An automated process for building reliable and optimal in vitro/in vivo correlation models based on Monte Carlo simulations

Many mathematical models have been proposed for establishing an in vitro/in vivo correlation (IVIVC). The traditional IVIVC model building process consists of 5 steps: deconvolution, model fitting, convolution, prediction error evaluation, and cross-validation. This is a time-consuming process and typically a few models at most are tested for any given data set. The objectives of this work were to (1) propose a statistical tool to screen models for further development of an IVIVC, (2) evaluate the performance of each model under different circumstances, and (3) investigate the effectiveness of common statistical model selection criteria for choosing IVIVC models. A computer program was developed to explore which model(s) would be most likely to work well with a random variation from the original formulation. The process used Monte Carlo simulation techniques to build IVIVC models. Data-based model selection criteria (Akaike Information Criteria [AIC], R2) and the probability of passing the Food and Drug Administration "prediction error" requirement was calculated. To illustrate this approach, several real data sets representing a broad range of release profiles are used to illustrate the process and to demonstrate the advantages of this automated process over the traditional approach. The Hixson-Crowell and Weibull models were often preferred over the linear. When evaluating whether a Level A IVIVC model was possible, the model selection criteria AIC generally selected the best model. We believe that the approach we proposed may be a rapid tool to determine which IVIVC model (if any) is the most applicable.     

菊叶三七生物碱成分的研究

从菊科蒂叶三七植物中分离出六个生物碱,对其中四个进行了鉴定。光谱数据证明:生物碱Ⅰ和Ⅱ分别为已知的千里光碱(senecionine,Ⅰ)和千里光菲灵碱(seneciphylline,Ⅱ),生物碱Ⅲ和Ⅳ为新成分,分别命名为菊三七碱甲(sineciphyllinine,Ⅲ)和菊三七碱乙[(E)-seneciphylline,Ⅳ]。     

Epidemiological analysis of the first 1000 cases of SARS‐CoV‐2 lineage BA.1 (B.1.1.529, Omicron) compared with co‐circulating Delta in Wales,UK

BackgroundThe Omicron (lineage B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was first reported in Wales, UK, on 3 December 2021. The aim of the study was to describe the first 1000 cases of the Omicron variant by demographic, vaccination status, travel and severe outcome status and compare this to contemporaneous cases of the Delta variant.MethodsTesting, typing and contact tracing data were collected by Public Health Wales and analysis undertaken by the Communicable Disease Surveillance Centre (CDSC). Risk ratios for demographic factors and symptoms were calculated comparing Omicron cases to Delta cases identified over the same time period.ResultsBy 14 December 2021, 1000 cases of the Omicron variant had been identified in Wales. Of the first 1000, just 3% of cases had a prior history of travel revealing rapid community transmission. A higher proportion of Omicron cases were identified in individuals aged 20–39, and most cases were double vaccinated (65.9%) or boosted (15.7%). Age‐adjusted analysis also revealed that Omicron cases were less likely to be hospitalised (0.4%) or report symptoms (60.8%). Specifically a significant reduction was observed in the proportion of Omicron cases reporting anosmia (8.9%).ConclusionKey findings include a lower risk of anosmia and a reduced risk of hospitalisation in the first 1000 Omicron cases compared with co‐circulating Delta cases. We also identify that existing measures for travel restrictions to control importations of new variants identified outside the United Kingdom did not prevent the rapid ingress of Omicron within Wales.     

Tinkering and tailoring individual consultations: how practice nurses try to make cardiovascular risk communication meaningful

Aims and objectives. To explore the perspectives of practice nurses in their role of communicating cardiovascular risk to patients. Background. Nurses in primary care have for some time been engaged in cardiovascular risk discussions with patients. With the recent introduction of the NHS Health Checks, the focus on this work is set to increase. Design. Qualitative using a framework approach. Methods. Two focus groups and 16 semi-structured interviews were conducted with nurses purposively sampled from those working in primary care. Results. The nurses' accounts revealed the need to develop a relationship of trust and establish a level of relevance with each individual patient whilst discussing cardiovascular risk. Potential aspects of these discussions were as follows: working within a highly structured data-collecting task; time constraints and consideration of the individual's context. We used the idea of tailoring to describe how nurses navigate and constantly modify and pitch their approach for each patient they see in response to these constraints. Conclusion. We suggest that in order for risk to be made meaningful to patients, practice nurses recognise the need for such information to be embedded in the more reciprocal dynamics of nurse-patient consultations. From their perspective, success is often as much about not saying something, or saying it in a particular way, as saying anything accurately or consistently. Relevance to clinical practice. For practice nurses to be instrumental in the successful delivery of health prevention policy initiatives such as the NHS Health Checks, it is important to acknowledge their views and perspectives in undertaking this work. This study suggests that the nurses recognised the need for further skills and a refinement of approach for those health professionals involved.     

Group cognitive behavioural therapy for first episode psychosis: who's referred,who attends and who completes it?

Aim: Most national guidelines recommend psychological therapy for people with first‐episode psychosis (FEP) but interventions proven effective in randomized control trials (RCTs) conducted in research settings do not always translate effectively to real‐world clinical environments. In a limited health system, it is important to understand the system and patient barriers to participation in effective treatment. We sought to determine what patient characteristics influenced clinicians' decision to refer or not to refer to group cognitive behavioural therapy for FEP and what characteristics were associated with those referred attending/not attending and adhering/not adhering to the programme. Methods: Between 2006 and 2008, all cases of confirmed FEP from a defined geographical region were examined using the Structured Clinical Interview for DSM‐IV‐TR Axis I Disorders for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) diagnoses, the Scale for Assessment of Positive Symptoms, Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia and Birchwood Insight Scale. Duration of untreated psychosis was established using the Beiser Scale. Results: Of the 124 (77 males, 47 females) people in the final sample, 88 (72%) were referred for cognitive behavioural therapy (CBT), 52 (59%) attended and 12 (23%) did not complete CBT. Those with higher levels of insight into the need for treatment (U = 740.00, z = −2.63, P = 0.008) and higher levels of positive symptoms (t (120) = −3.064, P = 0.003) were more likely to be referred to CBT. Those with higher educational attainment (χ² = 9.48, P = 0.03) and fewer negative symptoms, particularly in relation to global attention (t (85) = 2.32, P = 0.03), were more likely to attend and complete CBT. Conclusion: Within an early intervention service for FEP, it appears that individuals with less education, more negative symptoms and less insight experienced significant barriers to successfully completing group CBT. More information for referring clinicians about the benefits of CBT for FEP could help increase referral rates. Assertive outreach for people at risk of disengaging or non‐adherence should also be considered.