Back to basics: measuring the impact of interventions to limit the spread of COVID-19 in Europe.

BACKGROUND: Following the emergence of the COVID-19 pandemic in Europe at the start of 2020, most countries had implemented various measures in an attempt to control the spread of the virus. This study analyses the main non-pharmaceutical interventions and their impact on the rate by which cumulative cases and deaths were growing in Europe during the first wave of this pandemic. METHODS: The interventions analysed are the school closures, restrictions on travel, cancellation of events, restrictions on gatherings, partial and full lockdowns. Data was collected on the implementation date of these interventions, and the number of daily cases and deaths during the first wave of the pandemic for every country and territory geographically located in Europe. The study uses growth rates to calculate the increase in cumulative cases and deaths in Europe before, during, and after these interventions were implemented. RESULTS: The results show that decisions to close schools, cancel events, and restrict travel were taken during the same time period, whereas the decisions for the other interventions were taken when the growth rates were similar. The most effective interventions at lowering the rate by which cumulative cases were increasing were the travel restrictions, school closures, and the partial lockdown, while most effective against cumulative deaths were the partial lockdown, travel restrictions, and full lockdown. CONCLUSION: All the interventions reduced the rate by which cumulative cases and deaths were increasing with the partial lockdowns being the most effective from the other interventions, during the first wave of the pandemic in Europe.

A review of electronic medical records and safe transfusion practice for guideline development.

BACKGROUND AND OBJECTIVES: Electronic medical records (EMRs) are often composed of multiple interlinking systems, each serving a particular task, including transfusion ordering and administration. Transfusion may not be prioritized when developing or implementing electronic platforms. Uniform guidelines may assist information technology (IT) developers, institutions and healthcare workforces to progress with shared goals. MATERIALS AND METHODS: A narrative review of current clinical guidance, benefits and risks of electronic systems for clinical transfusion practice was combined with feedback from experienced transfusion practitioners. RESULTS: There is opportunity to improve the safety, quality and efficiency of transfusion practice, particularly through decision support and better identification procedures, by incorporating transfusion practice into EMRs. However, these benefits should not be assumed, as poorly designed processes within the electronic systems and the critically important electronic-human process interfaces may increase risk while creating the impression of safety. CONCLUSION: Guidelines should enable healthcare and IT industries to work constructively together so that each implementation provides assurance of safe practice.

ICH Q3D Drug Product Elemental Risk Assessment: The Use of An Elemental Impurities Excipients Database.

The purpose of this publication is to show how an elemental impurities excipient database can be used in assisting the execution of a drug product elemental impurities risk assessment as required by the ICH Q3D guidelines. As a result of this exercise, we have demonstrated that the database, used in conjugation with other sources of information, is a credible source of elemental impurity levels in excipients therefore, a valuable source of information in completion of drug product risk assessments. This useful collection of data helps to reduce the burden of analytical testing for elemental impurities in excipients.

Managing emerging mutagenicity risks: Late stage mutagenic impurity control within the atovaquone second generation synthesis.

The mutagenic-impurity control strategy for a second generation manufacturing route to the non-mutagenic antipneumocystic agent atovaquone (2-((1R,4R)-4-(4-chlorophenyl)cyclohexyl)-3-hydroxynaphthalene-1,4-dione) 1 is described. Preliminary assessment highlighted multiple materials of concern which were largely discharged either through returning a negative bacterial mutagenicity assay or through confidence that the impurity would be purged during the downstream processing from when it was first introduced. Additional genotoxicity testing highlighted two materials of concern where initial assessment suggested that testing for these impurities at trace levels within the drug substance would be required. Following a thorough review of process purging detail, spiking and purging experimentation, and an understanding of the process parameters to which they were exposed an ICH M7 Option 4 approach could be justified for their control. The development of two 1H NMR spectroscopy methods for measurement of these impurities is also described as well as a proposed summary table for describing the underlying rationale for ICH M7 control rationales to regulators. This manuscript demonstrates that process purging of potential mutagenic impurities can be realised even when they are introduced in the later stages of a process and highlights the importance of scientific understanding rather than relying on a stage-counting approach.

An Elemental Impurities Excipient Database: A Viable Tool for ICH Q3D Drug Product Risk Assessment.

To support the practical implementation of the International Council for Harmonisation (ICH) Q3D guideline, which describes a risk-based approach to the control of elemental impurities in drug products, a consortium of pharmaceutical companies has established a database to collate the results of analytical studies of the levels of elemental impurities within pharmaceutical excipients. This database currently includes the results of 26,723 elemental determinations for 201 excipients and represents the largest known, and still rapidly expanding, collection of data of this type. Analysis of the database indicates good coverage of excipients relevant to real-world drug product formulations and tested element profiles consistent with ICH Q3D recommendations. The database includes the results from multiple analytical studies for an excipient and thus incorporates within it an indication of both excipient supplier and batch-to-batch variability as well as any variability associated with the different testing organizations and methods employed. The data confirm the findings of earlier smaller studies that elemental impurity concentrations in excipients are generally low and when used in typical proportions in formulated drug products are unlikely to pose a significant patient safety risk. The database is now in active use as one line of evidence in ICH Q3D risk assessments.

The prevalence of urogenital micro-organisms detected by a multiplex PCR-reverse line blot assay in women attending three sexual health clinics in Sydney, Australia.

This study used a previously described multiplex PCR-based reverse line blot (mPCR/RLB) assay to assess the prevalence and distribution of 14 urogenital pathogens or putative pathogens, namely Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma parvum, Ureaplasma urealyticum, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, herpes simplex virus types 1 and 2, and human adenovirus. First-voided urine specimens and endocervical and self-collected vaginal swabs from each of 216 women attending three sexual health clinics in Sydney, Australia, were tested and the results were compared with those of reference methods for each organism. One hundred and sixty-eight women (77.7 %) had at least one and 105 (48.6 %) had more than one target organism, most commonly G. vaginalis and Ureaplasma spp. The prevalence of each of the four known sexually transmissible pathogens was <5 %. Of the 216 women, 111 (51.4 %) reported at least one symptom consistent with genital or urethral infection, including discharge, pain or discomfort. Only G. vaginalis was detected more frequently in women with symptoms (P = 0.05). The specificity of the mPCR/RLB assay compared with that of the reference methods for each organism and for all specimen types was 100 %. The mean sensitivities of the mPCR/RLB assay compared with those of the reference methods for self-collected vaginal swabs, cervical swabs and first-voided urine specimens for all organisms were 99.3, 98.1 and 84.6 %, respectively; however, these differences were not significant. There were no differences in sensitivities between specimen types for C. trachomatis, N. gonorrhoeae, T. vaginalis and H. influenzae, although all were found infrequently. Overall, the mPCR/RLB platform was found to be an accurate testing platform in a sexual health clinic setting.

Improved expression of secreted and membrane-targeted proteins in insect cells.

Secretory and membrane-bound proteins are generally produced in lower amounts in insect cells compared with cytoplasmic and nuclear proteins. There may be many reasons for this, including degradation of recombinant proteins by proteases, competition for cellular resources between native and recombinant proteins, and physical blockage of the secretory pathways. In the present study, we describe the construction of a baculovirus in which chiA (chitinase) and cath (cathepsin) genes have been deleted and show improved recombinant protein expression using this vector. We confirmed the complete removal of both genes by PCR, restriction enzyme analysis and enzyme assays, and the modified virus DNA was shown to be stable in bacterial cells over multiple passages. A selection of recombinant genes were inserted into the double-deletion virus and their expression levels compared with recombinant viruses that had single or no gene deletions. In all instances, the double-deletion viruses showed greatly enhanced levels of protein production for both secreted and nuclear/cytoplasmic proteins. In summary, we have conclusively demonstrated the importance of this deletion vector for the high-level production of recombinant proteins.

GP treatment decisions for patients with depression: an observational study.

BACKGROUND: GPs are prescribing more antidepressants than previously, but not in accordance with guidelines. The reasons why they prescribe are not well understood. AIM: To explore associations between GP treatment and severity of depression, patients' life difficulties, previous history of illness and treatment, and patient attitudes. DESIGN: Observational study in two phases, 3 years apart. SETTING: Seven practices in Southampton, UK. METHOD: Adult attenders who consented were screened for depression in the waiting room. After the consultation, the 17 participating GPs completed questionnaires on the perceived presence and severity of depression, patients' life difficulties, previous problems and treatment, patient attitudes towards antidepressants, and their treatment decisions. Patients returned postal questionnaires on sociodemographics, life events, physical health, and attitudes towards antidepressants. RESULTS: Of 694 patients screened in the two phases, the GPs rated 101 (15%) as depressed, acknowledged depression in 44 cases (6%), and offered treatment in 27 (4%), including antidepressants in 14 (2%). Offers of antidepressants were more likely in both phases where the GPs rated the depression as moderate rather than mild, and where they perceived a positive patient attitude to antidepressants. However, GP ratings of severity did not agree well with the validated screening instrument, and their assessments of patients' attitudes to treatment were only moderately related to patients' self-reports. CONCLUSIONS: In line with current guidelines, GPs base prescribing decisions on the perceived severity of depression, taking patients' preferences into account, but they do not accurately identify which patients are likely to benefit from treatment. Better ways to assess depression severity and patient attitudes towards antidepressants are needed in order to target treatment more appropriately.