A review of the characteristics and treatment progress of 45 pregnant opiate addicts attending the Irish National Drug Advisory and Treatment Centre over a two year period.

The increase in the number of patients presenting to the National Drug Advisory and Treatment Centre addicted to opiates has been accompanied by an increase in the number of pregnant opiate addicts attending for treatment. Studies published in January 1982 referred to the emergence of maternal addiction as a serious problem in Ireland. Since then the escalation of this specific problem has continued and a programme designed to meet the needs of the pregnant addict was initiated at the clinic. This paper reviews the characteristics and treatment progress of 45 opiate addicts who were referred to the clinic over a two year period

An expedient strategy for the diversity-oriented synthesis of macrocyclic compounds with natural product-like characteristics

Naturally-derived macrocyclic compounds are associated with a diverse range of biological activities, including antibacterial effects, and there are over 100 marketed macrocycle drugs derived from natural products. However, synthetic macrocycles are widely considered to be poorly explored in antibiotic development (indeed, within drug discovery in general). This has been attributed to challenges associated with the generation of such compounds. Whilst there are synthetic methods that can produce large collections of structurally similar macrocycles (i.e., compounds with varying appendages based around similar core macrocyclic ring architectures) there is a relative dearth of strategies for the efficient generation of more structurally diverse macrocycle collections in which there is greater variation in the nature of macrocyclic scaffolds present. Such macrocycle collections should contain compounds with a broad range of biological activities (including antibacterial activities) and the requisite robust synthetic methodology useful for analogue synthesis and lead optimization once an active compound has been identified in a biological screen. Herein, we describe a new and expedient diversity-oriented synthesis (DOS) strategy for the generation of a library of novel structurally diverse macrocyclic compounds with a high level of scaffold diversity. The strategy is concise, proceeds from readily-available starting materials, is modular in nature and features a variety of macrocyclisation techniques. In this proof-of-concept study, the synthesis of several previously unreported macrocyclic compounds was achieved. Each of these macrocycles was based around a distinct molecular scaffold and contained natural product-like structural features (e.g., three-dimensionality and multiple hydrogen bond donors and acceptors) as well as synthetic handles for potential further elaboration. The successful generation of these macrocycles demonstrates the feasibility of the new DOS strategy as a synthetic platform for library generation.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no [279337/DOS]. In addition, the group research was supported by grants from the Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Medical Research Council and Welcome Trust

3D positioning of ACL attachment sites during flexion

It is essential when performing anterior cruciate ligament (ACL) reconstruction that the replacement ligament has sufficient mechanical properties to function during all activities. In order to mechanically test a synthetic ligament and assess how well it will function, it is necessary to know how the device will be loaded both axially and in torsion for different activities. We have developed a novel method by which the 3D movement of ACL attachment sites can be calculated from standard MRI data; which can then, in turn, be processed to estimate torsional and tensional loading data. The 3D shape of an individual patient knee was determined from standard MRI images using image segmentation techniques. The knee was then moved into position for each degree of flexion (ranging from -10deg to 140deg). The positions were known from published interventional MRI data which has recorded bone positions of ten healthy patients during flexion when weight bearing. Finally, the locations of the attachment sites throughout flexion were determined and the torsional and tensional loading within the synthetic ligament calculated. The ligament data were analysed assuming that the synthetic ligament was implanted at 90deg of flexion without pre-tension.The results demonstrated significant twisting during hyperextension of the synthetic ligament (maximum 95.5deg), which would result in an approximate torsional force of 3.9N and a torque of 0.01Nm. This correlates with previous work by Zavatsky et al. which examined the mechanics behind ligament twisting [1]. Maximum ligament elongation (3.46mm) was found at 50deg of flexion, which would represent axial loading of 336N. For the calculations the synthetic ligament was assumed to be comparable to the native ACL, with a stiffness of 97Nmm-1[2], diameter 6mm and shear modulus 0.00172GPa. This study highlights the importance of considering both ligament twist as well as elongation when testing synthetic ligaments for ACL reconstruction. Some in vivo trials of synthetic ACL replacement devices have found fibre wear to be an issue; it is possible that cyclic torsional loading tests could have predicted these problems.[1] Zavatsky et al. J Eng Med (1994) 208 p229[2] Hosseini et al. J Orthop Sci (2009) 14 p29

Socio-economic variations in anticipated adverse reactions to testing HPV positive: Implications for the introduction of primary HPV-based cervical screening

Some cervical cancer screening programmes are replacing cytology with human papillomavirus (HPV) DNA testing as the primary screening test. Concerns have been previously raised around the potential psychosocial impact of testing positive for HPV. We analysed socio-economic variations in anticipated adverse reactions to testing positive for HPV in women of screening age in the general population. A questionnaire was mailed to a random sample of 5553 women aged 20-64 in 2010, selected through primary care in Ireland. This included questions on: socio-economics; HPV knowledge; and women's anticipated adverse psychosocial responses to testing HPV positive (shame, anxiety, stigma and worry). Multivariable linear regression was used to identify socio-economic factors significantly associated with each anticipated adverse reaction. The response rate was 62% (n = 3470). In multivariate analyses, having only attained primary level education were significantly associated with higher mean scores for all four adverse outcomes. Religion was significantly associated with all four adverse outcomes. Age was associated with anxiety and worry; younger women (<30 years) had the highest mean scores. Being married/cohabiting was significantly associated with significantly lower shame and worry scores. Not working was significantly associated with higher mean anxiety and worry scores. Our large population-based survey found significant socio-economic variations in anticipated adverse reactions to testing HPV positive. In order to minimise possible negative impacts on screening uptake and alleviate potential adverse psychological effects of HPV-based screening on women, screening programmes may need to develop specific messages around HPV infection and HPV screening that target certain subgroups of women

Artificial Anterior Cruciate Ligament (ACL) Reconstruction for more Natural Knee Kinematics

Aim:The aims of this study were to define the design criteria of an artificial ACL which could reproduce the non-linear load-elongation characteristics of the native ACL, and to investigate the mechanical behaviour of a novel ACL reconstruction design consisting of a metallic elastic system and a polymeric cord.Introduction:Kinematic and survivorship studies on the ACL intact and ACL deficient knees have emphasised the importance of preserving and/or reconstructing the ACL [1], [2]. The unique mechanical properties of the ACL and the non-linear relationship between the ACL forces and the quadriceps muscle forces at different flexion angles are the key elements in providing normal kinematics.Current synthetic ACL reconstruction grafts have shown poor long-term results, mainly due to wear, creep, fatigue and mechanical failure. None of the synthetic and biological grafts used for the ACL reconstruction have been able to replicate the normal mechanical behaviour of the ACL and prevent degenerative disease progression such as osteoarthritis.Method:Desired mechanical properties of the artificial ACL were defined based the results of in vitro and in vivo biomechanical studies. Suitable materials were found for the prosthetic ACL which met the required design criteria. Implicit finite element analyses were performed on a spring-cord construct design and the output force-elongation data compared to the estimated in-vivo natural ACL properties found in the literature.Results:It was shown that an artificial ACL should have a non-linear stiffness with low resistance to the initial load (~30 Nmm-1 stiffness in the toe region) and increased stiffness under higher load (~110 Nmm-1 stiffness in the linear region). Suitable materials for the ACL reconstruction design (i.e. CoCrMo alloy and UHMWPE fibres) were identified based on their biocompatibility, strength, strain, creep and fatigue propertiesThe FEA results showed that the mechanical properties of the novel artificial ACL deisgn closely resembled that of the natural ACL at 30° of flexion. A validation test was performed on prototype samples, which supported the finite element data.ConclusionsThe non-linear force-elongation properties of the native ACL can be reproduced by an artificial ACL reconstruction system in the ACLD knees

REFERQUAL: A pilot study of a new service quality assessment instrument in the GP Exercise Referral scheme setting

Background The development of an instrument accurately assessing service quality in the GP Exercise Referral Scheme (ERS) industry could potentially inform scheme organisers of the factors that affect adherence rates leading to the implementation of strategic interventions aimed at reducing client drop-out. Methods A modified version of the SERVQUAL instrument was designed for use in the ERS setting and subsequently piloted amongst 27 ERS clients. Results Test re-test correlations were calculated via Pearson's 'r' or Spearman's 'rho', depending on whether the variables were Normally Distributed, to show a significant (mean r = 0.957, SD = 0.02, p < 0.05; mean rho = 0.934, SD = 0.03, p < 0.05) relationship between all items within the questionnaire. In addition, satisfactory internal consistency was demonstrated via Cronbach's 'α'. Furthermore, clients responded favourably towards the usability, wording and applicability of the instrument's items. Conclusion REFERQUAL is considered to represent promise as a suitable tool for future evaluation of service quality within the ERS community. Future research should further assess the validity and reliability of this instrument through the use of a confirmatory factor analysis to scrutinise the proposed dimensional structure

Trends in, and predictors of, anxiety and specific worries following colposcopy: a 12-month longitudinal study

Objective Little is known about which women are at greatest risk of adverse psychological after-effects following colposcopy. This study examined time trends in, and identified predictors of, anxiety and specific worries over 12 months. Methods Women attending two hospital-based colposcopy clinics for abnormal cervical cytology were invited to complete psychosocial questionnaires at 4, 8 and 12 months following colposcopy. General anxiety and screening-specific worries (about cervical cancer, having sex and future fertility) were measured. Generalised estimating equations were used to assess associations between socio-demographic, lifestyle and clinical variables and risk of psychological outcomes. Results Of 584 women initially recruited, 429, 343 and 303 completed questionnaires at 4, 8 and 12 months, respectively. Screening-specific worries declined significantly over time but were still relatively high at 12 months: 23%, 39% and 18% for worries about cervical cancer, fertility and having sex, respectively. Anxiety remained stable (20%) over time. Risks of cervical cancer worry and anxiety were both almost double in women without private health insurance (cervical cancer worry: OR = 1.80, 95% CI 1.25–2.61; anxiety: OR = 1.84, 95% CI 1.20–2.84). Younger women (<40 years) had higher risk of fertility worries. Non-Irish women had higher risk of anxiety (OR = 2.13, 95% CI 1.13–4.01). Conclusions Screening-specific worries declined over time but anxiety remained stable. Notable proportions of women still reported adverse outcomes 12 months following colposcopy, with predictors varying between outcomes. Women in socio-demographically vulnerable groups were at greatest risk of adverse psychological outcomes. This information could inform development of interventions to alleviate psychological distress post-colposcopy. Copyright © 2015 John Wiley & Sons, Ltd