Pharmacokinetics of albuterol and butorphanol administered intravenously and via a buccal patch

Conventional routes of drug administration have several disadvantages. The rate and extent of absorption can vary greatly depending on the drug, its formulation, the presence or absence of food, drug interactions, and the pH of gastrointestinal fluids. Extensive first-pass metabolism can greatly reduce the absorption of many drugs. Better dosage forms or drug delivery mechanisms could minimize some of these problems. The pharmaceutical industry has recognized the need for, and has developed many new, novel drug delivery systems. Drugs that previously experienced diminished effective concentrations due to the first-pass effect may now be given by a novel route. The dosing frequency of many drugs may be reduced when administered by a novel route or site. Transmucosal drug delivery (TMDD) via the buccal mucosa is one site that is suited to rapid drug absorption and systemic delivery. Drugs selected for TMDD must have physiochemical properties that will allow them to penetrate the mucosa and produce therapeutic blood concentrations. This study utilized a buccal patch less than 1.5 cm in length to deliver albuterol and butorphanol-two drugs with dissimilar physiochemical properties. The purpose of this study was to establish pharmacokinetic parameters and the bioavailability of albuterol and butorphanol when administered intravenously and buccally. Three dogs weighing at least 20 kg were studied using a randomized crossover design, each receiving albuterol and butorphanol by buccal and intravenous administration. Blood samples were collected and analyzed using ELISA. Values for pharmacokinetic parameters were analyzed using compartmental and non-compartmental models. For albuterol, extrapolated Cmax and Co after buccal and IV administration were 10.28 ± 2.77 and 57.74 ± 9.04 ng/ml, respectively. Volume of distribution at steady state (Vss) was 2.13 ± 1.30 L/kg and Cl was 4.73 ± 3.91 ml/min/kg. A significant difference existed between the disappearance rate constant of buccal and intravenous albuterol administration. The disappearance half-lives of buccal and IV albuterol were 160.96 ± 24.19 and 364.20 ± 115.20 min, respectively. The bioavailability of buccally administered albuterol was 35%. Maximal concentration (Cmax) and Co after buccal and IV butorphanol administration were 6.66 ± 1.65 and 8.24 ± 5.55 ng/ml, respectively. Volume of distribution at steady state (Vss) was 27.58 ± 10.14 L/kg and Cl was 137.87 ± 19.55 ml/min/kg. The half-life of buccally administered butorphanol was 259.15 ± 33.12 min and the half-life of IV butorphanol was 172.12 ± 94.95 min. The bioavailability of buccally administered butorphanol was 606%. The buccal patch used in this study achieved systemic concentrations for both albuterol and butorphanol. Further studies are needed to determine if therapeutic drug concentrations can be achieved with the buccal patch and if the patch can result in clinical efficacy

Why don’t young women go for Chlamydia testing? A qualitative study employing Goffman’s stigma framework

Many women who might be at risk of having the sexually transmitted infection(STI) Chlamydia trachomatis either delay going, or do not go, for testing. Weaimed to examine the factors that either prevent or discourage Irish young women from going for Chlamydia testing. We conducted in-depth interviews with 35 women in the Republic of Ireland who were between 18 and 29 years of age. Accounts were analysed using Goffman’s stigma framework. Study respondents strongly associated Chlamydia and Chlamydia testing with stigma and felt that only irresponsible, promiscuous risk takers were at risk of contracting the infection. Respondents saw themselves as responsible, moral actors who avoided risk and took good care of their bodies; they were therefore not at risk of having Chlamydia. Going for Chlamydia testing was seen as a risky activity that could shift respondents identities into a negative ‘Other’ category. Respondents feared that if they found themselves in this ‘Other’ category they would open themselves to bullying and ostracism. While a negative act from a medical perspective, for respondents the act of not testing was seen as a positive activity that helped to reinforce their identities as good, ‘worthy’ individuals and avoided negative social consequences that might otherwise arise from the testing process

Chlamydia Screening in Ireland: a pilot study of opportunistic screening for genital Chlamydia trachomatis infection in Ireland (2007-2009). Economic evaluation

Economic Evaluation The aim of the economic evaluation was to examine the cost effectiveness of the two screening models tested in the Chlamydia Screening in Ireland Pilot (CSIP) study: (a) Clinical Setting screening, and (b) ’Pee-in-a-pot’ periodic screening in third level institution/college settings. The methodological approach comprised of a dynamic transmission model paired with an economic model. In both analyses, screening was compared to a control strategy of no organised screening, that is existing care in Ireland. A public health system or provider perspective was adopted with respect to costs. The analysis considered the cost of screening to the health service, and the costs of infection and complications, not any additional costs reported by young people in accepting a chlamydia screening test. Health outcomes were assessed in terms of major outcomes (MOs) averted and quality adjusted life years (QALYs) gained. The costs of Clinical Setting screening were presented in terms of the cost per offer (€26 ), the cost per negative case (€66), the cost per positive case (€152), and the cost per partner notified and treated (€74). The costs of ’Pee-in-a-pot’ screening were presented in terms of the cost per negative case (€39), the cost per positive case (€125), and the cost per partner notified and treated (€74). In both analyses, screening was estimated to result in fewer major outcomes, fewer QALYs lost, and higher healthcare costs compared to the control strategy. The incremental cost effectiveness analyses indicated that screening in the Clinical Setting would result in an incremental cost per MO averted of €6,093 and an incremental cost per QALY gained of €94,717. ’Pee-in-a-pot’ screening was estimated to result in incremental cost effectiveness ratios of €2,294 per MO averted and €34,486 per QALY gained respectively. In Ireland, there is no fixed and generally agreed cost effectiveness threshold below which health care technologies would be considered by policy makers to be costeffective. Nonetheless, on the basis of other technologies that are currently funded, it is not likely that screening delivered in the Clinical Setting, given an incremental cost per QALY in the region of the €94,717 found in this study, would be considered cost effective. ’Pee-in-a-pot’ screening in third level institution/college settings may be considered cost effective if a cost effectiveness threshold in the region of €45,000 per QALY gained is used. This is open to question, however, given the current economic climate and its resulting impact in terms of imposing further constraints on future healthcare budgets. It is also important to note that this strategy would have minimal in impact in reducing overall chlamydia prevalence in the population, if not supported by general population screening and prevention strategy

Chlamydia Screening in Ireland: a pilot study of opportunistic screening for genital Chlamydia trachomatis infection in Ireland (2007-2009). Summary Integrated Report

Genital Chlamydia trachomatis (CT) infection is the most common curable, bacterial sexually transmitted infection (STI) worldwide [1, 2]. The number of cases notified in Ireland increased from 3,353 in 2005 to 5,781 in 2009 [3]. Notifications have increased since 2004 when legislation requiring laboratory notification came into effect. Chlamydia is usually a ‘silent’ asymptomatic infection, spread without the knowledge of those transmitting and contracting it: most cases remain undetected and thus untreated. It is a major public health problem because it causes pelvic inflammatory disease (PID) in up to 30% of infected women who are not treated, which can lead to ectopic pregnancy and tubal factor infertility, and it also facilitates the transmission of HIV in both women and men [1, 4]. Prevalence studies in Ireland have detected chlamydia in 4–11% of young people [5, 6, 7], with positivity rates of over 10% in some settings [8]. Similar rates have been found in large studies in the United Kingdom (UK) [9], elsewhere in Europe [10] and North America [11]. A 2004 review estimated UK rates of 4–5% for women under 20 years in the general population, and 8–17% in women under 20 years attending sexual health services [9]. The authors of the review assumed, in the absence of data, that males had similar rates. Age under 25 years is considered a risk factor for infection in England [12]. In the English National Chlamydia Screening Programme (NCSP) overall chlamydia positivity rates have averaged 7.6% in men and 9.3% in women, based on a total of 370,012 screening tests reported [13]. Chlamydia screening has become more feasible due to the development of urinebased laboratory tests, which can be used in clinical and non-clinical settings, instead of more invasive and uncomfortable methods such as endocervical and urethral swabs. Urine testing is now the norm for screening men for chlamydia. For these reasons and because most cases are asymptomatic and undetected, especially in women, several countries have introduced chlamydia screening interventions [1]. A 2005 report prepared by the Health Protection Surveillance Centre (HPSC) [14] concluded that an investigation of the feasibility, acceptability and likely uptake of chlamydia screening in various settings in Ireland should be prioritised. It also concluded that agreement on best practice for the management of identified infections and partner notification was urgently needed. Following a competitive tendering process in late 2006, the HPSC, supported by the Health Research Board (HRB), contracted a team of population health and other specialists from the Royal College of Surgeons in Ireland (RCSI), the National University of Ireland Galway (NUIG) and the Health Service Executive (HSE) to conduct a pilot study of chlamydia screening.The study ran from 2007 to 2009. Since 2009, several articles and reports have been published internationally, including reviews and the results of screening studies, which question the case for chlamydia screening in the general population. A systematic review of screening programmes concluded that the available evidence did not justify the establishment of opportunistic chlamydia screening programmes in under-25 year olds in the general population, given methodological weaknesses in the trials cited as justification for screening [4]. A review of the three phases of the English National Chlamydia Screening Programme (NCSP) reported screening coverage levels in the target population of only 4.8% in 2007–2008 [13]; although by 2009–2010, 47% of sexually active young women and 25% of men had been tested [15]. A review by the English National Audit Office [16] concluded that the NCSP had not demonstrated value for money, citing lack of efficiencies in purchasing and logistics. Also, models had shown that annual testing rates of young people of between 26% and 43% would be needed in order to significantly reduce the prevalence of chlamydia [17]. The recent higher coverage levels achieved by the NCSP in reaching these recommended levels is a cause for optimism, and valuable lessons will be learned from the English national programme. However, the potential of opportunistic chlamydia screening to prevent serious morbidity (chiefly pelvic inflammatory disease in women) has been challenged by the results of an important randomised control trial of screening among young female students in London [18]. The trial found that most episodes of PID (30 of 38) would not have been prevented by annual screening as they occurred in women who had tested negative for chlamydia at the start of the 12 months

Chlamydia Screening in Ireland: a pilot study of opportunistic screening for genital Chlamydia trachomatis infection in Ireland (2007-2009). Screening Intervention Report

This report summarises the findings of the Pilot Screening Intervention conducted in Ireland between 2008 and 2009 as part of the Chlamydia Screening in Ireland Pilot study. The studies aimed to pilot screening models and to evaluate their feasibility and effectiveness. The study was commissioned by the Health Protection Surveillance Centre (HPSC) and overseen by the Health Research Board (HRB). It was carried out by a team from the Division of Population Health Sciences at the Royal College of Surgeons (RSCI) in Ireland, the College of Medicine, Nursing and Health Sciences at the National University of Ireland Galway, and Consultants in Public Health Medicine from the Health Service Executive (HSE). ² Ethical approval for study components was provided by Research Ethics Committees of the RCSI, NUI Galway and the Irish College of General Practitioners (ICGP)

Young women's decisions to accept chlamydia screening: influences of stigma and doctor-patient interactions

<p>Abstract</p> <p>Background</p> <p>An understanding of the factors that encourage young women to accept, and discourage them from accepting, STI (sexually transmitted infection) testing is needed to underpin opportunistic screening programs for the STI <it>Chlamydia trachomatis </it>(opportunistic screening involves healthcare professionals offering chlamydia tests to people while they are attending health services for reasons that are usually unrelated to their sexual health). We conducted a qualitative study to identify and explore: how young women would feel about being offered opportunistic tests for chlamydia?; how young women would like to be offered screening, and who they wanted to be offered screening by?; and what factors would influence young women's partner notification preferences for chlamydia (who they would notify in the event of a positive diagnosis of chlamydia, how they would want to do this).</p> <p>Methods</p> <p>Semi-structured interviews with 35 young women between eighteen and twenty nine years of age. The study was conducted in the Dublin and Galway regions of the Republic of Ireland. Young adults were recruited from General Practice (GP) practices, Third Level College health services, Family Planning clinics and specialist STI treatment services.</p> <p>Results</p> <p>Respondents were worried that their identities would become stigmatised if they accepted screening. Younger respondents and those from lower socio-economic backgrounds had the greatest stigma-related concerns. Most respondents indicated that they would accept screening if it was offered to them, however; accepting screening was seen as a correct, responsible action to engage in. Respondents wanted to be offered screening by younger female healthcare professionals. Respondents were willing to inform their current partners about positive chlamydia diagnoses, but were more ambivalent about informing their previous partners.</p> <p>Conclusions</p> <p>If an effort is not put into reducing young women's stigma-related concerns the population coverage of Chlamydia screening might be reduced.</p

Triggers of self-conscious emotions in the sexually transmitted infection testing process

<p>Abstract</p> <p>Background</p> <p>Self-conscious emotions (shame, guilt and embarrassment) are part of many individuals' experiences of seeking STI testing. These emotions can have negative impacts on individuals' interpretations of the STI testing process, their willingness to seek treatment and their willingness to inform sexual partners in light of positive STI diagnoses. Because of these impacts, researchers have called for more work to be completed on the connections between shame, guilt, embarrassment and STI testing. We examine the specific events in the STI testing process that trigger self-conscious emotions in young adults who seek STI testing; and to understand what it is about these events that triggers these emotions.</p> <p>Semi-structured interviews with 30 adults (21 women, 9 men) in the Republic of Ireland.</p> <p>Findings</p> <p>Seven specific triggers of self-conscious emotions were identified. These were: having unprotected sex, associated with the initial reason for seeking STI testing; talking to partners and peers about the intention to seek STI testing; the experience of accessing STI testing facilities and sitting in clinic waiting rooms; negative interactions with healthcare professionals; receiving a positive diagnosis of an STI; having to notify sexual partners in light of a positive STI diagnosis; and accessing healthcare settings for treatment for an STI. Self-conscious emotions were triggered in each case by a perceived threat to respondents' social identities.</p> <p>Conclusion</p> <p>There are multiple triggers of self-conscious emotions in the STI testing process, ranging from the initial decision to seek testing, right through to the experience of accessing treatment. The role of self-conscious emotions needs to be considered in each component of service design from health promotion approaches, through facility layout to the training of all professionals involved in the STI testing process.</p

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake