldwide. DTP vaccine acceptance could be impacted by sub-optimal relationships between parents and healthcare professionals (HCPs). This survey, conducted in France and India between 14/2/2020 and 26/3/2020, aimed to understand perspectives and expectations of parents and HCPs toward DTP vaccination. Participants were parents (parents/guardians of ≤3-year-old children; France: n = 1002, India: n = 1021) and HCPs (general practitioners/pediatricians initiating DTP vaccination; France: n = 300; India: n = 300) who chose to take part. A representative sample of parents was achieved via quotas and random iterative weighting to match key demographics of the target population. In India, only parents from socio-economic classes A/B/C and private HCPs were included. Whilst DTP vaccine acceptance was high among parents in France (85%) and India (98%), French HCPs overestimated parental acceptance (99% thought parents were very/fairly accepting). The proportions of parents reporting that the HCP is someone they trust versus the proportions of HCPs wanting to be seen as trusted were discrepant in France (76% versus 90%) but not India (83% versus 85%). Some surveyed parents indicated that, ideally, they would like some input in vaccine brand decisions alongside HCPs, an opinion shared by some HCPs. In France, short-term experience post-vaccination was more important to parents than HCPs, for whom long-term protection was more important. In India, these aspects were equally important to both. Increased awareness of parents' priorities and concerns regarding DTP vaccination can support HCPs in their discussions with parents and help build trust, which may impact vaccine acceptance.

Repurposed quinacrine synergizes with cisplatin, reducing the effective dose required for treatment of head and neck squamous cell carcinoma.

Despite highly toxic treatments, head and neck squamous cell carcinoma (HNSCC) have poor outcomes. There is an unmet need for more effective, less toxic therapies. Repurposing of clinically-approved drugs, with known safety profiles, may provide a time- and cost-effective approach to address this need. We have developed the AcceleraTED platform to repurpose drugs for HNSCC treatment; using in vitro assays (cell viability, clonogenic survival, apoptosis) and in vivo models (xenograft tumors in NOD/SCID/gamma mice). Screening a library of clinically-approved drugs identified the anti-malarial agent quinacrine as a candidate, which significantly reduced viability in a concentration dependent manner in five HNSCC cell lines (IC50 0.63-1.85 µM) and in six primary HNSCC samples (IC50 ~2 µM). Decreased clonogenic survival, increased apoptosis and accumulation of LC3-II (indicating altered autophagy) were also observed. Effects were additional to those resulting from standard treatments (cisplatin +/- irradiation) alone. In vivo, daily treatment with 100 mg/kg oral quinacrine plus cisplatin significantly inhibited tumor outgrowth, extending median time to reach maximum tumor volume from 20 to 32 days (p < 0.0001) versus control, and from 28 to 32 days versus 2 mg/kg cisplatin alone. Importantly, combination therapy enabled the dose of cisplatin to be halved to 1 mg/kg, whilst maintaining the same impairment of tumor growth. Treatment was well tolerated; murine plasma levels reached a steady concentration of 0.5 µg/mL, comparable to levels achievable and tolerated in humans. Consequently, due to its favorable toxicity profile and proven safety, quinacrine may be particularly useful in reducing cisplatin dose, especially in frail and older patients; warranting a clinical trial.