Antibiotics are frequently supplied without prescription in many countries. This overuse of antibiotics could facilitate the development and spread of antibiotic resistance.

Hypertension and dyslipidaemia are modifiable risk factors associated with cardiovascular diseases (CVDs) and often require a complex therapeutic regimen. The administration of several medicines is commonly associated with poor levels of adherence among patients, to which World Health Organisation (WHO) proposed a fixed-dose combination unit (polypill) as a strategy to improve adherence. In this work, we demonstrate the fabrication of patient-specific polypills for the treatment of CVDs by fused deposition modelling (FDM) 3D printing and introduce a novel solution to meet critical quality attributes. The construction of poly(vinyl alcohol) (PVA)-based polypills containing four model drugs (lisinopril dihydrate, indapamide, rosuvastatin calcium and amlodipine besylate) was revealed for the first time. The impact of tablet architecture was explored using multi-layered and unimatrix structures. The novel approach of using distilled water as a 'temporary co-plasticiser' is reported and was found to significantly lower the extruding (90°C) and 3D printing (150°C) temperatures from 170°C and 210°C respectively, with consequent reduction in thermal stress to the chemicals. XRD indicated that lisinopril dihydrate and amlodipine besylate maintained their crystalline form while indapamide and rosuvastatin calcium were essentially amorphous in the PVA tablets. From the multilayer polypills, the release profile of each drug was dependent on its position in the multilayer.In addition to the multilayer architecture offering a higher flexibility in dose titration and a more adaptive solution to meet the expectations of patient-centred therapy, we identify that it also allows orchestrating the release of drugs of different physicochemical characteristics. Adopting such an approach opens up a pathway towards low-cost multidrug delivery systems such as tablets, stents or implants for wider range of globally approved actives.

Background: Health-care workers (HCWs) are at risk of occupational exposure to bloodborne pathogens through contact with human blood and other body fluids. This study was conducted to estimate the global and regional one-year prevalence of percutaneous injuries (PCIs) among HCWs. Methods: We systematically searched EMBASE, PubMed, CINAHL and PsychInfo databases for studies published from January 2008 to January 2018 that reported the prevalence of PCIs among HCWs. A random effects meta-analysis was conducted to estimate pooled prevalence of PCIs among HCWs. Results: Of the 5205 articles identified, 148 studies from 43 countries met the inclusion criteria. The pooled global one-year prevalence estimate of PCIs was 36.4% (95% CI: 32.9-40.0). There were substantial regional variations in the one-year prevalence of PCIs, ranging from 7.7% (95% CI: 3.1-12.4) in South America to 43.2% (95% CI: 38.3-48.0) in Asia. The estimates for Africa and Europe were comparable with values of 34.5% (95% CI: 29.9-39.1) and 31.8% (95% CI: 25.0-38.5), respectively. The highest one-year prevalence by job category was among surgeons at 72.6% (95% CI: 58.0-87.2). The estimates for medical doctors (excluding surgeons), nurses (including midwives) and laboratory staff (including laboratory technicians) were 44.5% (95% CI: 37.5-51.5), 40.9% (95% CI: 35.2-46.7) and 32.4% (95% CI: 20.9-49.3), respectively. PCIs commonly occurred among HCWs working in hospital (41.8%, 95% CI: 37.6-46.0) than non-hospital (7.5%, 95% CI: 5.9-9.1) settings. Conclusion: Our findings suggest high rates of PCIs among HCWs with direct patient care across many regions of the world. However, paucity of data from some countries was a major limitation.

Polypharmacy is often needed for the management of cardiovascular diseases and is associated with poor adherence to treatment. Hence, highly flexible and adaptable systems are in high demand to accommodate complex therapeutic regimens. A novel design approach was employed to fabricate highly modular 3D printed 'polypill' capsules with bespoke release patterns for multiple drugs. Complex structures were devised using combined fused deposition modelling 3D printing aligned with hotfilling syringes. Two unibody highly modular capsule skeletons with 4 separate compartments were devised: i) concentric format: two external compartments for early release whilst two inner compartments for delayed release, or ii) parallel format: where non-dissolving capsule shells with free-pass corridors and dissolution rate-limiting pores were used to achieve immediate and extended drug releases, respectively. Controlling drug release was achieved through digital manipulation of shell thickness in the concentric format or the size of the rate limiting pores in the parallel format. Target drug release profiles were achieved with variable orders and configurations, hence confirming the modular nature with capacity to accommodate therapeutics of different properties. Projection of the pharmacokinetic profile of this digital system capsules revealed how the developed approach could be applied in dose individualization and achieving multiple desired pharmacokinetic profiles.

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