Role for mannose binding lectin in the prevention of Mycoplasma infection

Polymorphisms in exon 1 of the MBL-2 gene, resulting in reduced plasma levels of mannose binding lectin, were significantly overrepresented in 23 patients with primary antibody deficiency and culture-proven mycoplasma infections (P = 0.0038). This association persisted with the inclusion of a further nine suspected (doxycycline-responsive) cases (P = 0.0087). The lectin was shown to bind to three strains of mycoplasma.     

Different Pharmaceutical Products Need Similar Terminology

In the last decade, discussions on the development of the regulatory framework of generic versions of complex drugs such as biologicals and non-biological complex drugs have attracted broad attention. The terminology used is far from harmonized and can lead to multiple interpretations of legal texts, reflection papers, and guidance documents regarding market introduction as well as reimbursement. This article describes the meaning of relevant terms in different global regions (Europe, USA, WHO) and offers a proposal for a globally accepted terminology regarding (non-) biological complex drugs.     

Pure adult-onset Spastic Paraplegia caused by a novel mutation in the KIAA0196 (SPG8) gene

SPG8 is a rare autosomal dominant hereditary spastic paraplegia (AD-HSP), with only six SPG8 families described so far. Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype. Extensive family investigation was performed after positive KIAA0196 mutation analysis, which was part of an on-going mutation screening effort in AD-HSP patients. A novel pathogenic KIAA0196 mutation p.(Gly696Ala) was identified in two AD-HSP patients, who subsequently were shown to belong to a single large Dutch pedigree with more than 10 affected family members. The phenotype consisted of a pure HSP with ages at onset between 20 and 60 years, distally reduced vibration sense in the legs in all, and urinary urgency in seven out of 10 patients. Frequent features were exercise- or emotion-induced increase of spasticity and gait problems and chronic nonspecific lower back and joint pains. We have identified a fourth pathogenic KIAA0196 mutation in a Dutch HSP-family, the seventh family worldwide, with a less severe clinical course than described before.     

The effect of intrathecal bupivacaine/morphine on quality of recovery in robot-assisted radical prostatectomy: a randomised controlled trial

Robot-assisted radical prostatectomy causes discomfort in the immediate postoperative period. This randomised controlled trial investigated if intrathecal bupivacaine/morphine, in addition to general anaesthesia, could be beneficial for the postoperative quality of recovery. One hundred and fifty-five patients were randomly allocated to an intervention group that received intrathecal 12.5 mg bupivacaine/300 μg morphine (20% dose reduction in patients > 75 years) or a control group receiving a subcutaneous sham injection and an intravenous loading dose of 0.1 mg.kg⁻¹ morphine. Both groups received standardised general anaesthesia and the same postoperative analgesic regimen. The primary outcome was a decrease in the Quality of Recovery-15 (QoR-15) questionnaire score on postoperative day 1. The intervention group (n = 76) had less reduction in QoR-15 on postoperative day 1; median (IQR [range]) 10% (1–8 [−60% to 50%]) vs. 13% (5–24 [−6% to 50%]), p = 0.019, and used less morphine during the admission; 2 mg (1–7 [0–41 mg]) vs. 15 mg (12–20 [8–61 mg]), p < 0.001. Furthermore, they perceived lower pain scores during exertion; numeric rating scale (NRS) 3 (1–6 [0–9]) vs. 5 (3–7 [0–9]), p = 0.001; less bladder spasms (NRS 1 (0–2 [0–10]) vs. 2 (0–5 [0–10]), p = 0.001 and less sedation; NRS 2 (0–3 [0–10]) vs. 3 (2–6 [0–10]), p = 0.005. Moreover, the intervention group used less rescue medication. Pruritus was more severe in the intervention group; NRS 4 (1–7 [0–10]) vs. 0 (0–1 [0–10]), p = 0.000. We conclude that despite a modest increase in the incidence of pruritus, multimodal pain management with intrathecal bupivacaine/morphine remains a viable option for robot-assisted radical prostatectomy.     

How to Regulate Nonbiological Complex Drugs (NBCD) and Their Follow-on Versions: Points to Consider

The aim of this critical review is to reach a global consensus regarding the introduction of follow-on versions of nonbiological complex drugs (NBCD). A nonbiological complex drug is a medicinal product, not being a biological medicine, where the active substance is not a homo-molecular structure, but consists of different (closely related and often nanoparticulate) structures that cannot be isolated and fully quantitated, characterized and/or described by state of the art physicochemical analytical means and where the clinical meaning of the differences is not known. The composition, quality and in vivo performance of NBCD are highly dependent on manufacturing processes of both the active ingredient as well as in most cases the formulation. The challenges posed by the development of follow-on versions of NBCD are illustrated in this paper by discussing the ‘families’ of liposomes, iron–carbohydrate (‘iron–sugar’) drugs and glatiramoids. It is proposed that the same principles for the marketing authorization of copies of NBCD as for biosimilars be used: the need for animal and/or clinical data and the need to show similarity in quality, safety and efficacy. The regulatory approach of NBCD will have to take into consideration the specific characteristics of the drugs, their formulation and manufacturing process and the resulting critical attributes to achieve their desired quality, safety and efficacy. As with the biosimilars, for the NBCD product, family-specific methods should be evaluated and applied where scientifically proven, including sophisticated quality methods, pharmacodynamic markers and animal models. Concerning substitution and interchangeability of NBCD, it is also advisable to take biosimilars as an example, i.e. (1) substitution without the involvement of a healthcare professional should be discouraged to ensure traceability of the treatment of individual patients, (2) keep an individual patient on a specific treatment if the patient is doing well and only switch if unavoidable and (3) monitor the safety and efficacy of the new product if switching occurs.     

Feasibility and Acceptability of ‘VitaVillage’: A Serious Game for Nutrition Education

Computer games have previously been used to improve nutrition knowledge in children. This paper describes the acceptability and feasibility of a serious game, “VitaVillage”, for improving child nutrition knowledge. VitaVillage is a farming-style game in which the player undertakes quests and completes questions aimed at increasing several aspects of nutrition and healthy eating knowledge. Children aged 9–12 years in two primary schools (control vs. intervention) completed a nutrition knowledge questionnaire at baseline (T1) and after 1 week (T2). Participants at the intervention school (n = 75) played VitaVillage for 20 minutes on two occasions. Control participants (n = 94) received no nutrition education. Likeability question scores and written feedback from intervention participants was reported qualitatively. Paired sample t-tests were used to compare T1 and T2 nutrition knowledge changes between control and intervention participants. Engagement with VitaVillage improved children’s overall nutrition knowledge (Mean increase of 2.25 points between T1 and T2, Standard Deviation (SD) 6.31, p = 0.035) compared to controls. The game was liked overall (mean score 77 (SD 24.6) on scale of 0–100) and positive feedback was given. Results indicate that VitaVillage has the potential to be successful as a nutrition education tool. In the future, VitaVillage’s content and gameplay will be revised, extended and evaluated for its long-term impact on eating behaviour and knowledge changes.